Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
451
459
10.29228/jrp.142
1032
Development of vardenafil hydrochloride-loaded silica nanoparticles with enhanced transdermal delivery
Hussein O. AMMAR
Mina Ibrahim TADROS
Nahla M. SALAMA
Amira Mohsen GHONEIM
The aim of the present study was to develop a promising silica nanoparticle system to enhance the
transdermal delivery of vardenafil hydrochloride (VRD) for treatment of erectile dysfunction. VRD-loaded silica
nanoparticles were prepared using chitosan, polyethylene glycol and tetraethyl orthosilicate. The systems were
monitored for vesicle size, zeta potential, drug entrapment efficiency, permeation of the drug after 0.5 hour (Q<sub>0.5h</sub>) and
after 12 hours (Q12h). The utmost achieved system (VRD-SNP5) was histopathologically examined for skin irritation, and
evaluated via confocal laser scanning microscopy (CLSM). VRD-SNP5 system and an oral aqueous drug dispersion were
used to determine VRD pharmacokinetic parameters using physiologically based pharmacokinetic (PBPK) modeling.
The VRD-SNP5 system comprised spherical vesicles (440.50 nm) possessing high zeta potential (26.00 mV), promising
EE percent (71.5%), low Q0.5h (39.5±2.6%), and high Q<sub>12h</sub> (91.5±4.5%). It exhibited modest histopathologic alterations in
rat skin after a 12-hour leave-on period. CLSM revealed deep drug penetration via rat skin. Following the transdermal
application of the VRD-SNP5 system, PBPK modeling proposed the achievement of lower C<sub>max</sub> values, delayed T<sub>max</sub>
estimates, and higher AUC<sub>0-24h</sub> folds in adults (3 folds) and geriatrics (1.65 folds). It could be concluded that silica
nanoparticles could represent a potential transdermal delivery system for VRD.
https://jrespharm.com/abstract.php?id=1032
Vardenafil-1silica-2nanoparticles-3transdermal-4pharmacokinetic-5.
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
460
468
10.29228/jrp.143
1033
Evaluation of emulgel formulations contain diclofenac sodium via quality by design approach
Mohammed KALAYI
Gizem YEĞEN
Neslihan ÜSTÜNDAĞ OKUR
Buket AKSU
Emulgel is considered as emulsions, either oil-in-water or water-in-oil type, that is formed via blending
with a gelling agent. Their common usage as pharmaceutical dosage form results from the broad utilization of emulsion
systems, particularly for dermatological formulations. Quality by Design (QbD) is a scientific, holistic, risk-based,
systematic, and proactive approach that starts with predefined objectives and assertiveness on product quality,
procedure understanding, and process control. In this study, the QbD approach was implemented in the production of
emulgel containing diclofenac sodium and the goal was to build quality into the product from the inception of
formulation development. The hydrogel phase and oil phase of emulgel were prepared separately, then mixed.
Emulgels were evaluated for their macroscopic, and microscopic examination, pH, electrical conductivity measurements,
and viscosity. The optimum formulation was found by using the ANN Modelling program. According to macroscopic
evaluation the optimum emulgel was an opaque white color, and homogeneous with no phase separation or grittiness.
The viscosity of the optimum formula is 4600, pH value is 6.7, electrical conductivity is 120 μS-1, and particle diameter
was also 0,989 μm. Results showed the optimized formula has the required properties. ANN modeling technique has
been used to develop a pharmaceutical formulation via determining multivariate relations between independent
parameters and quality properties affected by these parameters. Although artificial intelligence programs are not enough
to build and develop formulations by itself, they play a significant role in formulation development.
https://jrespharm.com/abstract.php?id=1033
Emulgelquality by designartificial neural networkdiclofenac sodiumcarbopol 940optimization
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
469
482
10.29228/jrp.144
1031
Development and assessment of mitoxantrone and 4- methyl umbelliferone nanoemulsions for chemotherapeutic potential on mcf-7 cell line
Vineeta MEENA
Rajani MATHUR
Azka GULL
Neha JAIN
Dhruv KUMAR
Satyendra KUMAR RAJPUT
Swati MADAN
Every year, millions of new cases of cancer of various forms are identified, resulting in a high mortality
rate. For the management of breast cancers, chemotherapeutics such as Mitoxantrone (MTO) and 4-Methyl
Umbelliferone(4-MU), show significant cytotoxic effects. The goal of this research was to develop and characterize
nanoemulsion of MTO and 4-MU and to further assess the cytotoxic activity of this formulation against MCF-7 cell
lines using MTT assay. Aqueous microtitration technique was employed to prepare the nanoemulsion using
cinnamaldehyde as an oil phase, Tween-80 as a surfactant, and PEG-400 as a co-surfactant. The developed
nanoemulsions were characterized for droplet size, PDI, %transmittance, drug content, surface morphology, and in
vitro release. Photomicrograph of developed NE showed spherical droplets with a mean diameter of 113.2±5.3 nm
and 123.2±6.17 nm for 4-MU and MTO, respectively, and a PDI was found to be 0.254 and 0.281 for 4-MU and MTO
respectively. Approximately 78.53±4.61 % of 4-MU were released under sink conditions after 8 hours in a dissolution
study. MTO-NE and 4-MU-NE had a longer drug release profile in the in-vitro method when compared to standard
drug solutions. The cytotoxic effect of 4-MU and 4-MU-NE was assessed on the MCF-7 cell line by MTT assay and
exhibited IC50s of 3.868 mM and 1.885 Mm against MCF-7, respectively. MTO and MTO-NE had IC50s of 10.51μM
and 5.027 μM against MCF-7, respectively. The results of this study show the great potential of the prepared
nanoemulsions for breast cancer; hence it can be concluded that developed NEs of chemotherapeutics lead the way
forward for further in-vivo research.
https://jrespharm.com/abstract.php?id=1031
Mitoxantrone4-methyl umbelliferoneNanoemulsionMCF-7 cell lineMTT Assay
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
483
493
10.29228/jrp.145
1034
An in-silico approach for analysing the interplay of hepatitis b viral x protein with human adaptin protein
Prachie SHARMA
Kapila KUMAR
Kamal RAWAL
Hepatitis B virus (HBV) is the predominant cause for the liver-related malignancies worldwide. Recently,
clathrin mediated pathway has been found to assist the Hepatitis B virion in entering the host cell successfully. The role
of the viral L protein subunit (LHB) has been understood to interact with clathrin proteins during the clathrin mediated
endocytosis. The role of the viral X protein is necessitated here owing to the regulatory nature of this protein during the
pathogenesis, which however has been quite elusive. Therefore, an in-silico study has been designed to assess the
interaction possibilities between the adaptor protein Gamma 2 adaptin and the regulatory viral protein X (HBX). This
study is designed to predict the interaction between Viral HBx protein and human Gamma 2 adaptin protein of clathrin
mediated endocytic pathway during the Hepatitis B viral infection using insilico protein protein docking tools. The
protein complexes Gamma-2-Adaptin-HBx and Gamma-2-Adaptin-LHB were then docked using Cluspro, Hex and
HDock respectively. We found that Gamma-2-Adaptin-HBx binding energies using Cluspro and hex we more negative
as compared to the ones obtained for the Gamma-2-Adaptin-LHB complex. This study indicates towards the HBX viral
protein in being on of the important interactors of Gamma 2 adaptin in addition to LHB.
https://jrespharm.com/abstract.php?id=1034
Hepatitis B virusHBVViral ProteinClatherinEndocytosisHuman
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
494
501
10.29228/jrp.146
1035
Time and concentration dependent effects of different solvents on proliferation of k562, hl60, hct-116 and h929 cell lines
Asli KOC
Arzu Zeynep KARABAY
Tulin OZKAN
Zeliha BUYUKBINGOL
Fugen AKTAN
Many organic solvents are used in cell culture models to dissolve polar and non-polar chemical
compounds and drugs to test their activities. However, the solvents themselves can have cytotoxic effects on
cells. The degree of cytotoxic effect may vary according to the solvent used. The aim of this study is to determine
the time and concentration dependent effects of methanol, ethanol, dimethyl sulfoxide (DMSO), ethyl acetate
and acetone on colorectal cancer (HCT-116), chronic myeloid leukemia (K562), multiple myeloma (H929) and
acute promyelocytic leukemia (HL60) cell lines. According to our results, DMSO is the most toxic solvent and
ethyl acetate and methanol are least toxic solvents in all cells. IC50 value of Acetone is greater than 10% in K562,
HL60 and HCT-116 cells in all tested incubation times but in H929 cells IC50 value of acetone is decreased over
time. In conclusion, since most of these solvents are currently being used for treatment of cells with different
drugs and compounds in biochemical toxicology studies, it is essentially important to reveal their biochemical
and toxic effects to determine the optimum concentration to be used.
https://jrespharm.com/abstract.php?id=1035
DMSOMethanolAcetoneEthanolcytotoxicitycell cultureMTTcancer
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
502
509
10.29228/jrp.147
1036
Evaluation of bacterial contents, package labelling and antimicrobial activity of some commercial probiotic products available in local market
Zahraa Amer HASHIM
The global use of probiotic products has been increasing steadily. These products are therapeutically
intended for the prevention or treatment of various diseases. Commercial probiotic products are diverse, however no
local or international regulations are applied to control the quality of these products. Many international studies have
shown a scarcity of probiotic products that comply with the international guidelines. In Iraq, there are no previous
studies that have looked at probiotic products from this scope. Therefore, the aim of this study was to assess whether
the bacterial contents and package labels of some commercial probiotic products were correct. In addition, the study
aimed to evaluate the in vitro antimicrobial activity of the isolated probiotics. Eighteen probiotic products were
purchased from local community pharmacies within 7-month period. Bacterial contents were counted using culture and
count method. Packages’ labels were checked for contents and spelling accuracy. Antimicrobial activity was performed
using conventional well-diffusion assay. Half of the eighteen products purchased from local pharmacies, did not fulfill
the taxonomy and nomenclature of bacteria. 7 products (38.8%) demonstrated positive growth on culture media and
none of them matched the labelled bacterial counts on their packages. Of these 7 products, it has been found that the 24
h-spent culture of product-1 was the only one that demonstrated the ability to inhibit the growth of Staphylococcus aureus
in vitro. These findings necessitate the need for quality and efficacy control of these fairly expensive products. The effect
of packaging and storage on the efficacy of these commercial products should also be taken into consideration.
https://jrespharm.com/abstract.php?id=1036
Antimicrobial effectbacterial countlabel accuracyprobioticsquality controlSaccharomyces boulardii
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
510
522
10.29228/jrp.148
1037
Development of freeze-dry kits containing imatinib and different chelating agents: characterization, stability and cytotoxicity studies
Emre ÖZGENÇ
Evren GÜNDOĞDU
The current study aims to develop new freeze-dry kits containing Imatinib and different chelating agents
for breast cancer treatment and diagnosis as theranostics. Four formulations (Kit-1, Kit-2, Kit-3, and Kit-4) were
prepared, and the characterization of formulations was assessed utilizing particle size, polydispersity index, zeta
potential, fourier transform infra-red analysis, ultraviolet spectrum analysis, differential calorimetry, and
thermogravimetric analysis. They were also evaluated for stability at different storage conditions and cytotoxicity effect
on fibroblast NIH-3T3 cells. The particle size, polydispersity index, and zeta potential of developed formulations were
found to be between 6953.6 ±131.6 and 5888.3 ± 131.6 nm, 0.481 ± 0.24 and 0.319 ± 0.18, -594.5±59.6 and -477.3 ± 25.32
mV, respectively. Fourier transform infra-red analysis, ultraviolet spectrum, differential calorimetry, and
thermogravimetric analysis have proven that IMT and chelating agents formed complexes in kit formulations. Also,
they exhibited stable facility and above 90% of cell viability on fibroblast NIH-3T3 cells. By the result of our study, kit
formulations can be a favorable drug delivery system in the treatment and diagnosis of breast cancer with a non-toxic
effect on healthy cells.
https://jrespharm.com/abstract.php?id=1037
Imatinibcytotoxicitybreast cancerchelating agentstheranostic
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
523
533
10.29228/jrp.149
1038
Protective effect of aminoguanidine against acute lung injury induced by influenza А(h1n1)pdm09 (mouseadapted) virus in mice with diabetes mellitus
Andrey G. ALEKSANDROV
Tatyana N. SAVATEEVA-LYUBIMOVA
Konstantin V. SIVAK
Kira I. STOSMAN
Irina N. ZHILINSKAYA
Advanced glycation end products (AGEs) formation is a reason for protein dysfunction and inflammatory
response during acute lung injury (ALI) and diabetes mellitus (DM). Previous studies showed the efficacy of AGEs
blockers against inflammatory response and protein dysfunction. But the efficacy of AGEs blockers against ALI with
combined pathology stays unclear. This study was performed on albino female mice with DM. Virus-induced ALI was
induced by the pandemic strain of influenza virus A(H1N1)pdm09. Experimental DM was induced by a single
subcutaneous injection of alloxan monohydrate (180 mg/kg). Aminoguanidine bicarbonate (25 mg/kg, subcutaneously)
was administered during 7 days post-infection. In our research, we evaluated parameters of ALI during influenza
infection such as survival rate, blood-oxygen saturation, levels of cytokines in lung tissue, specific hematological
parameters, lung tissue morphology, and AGEs level in the lungs. The protective effect of aminoguanidine was
confirmed by reduction mortality, decreasing of hypoxia and limitation of lung damage(p<0.05). At the same time, a
reduction of inflammation response and AGEs level in the lung was observed in treated infected mice with DM (p<0.05).
Based on obtained results, aminoguanidine showed efficacy against virus-induced ALI with DM.
https://jrespharm.com/abstract.php?id=1038
advanced glycation end productsacute lung injuryaminoguanidinediabetes mellitusinfluenza
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
534
542
10.29228/jrp.150
1039
Acute hyperglycemia causes oxidative stress which is prevented by vitamin e pretreatment in healthy rabbits
KAZKAYASI Inci
TELLI Gokcen
BALCI Aylin
UMA Serdar
Although there are many studies showing chronic hyperglycemia in diabetes increases oxidative
stress, those examining the influence of acute glucose increase are limited. The aim of this study was to
investigate the effect of acute hyperglycemia on oxidative stress markers in non-treated and vitamin E pretreated
healthy rabbits. Acute hyperglycemia was induced by oral glucose administration (1g/kg). Before and at
different time points up to 180 minutes following the administration, blood samples were collected to measure
malondialdehyde and glutathione spectrophotometrically as oxidative stress and antioxidant capacity markers
respectively. Same markers were also determined in kidney and liver homogenates. There was no difference in
glucose tolerance between non-treated and vitamin E pre-treated groups (p=0.10). Plasma malondialdehyde
levels were increased after glucose administration in both groups. There was a positive-correlation between
blood glucose and plasma malondialdehyde in non-treated (r=+0.447; p=0.008) but not in vitamin E pre-treated
group (r=0.076; p=0.361). Plasma glutathione levels were higher in vitamin E pre-treated group at all-time points
compared to non-treated group (p<0.05). There was a negative-correlation between blood glucose and plasma
glutathione levels in non-treated (r=- 0.357; p=0.033) but not in vitamin E pre-treated group (r=0.007; p=0.485).
According to our results acute hyperglycemia provokes oxidative stress which is partially prevented by vitamin
E pretreatment.
https://jrespharm.com/abstract.php?id=1039
Blood glucosediabeteshyperglycemiamalondialdehydeglutathione
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
543
553
10.29228/jrp.151
1040
The role of metformin and aerobic exercise on the hepatic ischemia-reperfusion injury in streptozotocin- induced diabetic mice
Gokcen TELLI
Orcin TELLI-ATALAY
Due to prolonged hyperglycemia many of the diabetic patients suffer from complications such as liver
damage. Diabetic patients are known to have the need for liver surgeries more than non-diabetic do. The ischemia
reperfusion injuries (IRI) are one of the main complications of these surgeries and the IRI-related increase in oxidative
stress has been known to be higher in diabetic patients. Metformin and aerobic exercise are important tools being used
especially in type-2 diabetes. However, their effects and roles in liver IRI in type-1 diabetic patients are not known. This
study aimed to investigate the effects of metformin and exercise on hepatic IRI in diabetes in streptozotocin induced
type-1 diabetic mice. Diabetes was induced by streptozotocin and two weeks after the disease developed, mice were
started to treat with metformin and/or aerobic exercise during four-weeks. Blood glucose levels of the mice were
measured again and the glucose tolerance test (OGTT) was performed for each mouse. The day after OGTT, ischemia
was performed for 45 minutes in the liver and then reperfusion was provided for 5 hours. The liver of the mice was
isolated at the end of the experiments. The malondialdehyde, superoxide dismutase and nitrite levels were measured
with colorimetric analysis. Metformin reduced the insulin resistance alone and together with aerobic exercise. Oxidative
stress in the liver after IRI was diminished both with metformin and/or aerobic exercise in diabetic mice. Our study
indicated that metformin accompanied with aerobic exercise might be an important treatment strategy for preventing
the IRI in the liver of type-1 diabetic patients.
https://jrespharm.com/abstract.php?id=1040
Liver injuryischemia-reperfusionmetforminaerobic exercisetype-1 diabetes
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
554
564
10.29228/jrp.153
1041
The effect of cotinus coggygria l. ethanol extract in the treatment of burn wounds
Buşra ERTAŞ
Betül OKUYAN
Ali ŞEN
Feriha ERCAN
Hüseyin ÖNEL
Fatih GÖĞER
Göksel ŞENER
The overall aim of the present research is to evaluate for the first time the curative effect of Cotinus
coggygria leaves on burn injury in an experimental burn model along with its anti-inflammatory and antioxidant activity
potential. Also, phenolic compounds of C. coggygria were characterised by LC-MS/MS. Wistar albino rats weighing 200-
250 g were exposed to 90°C bath for 10 s to induce burn injury, involving 30% of the total body surface area. In the
treatment groups, 5% C. coggygria ethanol extract was applied topically as a cream immediately after the burn. Blood
and skin tissue samples were taken after decapitation at the 4th and 48th hours following the burn procedure. Interleukin
1-β (IL-1β) and tumour necrosis factor (TNF-α) were determined in serum samples, and hydroxyproline, prostoglandin
E2 (PGE2), and myeloperoxidase (MPO) activity and 8-hydroxy-2′-deoxy-guanosine (8-OHdG) levels were determined
in skin tissue samples. Increased levels of serum cytokines were decreased with C. coggygria treatment in both periods.
MPO activity, prostaglandine (PGE2), and 8-OhdG levels increased, while hydroxyproline levels decreased due to burn
damage. On the other hand, these parameters were returned to its normal levels with C. coggygria treatment. In addition,
the tissue histology of animals treated with C. coggygria showed a complete epithelialization with increased
collagenation. As a result, C. coggygria may be an alternative treatment approach for burns-induced skin damage and
wounds.
https://jrespharm.com/abstract.php?id=1041
Antioxidant activityanti-inflammatory activityburn wound healing activityCotinus coggygriaphenolic compounds
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
565
573
10.29228/jrp.154
1042
Antioxidant activity and nephroprotective effect of lansium parasiticum leaves in doxorubicin-induced rats
Muhammad Fauzan Lubis
Hafid Syahputra
Didi Nurhadi Illian
Vera Estefania Kaban
Doxorubicin is an important drug, especially in the treatment of cancer. But the effectiveness of its use is
inseparable from its side effects, such as nephrotoxicity. This study aimed to examine the protective effect in
doxorubicin-induced rats of Extract Ethanol of Lansium parasiticum leaves (EELP). The antioxidant activity of EELP was
identified using the DPPH method and traced the total phenol content using the Folin-Ciocalteu method and total
flavonoids using the colorimetry method. Oxidative stress and renal injury induced in doxorubicin treated rats were
proved by the significant elevation of urea and creatinine and alteration in oxidative stress markers [MDA and GSH
levels]. Histopathology of organs was examined under a microscope to see the damage that occurs in the tissue. The
measurement results of antioxidant activity showed that EELP had a strong activity with an IC50 value of 14.8±0.7
μg/mL, 107.5±0.8 μg GAEs/mg extract for phenol content, and 33.6±0.3 μg quercetin/mg extract for flavonoid content.
EELP was able to reduce MDA, urea, creatinine and increase GSH level. Observation of kidney tissues revealed a
protective effect of EELP. This was characterized by a reduction in the type of damage that occurs in the kidney tissue
of doxorubicin-induced rats. This study suggests that EELP through its antioxidant properties has a protective effect
against doxorubicin-induced nephrotoxicity.
https://jrespharm.com/abstract.php?id=1042
NephrotoxicityDoxorubicinLansium parasiticumOxidative stress
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
574
580
10.29228/jrp.155
1043
Chemical analysis and enzyme inhibitory activities of essential oil obtained from allium proponticum subsp. proponticum, an endemic species
Ceren EMİR
Ahmet EMİR
Allium species belong to the Amaryllidaceae family and are represented with approximately 900 species,
with 220 taxa found in Turkey. The aim of the present study is to analyze the chemical structure and to investigate the
enzyme inhibitory activities linked to Alzheimer's Disease, skin disorders, and type 2 Diabetes Mellitus of essential oil
obtained from Allium proponticum subsp. proponticum, which is an endemic species. The essential oil was obtained with
hydrodistillation using a Clevenger-type apparatus from flower parts of the plant and the analysis was carried out by
Gas Chromatography Mass Spectrometry. Inhibitory activities of samples against acetylcholinesterase,
butyrylcholinesterase, tyrosinase, α-amylase, and α-glucosidase were realized in a 96-well microplate using an ELISA
microplate reader. The yield of essential oils was 0.0095 %. A total of 17 components, 11 of sulfur-containing compounds
(73.83 %), were identified, constituting 86.72 % of the total essential oil. IC50 values of enzymes inhibitory activities were
258.47 ± 3.28 for acetylcholinesterase, 522.81 ± 1.29 for butyrylcholinesterase, 38.22 ± 1.87 for tyrosinase, 28.50 ± 1.12 for
α-glucosidase and 14.68 ± 0.78 for α-amylase. To conclude, the essential oil of Allium proponticum subsp. proponticum
with its sulfur-containing compounds may be a promising natural product due to its activity in inhibition of tyrosinase,
α-amylase, α-glucosidase.
https://jrespharm.com/abstract.php?id=1043
Alliumessential oilanticholinesteraseantityrosinaseantidiabetic
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
581
597
10.29228/jrp.156
1044
Formulation of a natural nanosystem based on β- cyclodextrin/arginine/xanthan to increase antifungal activity of salvia officinalis essential oil from algeria (bejaïa, kalaa n'ath abas)
Yacine NAIT BACHIR
Naima SAHRAOUI
Zahia CHEURFA
Meriem MEDJKANE
Amel HADJ ZIANE
The aim of this work is to study for the first time the chemical composition of Salvia officinalis essential oil
from Algerian region of Kabylia (Kalaa n'Ath Abas) and to evaluate its antifungal activity. The originality of this work
consists in the development of a new nanosystem based on natural excipients (β-cyclodextrin, xanthan gum and
arginine) to increase its antifungal activity. The yield of Salvia officinalis essential oil was 2.07%, it is mainly composed
of α-Thujone (23.21%), 1,8-Cineole (14.17%) and Camphor (11.02%). Nanoemulsion based on β-cyxlodextrins has an
average diameter of 219.1±5.2 nm, a zeta potential of 36.2±4.8 mV and a viscosity of 0.87±0.03 Pa.s. This essential oil
showed a good antifungal activity against all tested strains (Candida albicans, Microsporum canis and Trichophyton
equinum). Moreover, a significant increase of this activity was noted after essential oil nano-emulsification. The easy
penetration of nanodroplets composing the prepared system through fungal cell wall and their high solubility in fungal
cell cytoplasm permit to increase antifungal activity of studied essential oil.
https://jrespharm.com/abstract.php?id=1044
Salvia officinalis, essential oil, chemical composition, antifungal activity, cyclodextrins, fungicidal effect enhancement
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
598
608
10.29228/jrp.157
1045
Antioxidant, anticancer activities, and hplc-dad analyses of the medicinal halophyte limoniastrum guyonianum dur. extracts
Sara ZERROUKI
Samia MEZHOUD
Ayse SAHİN YAĞLIOĞLU
Chawki BENSOUICI
Mehmet NURİ ATALAR
Ibrahim DEMİRTAS
Souad AMEDDAH
Ratiba MEKKIOU
Although notable medicinal value and biological activities such as antioxidant, antibacterial, antimicrobial
and antifungal of Limoniastrum guyonianum have been reported, identification and quantification of phytoconstituents
of CHCl3, EtOAC, and n-BuOH extracts from the aerial parts of the halophyte medicinal plant from Algerian Sahara
was not well investigated for biological and anticancer activity in spite of their great interest. Therefore, the aim of this
study was to investigate the antioxidant and anticancer activities of L. guyonianum. The phytoconstituents of CHCl3,
EtOAC, and n-BuOH extracts were screened using HPLC-DAD. Total phenolic and flavonoid contents were quantified,
antioxidant activity, using DPPH radical scavenging activity, ABTS+° decolorization, cupric reducing power, and anticancer
activity against human cervical adenocarcinoma (HeLa) cell line were investigated and quantified. The results
showed the presence of chlorogenic, gallic, syringic, p-coumaric, trans ferulic, o-coumaric acids, and quercetin in
significant varying quantities. Chlorogenic acid was present in the greatest quantity (344.027–422.711mg/g of extract)
as well as quercetin in CHCl3 extract. It is important to note the absence of caffeic acid and o-coumaric acid from EtOAc
and CHCl3 extracts, respectively. The content of phenolic and flavonoid were higher in EtOAc extract (934±4,38mgGAE
and 218.33±6.36mgQE/gof extract), respectively. EtOAc extract possesses a strong antioxidant effect in vitro, while the
CHCl3 extract proved to be the most active againstHeLa cell lines (IC50= 50.369±0.020μg/ml). The findings in this
studydemostrate the potential use of these compounds in medicine and importance of this species, which have largely
been used in folk medicine for several diseases’ treatment.
https://jrespharm.com/abstract.php?id=1045
Limoniastrum guyonianumHPLC-DADchemical compositionanticancer activityantioxidant activity
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
609
616
10.29228/jrp.158
1046
Simultaneous determination of paracetamol and lidocaine hydrochloride in detamol injection using rp-hplc
Ayisha SHAUKAT
Khalid HUSSAIN
Nadeem Irfan BUKHARI
Naureen SHEHZADI
https://jrespharm.com/abstract.php?id=1046
Simultaneous determinationparacetamollidocaine HClvalidationquantificationderivitizationninhydrin
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
617
624
10.29228/jrp.159
1047
A hybrid ligand and structure-based virtual screening of nci compound library identifies potential sapt1 inhibitors
Suat SARI
Nisha VALAND
Umakhanth Venkatraman GIRIJA
Secretory aspartate proteases (SAPs) is a key virulence factor of Candida spp. enabling adherence to and
invasion of host tissues through breakdown of host proteins related to immunological and structural defenses, making
them potential drug targets for drug-resistant mycoses, especially where the available therapies fail. To date, no SAP
inhibitors for Candida tropicalis, one of the top five most common species isolated in Candida-related mycoses, has been
reported. In this study, we report first-time identification of a set of potential C. tropicalis SAP1 (SAPT1) inhibitors
through a hybrid ligand-and structure-based virtual screening of National Cancer Institute (NCI) library compounds.
The NCI library was refined by filtering off non-druglike molecules. Referring to a known C. albicans SAP inhibitor, a
similarity search was performed for the refined library, in addition to a pharmacophore screen using a model of the
ligand-receptor interactions between a peptide substrate and SAPT1 obtained from crystallographic data. The
compounds selected from these screens were subject to molecular docking to the SAPT1 active site and the top-scoring
ligand-receptor complexes were further included in MM-GBSA calculations to optimize the predicted binding affinities.
Finally, the selected 16 compounds, which were confirmed to make key interactions with the catalytic residues, were in
silico evaluated and found eligible for certain pharmacokinetic properties. As a future prospect, obtaining these virtual
hits and testing them in vitro against SAPT1 could validate the virtual screening process and yield the first smallmolecule
inhibitors of SAPT.
https://jrespharm.com/abstract.php?id=1047
secretory aspartate proteaseCandida tropicalisvirtual screeningshape screeningpharmacophore modelingmolecular dockingMM-GBSA
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
625
640
10.29228/jrp.160
1048
Novel pyrazole substituted oxazole derivatives: design, insilico studies, synthesis & biological activities
Srilakshmi SINGAGARI
Raja SUNDARARAJAN
A potent antibacterial drug was developed by synthesizing a set of new pyrazoles substituted oxazole
derivatives using multi-step synthesis. FT-IR, 1H-NMR, Mass spectroscopy, and bases of microanalyses are employed
to confirm the structure of compounds. Molinspiration online tool was used to predict the molecular properties and
molecular docking was used to predict the antitubercular potency of the target compounds. 10-Fold serial dilution
method, agar streak dilution test, and DPPH radical scavenging methods are utilized to evaluate antitubercular,
antibacterial, and radical scavenging properties of test compounds and reference drugs, respectively. Varying degree
of antitubercular, antibacterial, and radical scavenging activities (mild to good) was displayed by synthesized oxazole
compounds. In general, unsubstituted oxazole derivatives exhibited superior antibacterial potency than substituted
analogs. In addition, meta-substituted analogs displayed higher activity than the corresponding para-substituted
analogs. Among fifteen tested target compounds, the potent compound of this series was found to be 4-(4-(5-phenyl-
4,5-dihydro-1H-pyrazol-3-yl)benzylidene)-2-methyloxazol-5(4H)-one (PBO8). Hence, this analog may be used as a lead
molecule to find potent & safer antibacterial agents.
https://jrespharm.com/abstract.php?id=1048
OxazolePyrazoleAntitubercular activityAntibacterial activityAntioxidant activity
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
641
654
10.29228/jrp.161
1049
Synthesis, characterization and antimicrobial evaluation of new 2-(2-thienylcarbonyl)hydrazono-3-alkyl/aryl-4-thiazolidinone and 2-aryl-3-(2-thienylcarbonyl)amino-4-thiazolidinone derivatives
Efe Doğukan DİNCEL
Dilek ŞATANA
Süheyla ÖZBEY
Nuray ULUSOY-GÜZELDEMİRCİ
A series of novel 2-(2-thienylcarbonyl)hydrazono-3-alkyl/aryl-4-thiazolidinone (2a-f), 2-(2-thienyl)-5-[(4-
bromophenyl)amino]-1,3,4-oxadiazole (3), 2-aryl-3-(2-thienylcarbonyl)amino-4-thiazolidinone (5a-h) and 2-aryl-3-(2-
thienylcarbonyl)amino-5-methyl-4-thiazolidinone (6a-h) were designed and synthesized. The structural elucidations of
the novel compounds were performed by IR, 1H-NMR, mass and elemental analysis. The compounds were evaluated
for their antimycobacterial and antifungal activities. According to the biological activity studies activities of the
compounds, 2f (MIC: >12.5 μg/ml, 76% inhibition), 3 (MIC: >12.5 μg/ml, 43% inhibition), and 5c (MIC: >12.5 μg/ml,
38% inhibition), displayed antimycobacterial activity. 2b (MIC: 25 μg/ml) displayed antifungal activity against T.
rubrum. Besides, x-ray crystallography studies were performed to illuminate the structure of 2e. Consequently, the
obtained results relvealed that 2f, 3 and 5c present a leading structure for future drug development due to its
straightforward synthesis and relevant bioactivity.
https://jrespharm.com/abstract.php?id=1049
4-Thiazolidinonesoxadiazolecrystal structureantimycobacterial activityantifungal activity
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
655
662
10.29228/jrp.162
1050
Liquid chromatographic determination of pk<sub>a</sub> value of 1- (2-methylbenzonitrile)-3-benzylbenzimidazolium bromide as a drug candidate in acetonitrile-water binary mixtures
İlkay KONÇE
Senem AKKOÇ
Zehra ÜSTÜN
Ebru ÇUBUK DEMİRALAY
The ionization/protonation (pK<sub>a</sub>) constant, which is a physicochemical parameter that directly affects the
pharmacokinetic properties of a drug such as absorption, distribution, metabolism, and excretion (ADME), is currently
determined by analytical methods. The effect of pH of the mobile phase on the chromatographic behavior of 1-(2-
methylbenzonitrile)-3-benzylbenzimidazolium bromide (2) which its synthesis, fully characterization, and
antiproliferative activity properties were studied previously, and the protonation constant (pK<sub>a</sub>) value were determined
in this study. The pKa value of compound 2, benzimidazolium salt, was determined by the reverse-phase liquid
chromatographic (RPLC) method at 25 ºC. sspK<sub>a</sub> values were evaluated using retention time (t<sub>R</sub>) in acetonitrile-water
binary mixtures with acetonitrile (ACN) percentages of 40%, 45%, 50% and 55% (v/v). The aqueous pK<sub>a</sub> wwpK<sub>a</sub> value
of the synthesized compound was calculated from the sspK<sub>a</sub> value using the macroscopic parameters (dielectric constant
and mole fraction) which play an important role in the solvent properties. Obtained wwpK<sub>a</sub> values were found to be 11.290
and 11.241, respectively. In addition, the degree of ionization of the related compound was calculated using the wwpK<sub>a</sub> values.
https://jrespharm.com/abstract.php?id=1050
Benzimidazolium salthydro-organic mixturepKa valuemacroscopic parameter
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
663
674
10.29228/jrp.163
1051
Simultaneous determination of flurbiprofen and thiocolchicoside in pharmaceutical preparations by a validated hplc method
HAJER ASWAISSI
EBRU TÜRKÖZ ACAR
In this study, a new high performance liquid chromatography (HPLC) analysis method was developed
for the simultaneous determination of flurbiprofen (F) and thiocolchicoside (T) in pharmaceutical products. A C18
column (Agilent Poroshell 120 EC-C18) was used as the stationary phase. Elution of the analytes was achieved by using
gradient elution system. Mobile phase A was an acetate buffer (100 mM, pH 4.8) and mobile phase B was acetonitrile.
The flow rate for the method developed was 0.5 ml/min. The temperature of the column compartment was set at 40°C
and the injection volume was 5 μl. Monitoring of the analytes was carried out at 248 nm. The method was found linear
in the concentration range between 5-100 ppm. The correlation coefficient value was calculated as 0.999 for F and 0.999
for T. The method was found suitable in terms of accuracy, precision, specificity, linearity, and robustness ruggedness.
Furthermore, it was applied successfully for the analysis of commercial tablets and gel samples that contains F and T
without any time-consuming pre-procedure. The recovery values for Fand T were found as 99.5% and 97.0% in tablet
formulations and 98.6% and 99.3% in gel formulations, respectively. All results were acceptable and this confirmed that
the method is suitable for its intended use in routine quality control and an assay of drugs.
https://jrespharm.com/abstract.php?id=1051
Flurbiprofen, Thiocolchicosoide, HPLC, analysis, validation, commercial dosage forms
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
675
686
10.29228/jrp.165
1052
The effects of n(1)-2,4-dihydroxybenzylidene-n-(4) hydroxybenzylidene-s-methyl-thiosemicarbazidatooxovanadium( iv) on testicular damage in streptozotocininduced diabetic rats
Sevim TUNALI
Tulay BAL-DEMIRCI
Bahri ÜLKÜSEVEN
Refiye YANARDAG
Diabetes mellitus (DM) is a serious metabolic disorder that has negative effects on male sexual and
reproductive functions in humans and animals. The purpose of current research is to demonstrate the effect of N(1)-2,4-
dihydroxybenzylidene-N(4)-2-hydroxybenzylidene-S-methyl-thiosemicarbazidato-oxovanadium(IV) (VOL) on testicular
damage in male rats with streptozotocin (STZ)-induced diabetes. Male Swiss albino rats were randomly grouped as
follows: Control (intact) group animals; control group animals given VOL (0.2 mM/kg/day) for 12 days; STZ-induced
diabetic animals; diabetic animals given VOL group, at same dose and time. Experimental diabetes was induced with a
single dose of 65 mg/kg intraperitoneal STZ injection. On day 12, overnight fasted animals were sacrificed and testis
tissues (right and left) were collected and homogenized in 0.9 % saline. After centrifugation, protein levels and nonenzymatic
parameters such as glutathione, lipid peroxidation, protein carbonyl, as well as the activities of alkaline
phosphatase, myeloperoxidase and enzymatic antioxidants were determined. Based on the results obtained, VOL was
shown to be a potentially beneficial compound in the amelioration of damaged testicular tissue of male diabetic rats after
12 days of administration. Our results suggest that VOL may be a promising candidate for the development of new
generation antidiabetic drugs, and its administration to diabetic rats may be a suitable candidate in reducing testicular
damage.
https://jrespharm.com/abstract.php?id=1052
Diabetes mellitusoxovanadium complextesticular damageoxidative stress
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
687
696
10.29228/jrp.166
1053
Evaluation of clinical pharmacist interventions on drugrelated problems in the gastroenterology ward
Cengizhan CEYLAN
Mesut SANCAR
Ayfer BECEREN
Ali DEMİR
Coşkun KUŞ
Gülden Zehra OMURTAG
Integrating clinical pharmacists in a multidisciplinary patient care team improves the treatment process
by identifying and resolving drug-related problems (DRPs). The aim of the study was to determine the effect of clinical
pharmacist intervention for DRPs in the gastroenterology service. The first period of the study was conducted between
15.06.2018 and 15.02.2019. Eighty patients admitted to the gastroenterology ward, who used at least one medication,
were included in ‘the study group’. The clinical pharmacist participated in ward rounds and made interventions to
solve identified DRPs. In the second period of the study, the control group consisted of 80 patients admitted to the same
ward between 01.03.2019 and 06.06.2019. DRPs were determined only from the data obtained from the hospital system
in the control group. DRPs were classified according to the European Pharmaceutical Care Network (PCNE V9.1). A
total of 136 and 46 with an average of 1.7 and 0.57 DRPs per patient (p≤0.01) were identified in the study and control
groups, respectively. Of the DRPs in the study group, 59 were related to treatment effectiveness, while 61 were related
to treatment safety. Likewise, 21 DRPs were related to treatment effectiveness in the control group, while 12 were related
to treatment (p≤0.01). 65% of the interventions were made at the physician level and 49% at the drug level. 97% (n=133)
of the total interventions were accepted. The number of DRPs was significantly reduced in the control group within the
time frame after the clinical pharmacist intervention period. In conclusion, clinical pharmacists' importance in detecting
and preventing DRPs in the gastroenterology ward has been demonstrated.
https://jrespharm.com/abstract.php?id=1053
Clinical pharmacistdrug-related problemsgastroenterologymedication review
Marmara Üniversitesi
Journal of Research in Pharmacy
2630-6344
2022
26
3
697
703
10.29228/jrp.167
1054
A sensitive surfactant-mediated spectrofluorimetric determination of chemotherapeutic agent topotecan in human serum and its investigation of dna binding mechanism
Engin ER
An overdose of an anticancer agent in the human body not only leads the high cytotoxicity on the
neoplastic cells but also causes serious side effects. The regular detection of an anticancer agent level in biological fluids
using an alternative technique is crucial in terms of assessment of therapeutic efficiency in chemotherapy process. In
this work, we developed a micelle-enhanced spectrofluorimetric approach for the determination of topotecan (TPC),
which is an effective anticancer agent used in the treatment of certain types of cancer, in human serum and binding
mechanism of TPC-DNA. The proposed method exhibited a strong pH-dependent emission signal at 535 nm after
excitation of 380 nm towards the TPC in the presence of surfactants. The relative fluorescence signal for TPC was found
to be linear in the wide concentration range of 0.01 – 1.8 μM (R2 = 0.9981) with a challenging detection limit of 3.3 nM.
The developed spectrofluorimetric method was successfully applied to the analysis of TPC in spiked human serum
samples with the good recovery results. Moreover, for the first time, the interaction mechanism between TPC and
double-stranded DNA (ds-DNA) was studied by developed spectrofluorimetric method. The binding constant value of
8.5 x 10-3 M-1 calculated by Stern-Volmer method indicated the strong intercalation-based binding of TPC into the base
pair of ds-DNA. The developed spectrofluorimetric method can provide new insight for the design of DNA-targeted
drugs, and lead an alternative approach for the detection of anticancer drugs such as TPC in biological samples.
https://jrespharm.com/abstract.php?id=1054
SpectrofluorimetryDrug–DNA interactionFluorescenceIntercalationDetermination