Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2022 , Vol 26 , Issue 1
Synthesis of some novel hydrazide-hydrazones derived from etodolac as potential anti-prostate cancer agents
Hande Cevher KOÇ1,İrem ATLIHAN2,Pınar MEGA-TİBER3,Oya ORUN3,Ş. Güniz KÜÇÜKGÜZEL4
1Department of Pharmaceutical Chemistry, Institute of Health Sciences, Marmara University, İstanbul, Turkey
2Department of Biophysics, Institute of Health Sciences, Marmara University, İstanbul, Turkey
3Department of Biophysics, Faculty of Medicine, Marmara University, İstanbul, Turkey
4Vocational School of Health Services, Fenerbahçe University, İstanbul, Turkey
DOI : 10.29228/jrp.97 (R,S)-Etodolac [1,8-diethyl-1,3,4,9-tetrahydrapyrano(3,4-b)indole-1-acetic acid] is a nonsteroidal anti-inflammatory drug that contains carboxylic acid group with the structure of pyrano[3,4-b]indole. In this study, a series of novel (R,S)-Etodolac derivatives (3a-l) bearing hydrazide-hydrazone moiety were synthesized. The structures of these compounds were characterized by spectral (1H-NMR and FT-IR analyses) methods. All synthesized compounds were screened for anticancer activity against androgen-independent prostate adenocarcinoma (PC-3, DU-145) and androgen-dependent prostate adenocarcinoma (LNCaP) cell lines by using WST-8 colorimetric method. This method was used for cell viability and cytotoxicity analysis. Compound 3b (SGK-720) [2-(1,8-diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(2,6-dichlorophenyl)methylene]hydrazides] showed 10.36, 5.24, 15.53 μM anticancer activity against PC3, DU145, LNCaP cancer cell lines, respectively. According to JC-1 mitochondrial membrane potential test and Annexin V/PI staining, 3b was found to have apoptotic effect on these cancer cells. It is concluded that compound 3b containing 2,6-dichloro substituents may be one of the candidate molecules to cope with prostate cancer. Keywords : Etodolac; hydrazide-hydrazone; anticancer activity; apoptosis; WST-8 colorimetric method
Marmara University