Synthesis and anticancer activity against prostate cancer of hydrazide-hydrazones derived from etodolac
Hande Cevher Koç, İrem Atlıhan, Pınar Mega Tiber, Oya Orun, Ş. Güniz Küçükgüzel
Abstract
R,S)-Etodolac [1,8-diethyl-1,3,4,9-tetrahydrapyrano(3,4-b)indole-1-acetic acid] is a nonsteroidal antiinflammatory 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 ( 1 H-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-1,3,4,9tetrahydropyrano[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.