Synthesis of some novel hydrazide-hydrazones derived from etodolac as potential anti-prostate cancer agents

Koc H. C., Atlıhan İ., Mega Tiber P., Orun O., Kucukguzel S. G.

JOURNAL OF RESEARCH IN PHARMACY, cilt.26, sa.1, ss.1-12, 2022 (ESCI) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 26 Sayı: 1
  • Basım Tarihi: 2022
  • Doi Numarası: 10.29228/jrp.97
  • Dergi Adı: JOURNAL OF RESEARCH IN PHARMACY
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), Scopus, TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.1-12
  • Anahtar Kelimeler: Etodolac, hydrazide-hydrazone, anticancer activity, apoptosis, WST-8 colorimetric method, IN-VITRO, ANTICANCER, APOPTOSIS, DERIVATIVES, INHIBITOR, NS5B, HCV
  • Marmara Üniversitesi Adresli: Evet

Özet

(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-h]indole. In this study, a series of novel (R,S)-Etodolac derivatives (3a-1) bearing hydrazide-hydrazone moiety were synthesized. The structures of these compounds were characterized by spectral (H-1-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 mu M 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.