Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors


ŞENKARDEŞ S., HAN M. İ. , KULABAŞ N., ABBAK M., ÇEVİK Ö., KÜÇÜKGÜZEL İ., ...More

MOLECULAR DIVERSITY, vol.24, no.3, pp.673-689, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 24 Issue: 3
  • Publication Date: 2020
  • Doi Number: 10.1007/s11030-019-09974-z
  • Title of Journal : MOLECULAR DIVERSITY
  • Page Numbers: pp.673-689

Abstract

In trying to develop new anticancer agents, a series of sulfonylhydrazones were synthesized. All synthesized compounds were checked for identity and purity using elemental analysis, TLC and HPLC and were characterized by their melting points, FT-IR and NMR spectral data. All synthesized compounds were evaluated for their cytotoxic activity against prostate cancer (PC3), breast cancer (MCF-7) and L929 mouse fibroblast cell lines. Among them,N '-[(2-chloro-3-methoxyphenyl)methylidene]-4-methylbenzenesulfonohydrazide(3k)showed the most potent anticancer activity against both cancer cells with good selectivity (IC50 = 1.38 mu M on PC3 with SI = 432.30 and IC50 = 46.09 mu M on MCF-7 with SI = 12.94). Further investigation confirmed that3kdisplayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound3kwas identified as the most potent COX-2 inhibitor (91% inhibition) beside lower COX-1 inhibition. Molecular docking of the tested compounds represented important binding modes which may be responsible for their anticancer activity via inhibition of the COX-2 enzyme. Overall, the lead compound3kdeserves further development as a potential anticancer agent.