Synthesis, molecular docking and evaluation of novel sulfonyl hydrazones as anticancer agents and COX-2 inhibitors
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 μM on PC3 with SI = 432.30 and IC50 = 46.09 μM on MCF-7 with SI = 12.94). Further investigation confirmed that 3k displayed morphological alterations in PC3 and MCF-7 cells and promoted apoptosis through down-regulation of the Bcl-2 and upregulation of Bax expression. Additionally, compound 3k was 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 compound 3k deserves further development as a potential anticancer agent.
KeywordsAnticancer activity Apoptosis Cyclooxygenase Molecular docking Sulfonylhydrazones
This work was supported by the Research Fund of Marmara University, Project Number: SAG-K-120917-0495.
Compliance with ethical standards
Conflict of interest
The authors have declared no conflict of interest.
- 10.Gupta S, Srivastava M, Ahmad N et al (2000) Over-expression of cyclooxygenase-2 in human prostate adenocarcinoma. Prostate 42:73–78. https://doi.org/10.1002/(SICI)1097-0045(20000101)42:1%3c73:AID-PROS9%3e3.0.CO;2-G CrossRefGoogle Scholar
- 36.Morrow D, Daniel R, Dubois N (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58:362–366Google Scholar