Design, Synthesis, Crystal Structure, Biological Activity and Molecular Modeling of Novel Schiff Bases Derived from Chalcones and 5-Hydrazino-1,3-Dimethyl-4-Nitropyrazole as Anticancer Agents

Abstract

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H₂SO₄. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC₅₀ among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC₅₀. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents.

Keywords:

• Schiff bases
• chalcones
• cytotoxicity
• antitumor
• IC₅₀ values

Acknowledgments

We gratefully acknowledge the financial and research support from Chemistry Department, Hashemite University. The authors are grateful to all the co-workers whose names appeared in the references. Also, we are grateful to the Middle East University, MEU, Jordan, for the academic license of the software’s used in this research article.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Chemistry Department, Faculty of Science, the Hashemite University. The biological evaluation was funded by Al-Zaytoonah University of Jordan research funds (2022-2023/11/39)