WELPSA: A Green Catalyst Mediated Microwave Assisted Efficient Synthesis of Novel 5-Aminopyrazole-4-Carbonitrile Derivatives as Anticancer Agents (MCF-7, A-549) and In Silico Studies

Abstract

Malononitrile, modified hydrazine, and quinoline aldehyde were combined in a one-pot reaction under microwave irradiation to create the medicinally significant family of heterocyclic scaffolds, quinoline, coumarin, thiazole, and pyrazole 4-carbonitrile derivatives with the help of green solvent as water. WELPSA (water extract of lemon peel-soaked ash) is used to speed up the reaction in a solvent-free environment, according to more environmentally friendly reaction protocols. This methodology offers several advantages like short reaction duration, green solvent synthesis, high yield, no need for chromatographic techniques, catalyst recyclability of up to five cycles, and so on. Synthesized derivatives were evaluated for anticancer potential against lung (A549) and breast cancer cell lines. Among the tested compounds, 4i and 4j exhibited remarkable anticancer activities. Further investigations using Annexin V staining and flow cytometry revealed that both compounds effectively induced apoptosis in A549 cancer cells. Compound 4i was subjected to molecular docking and dynamic studies to understand the molecular basis of their activity, which demonstrated a strong interaction with the target protein 1m17, providing insights into its mechanism of action. These findings highlight the potential of compounds 4i and 4j as promising candidates for anticancer drug development.