Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies of Novel Pyrrole Derivatives of Khellin and Visnagin via One-Pot Condensation Reaction with Curcumin

Novel pyrrole derivatives were synthesized by one-pot four components condensation reaction of khellin and/or visnagin carbaldehyde; amine derivatives; curcumin and nitro methane. In another approach with lack of curcumin molecular structure, new pyrrole derivatives were efficiently achieved using ethyl acetoacetate. Newly synthesized compounds were tested against human pancreas cancer cell lines (Panc-1), colon cancer cell line and (MCF-7), (HT-29) breast cancer cell line. The results showed that newly synthesized compounds exhibit a moderate to strong growth inhibition of breast cancer cell line MCF-7 in comparison to the other two cell lines. Compounds which are combination between both Curcumin and khelline derivatives showed highest activity towards human breast cancer cell line (MCF-7). Molecular docking studies declared that these compounds occupied a pocket of “EGFR tyrosine kinase” (WT) and a pocket of “EGFAR Kinase domain PCSK9-∆C D374Y” (MT). In addition, our compounds are non-inhibitors of CYP2D6, which means that liver dysfunction effects are not expected. All newly synthesized strucrures are consistent with biological results and predicted to be safe.