In Vitro and In Silico Evaluation of the Anticancer and Antiparasitic Activities of New 2-Methoxy Azachalconium Bromides

Abstract

Three new N-alkylpyridinium-based 2-methoxy chalcones with long, fatty alkyl chains were prepared and tested for their anticancer and antiparasitic activities. The N-octadecyl derivative (2c) displayed considerable activity against and selectivity for BRAF-mutant HT-29 colorectal carcinoma cells. Increased mRNA expression of caspases and apoptosis induction was found. In addition, expression of MEKs and ERKs was upregulated. EGFR inhibition was identified as mechanism of action for this compound further supported by in silico molecular docking studies, which revealed a binding energy of −9.19 kcal/mol against EGFR. Additionally, a strong binding affinity for VEGFR-2 was observed with a binding energy of −11.01 kcal/mol. The development of the described chalcone as anticancer drug appears to be promising. In addition, all three tested chalcone derivatives exhibited significant activities against Toxoplasma gondii and Leishmania major parasites, albeit without selectivity. Thus, the present study describes for the first time the kinase-inhibitory, anti-leishmanial, and anti-toxoplasmal activities of N-alkyl azachalconium compounds.