Synthesis, docking and biological evaluation of 2,4-disubstituted quinazolines with multi-target activities as anti-cancer and antimicrobial agents

Abstract

A series of 2,4-disubstituted quinazoline derivatives was designed and synthesized as multi-target therapeutic agents that may act as anti-cancer and antimicrobial agents. The target compounds were evaluated for primary anti-cancer activity followed by EGFR inhibition assay for most potent compounds. Compounds 6 and 8c exhibited good EGFR inhibition activity with IC50 values of 0.201 and 0.405 μM, respectively, in comparison to lapatinib as a reference with IC50 value of 0.115 μM. Docking study of the synthesized compounds into the binding site of EGFR tyrosine kinase was performed to compare the binding mode of these compounds to the known EGFR inhibitor, lapatinib. Moreover, antimicrobial activity, cytotoxity and hemolytic analysis were estimated according to CO-ADD (The Community for Antimicrobial Drug Discovery) procedures. Compounds 4 and 5c possessed potent antifungal activity with minimum inhibitory concentration (MIC) values of 8 and 4 μg/mL against C. albicans and C. neoformance, respectively, compared to fluconazole as a reference drug with MIC values of 0.125 and 8 μg/mL against same fungi.