Synthesis, Characterization, Anticancer, Pharmacokinetic, and Docking Studies of Vanillin-Benzimidazole Derivatives as Aromatase Inhibitors

Abstract

The current work highlights the preparation and antitumor activity of new benzimidazole derivatives of the natural product vanillin as a novel aromatase inhibitor. All the newly reported hybrids were characterized using sophisticated analytical techniques like NMR, IR, and mass spectrometry. The anticancer results against five cancer cell lines exhibited compounds 6, 7, and 8 to be most sensitive with IC₅₀ in the range 0.36–8.65 μM, whereas doxorubicin showed IC₅₀ of 4.74 μM and 3.69 μM toward breast cancer cells, MCF-7 and MDA-MB-231, respectively. Also, compound 6 revealed promising aromatase inhibition with IC₅₀ 0.064 μM while 7 and 8 with IC₅₀ 1.16 and 2.87 μM, respectively. Compound 9-bearing morpholine heterocycle revealed a better antibacterial effect on S. aureus with 22 mm (ZI) and MIC of 25 µg/disk than amoxicillin. These synthesized compounds displayed desirable pharmacokinetic properties and interacted with active sites of the aromatase enzyme in docking study. In conclusion, compound 6 was found to be a promising molecule as an aromatase inhibitor for breast cancer therapy.