Structure activity evaluation and computational analysis identify potent, novel 3-benzylidene chroman-4-one analogs...

3-Benzylidene chroman-4-ones share close homology with naturally occurring bioactive compounds.

This study evaluated the antifungal, antioxidant, and anticancer activities of novel 3-benzylidene chromanone analogs with respect to their structure-activity relationships.

Compounds 45e-64e were synthesized inhouse. Aspergillus niger (MTCC 1344) Aspergillus flavus and Botrytis cinerea were the fungal strains tested. Computational docking analysis was carried out for vanin-1, estrogen receptor (ER), and Akt proteins using Auto-dock vina. Free radical scavenging and total antioxidant capacity was analyzed using spectrophotometric methods. MCF-7 (breast cancer) cell line was used for anticancer assays. Flow cytometry was used to detect cell cycle and apoptosis.

Out of the twenty compounds screened, compounds 47e, 50e, 52e, 57e, and 61e that possessed either methoxy and ethoxy/methyl/isopropyl group exhibited very good activity against all fungi. Compounds possessing methoxy group alone showed moderate activity and compounds devoid of methoxy, and ethoxy groups did not show any activity. When computationally analyzed against target proteins for antioxidant properties, the compounds exhibited excellent binging efficacy to vanin-1 and ERs. These predictions were translated in the in vitro free-radical scavenging and antioxidant assays. The compounds exhibited anti-proliferative efficacy in breast cancer cell line, increased the sub-G₀/G₁ cell cycle populations and total apoptosis in MCF-7 cells. Additionally, the compounds also depicted excelling binging energy when computationally analyzed for Akt enzyme binding.

In summary, our study identified potential analogs of 3-benzylidene chroman-4-one molecules with excellent anti-fungal, anti-oxidant, and anticancer activities which demand further research for drug developments.