Integrated computational modeling and in-silico validation of flavonoids-Alliuocide G and Alliuocide A as therapeutic agents for their multi-target potential: Combination of molecular docking, MM-GBSA, ADMET and DFT analysis

Abstract

Alliuocide class of compounds belong to flavonoids and were isolated from Allium cepa. Alliuocide are the key phytoconstituents of Allium cepa having biological activities like anticancer, antidiabetic, anti-allergic, metabolic, and inflammatory disorders, antibacterial as well as effective antioxidants against chronic diseases. However, after their isolation report, there was no further work done and a gap of about 10 years. Herein, the present study was carried out to cover the gap and to identify new lead candidates in drug discovery pipeline. Alliuocide A and G were screened against various antioxidant, antidiabetic, anticancer and antibacterial target proteins. Target based screening by molecular docking against different target receptor co-crystal structure revealed Alliuocide A as potential hit, these results were further demonstrated by MM-GBSA studies. Further optimization of both compounds was done by in silico absorption, distribution, metabolism, excretion and toxicity (ADMET) studies. Both compounds followed Lipinski's rule of five therefore safe for further in vivo studies. Finally spectral studies along with quantum descriptors were carried out by employing DFT method at 6–311 G (d,p) basis set. These quantum chemical parameters proved to be important mechanism for correlating the inhibition efficiency with molecular quatum parameters. All these studies help in designing of derivatives for better pharmacological potential.