Abstract

K. R. Jayanthi, K. Hemapriya and Subban Ravi^*

DOI : http://dx.doi.org/10.13005/ojc/380120

In an attempt to challenge COVID-19, molecular docking of cinnamoylated chloroquine compounds 1 – 15 against main protease (Mpro) enzyme of SARS-CoV-2 was undertaken. To study the stability of the complex formed between the drug and the receptor, suitable docking possesses were selected and put into molecular dynamics studies. Further ADME properties were determined using SWISS ADME software. In the docking studies compounds 5, 9, 14 and 15 exhibited encouragable binding with the Mpro crystal structure with docking scores of -8.1, -7.9, -7.8 and -7.9 Kcal/mole respectively. It was observed that CYS145 and GLU166 played a significant role during the interaction of molecules with the active site of COVID-19 Mpro. Among compounds 5, 9, 14 and 15, compound 5 had stable interactions with the protein, which might be the reason for the optimum RMSD, RMSF, radius of gyration and protein–ligand contacts (hydrogen bonding) values. The compound 5 was synthesised and tested for its cytotoxic activity against fibroblast L929 cell line. The above study indicated that the compound 5as a promising agent, and during the drug discovery process it could be taken as a starting point for lead optimization.

ADME properties; COVID-19; cytotoxic activity; Docking studies; SARS-CoV-2

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