Recent pandemic situation of COVID-19 is caused due to SARS-CoV2 and almost all the countries of the world has been affected by this highly contagious virus. Main protease (M pro ) of this virus is a highly attractive drug target among various other enzymes due to its ability to process poly-protein that is the translated product of the SARS-CoV2 RNA. The aim of the present study demonstrates molecular docking study of Glycyrrhiza glabra (Gg) active compounds such as Glycyrrhizic acid (GA), Liquiritigenin (L) and Glabridin (G) against the M pro . Docking studies shows that these active compounds bind strongly with some of the amino acid residues in the active site of M pro and inhibits the enzyme strongly. GA, L, and G are proposed to be strong inhibitors of the enzyme and the amino acids: His 41 , Gly 143 , Gln 189 , Glu 166 , Cys 145 , Thr 25 , Asn 142 , Met 49 , Cys 44 , Thr 45 and pro 168 present in the active site of M pro were shown to make non-covalent interaction with these compounds. In silico ADMET properties prediction also shows that Gg active compounds had good solubility, absorption, permeation, non-toxic, and non- carcinogenic characteristics. Our finding concludes that all of the three active compounds of Gg could have the potential to be strong inhibitors for M pro of SARS-CoV2 but glycyrrhizic acid have a high binding affinity of -8.0 Kcal/mol and glycyrrhizic acid have good ADMET properties than the other two.

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Thiosemicarbazones are known for their biological and pharmacological activities. In this study, we have synthesized and characterized 3-Methoxybenzaldehyde thiosemicarbazone (3-MBTSc) and 4-Nitrobenzaldehyde thiosemicarbazone (4-NBTSc) using IR, 1HNMR and 13C NMR. The compound’s in vitro anticancer activities against different cell lines were evaluated. Molecular docking, Insilco ADMET, and drug-likeness prediction were also done. The test compounds showed a comparative IC50 and growth inhibition with the standard drug Doxorubicin. The IC50 ranges from 2.82 µg/mL to 14.25 µg/mL in 3-MBTSc and 2.80 µg/mL to 7.59 µg/mL in 4-NBTSc treated cells. The MTT assay result revealed, 3-MBTSc inhibits 50.42 and 50.31 percent of cell growth in B16-F0 and EAC cell lines, respectively. The gene expression showed that tumor suppressor genes such as PTEN and BRCA1 are significantly upregulated in 7.42 and 5.33 folds, and oncogenes, PKC, and RAS are downregulated −7.96 and −7.64 folds, respectively in treated cells. The molecular docking performed on the four targeted proteins (PARP, VEGFR-1, TGF-β1, and BRAFV600E) indicated that both 4-NBTSc and 3-MBTSc potentially bind to TGF-β1 with the best binding energy of −42.34 Kcal/mol and −32.13 Kcal/mol, respectively. In addition, the test compound possesses desirable ADMET and drug-likeness properties. Overall, both 3-MBTSc and 4-NBTSc have the potential to be multitargeting drug candidates for further study. Moreover, 3-MBTSc showed better activity than 4-NBTSc.

We report herein the synthesis, quantum chemical electronic structure, Hirshfeld surface and molecular docking studies of 3-anisaldehyde thiosemicarbazone (I). The compound has been characterized by NMR ( 1 H, 13 C) and IR spectroscopy. Hirshfeld surface analysis has been performed to understand the intermolecular interactions. The quantum chemical calculations show good consistency between the predicted and experimental parameters. Molecular docking studies of I with two different cancer target enzymes exhibit higher binding energy than its ortho substituted analogue.

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