Azafluorene derivatives as inhibitors of SARS CoV-2 RdRp: Synthesis, physicochemical, quantum chemical, modeling and molecular docking analysis

M Venkateshan; M Muthu; J Suresh; R Ranjith Kumar

doi:10.1016/j.molstruc.2020.128741

Azafluorene derivatives as inhibitors of SARS CoV-2 RdRp: Synthesis, physicochemical, quantum chemical, modeling and molecular docking analysis

J Mol Struct. 2020 Nov 15:1220:128741. doi: 10.1016/j.molstruc.2020.128741. Epub 2020 Jun 23.

Authors

M Venkateshan¹, M Muthu², J Suresh¹, R Ranjith Kumar²

Affiliations

¹ Department of Physics, The Madura College, Madurai, 625011, Tamilnadu, India.
² Department of Organic Chemistry, Madurai Kamaraj University, Madurai, 625021, Tamilnadu, India.

Abstract

The crystal structures of 2-(1H-indol-3-yl)-4-phenyl-5H-indeno [( Cheng et al., 2007; Lee et al., 2003) 1,21,2-b]pyridine-3-carbonitrile (Ia) and 2-(1H-indol-3-yl)-4-(4-methoxyphenyl)-5H-indeno [( Cheng et al., 2007; Lee et al., 2003) 1,21,2-b]pyridine-3-carbonitrile (Ib) were determined using single crystal X-ray diffraction. Both the compounds belong to the triclinic system with the P-1 space group. The azafluorene ring system in both the compounds is effectively planar. The intermolecular interactions present in the compounds are discussed using Hirshfeld surface analysis, QTAIM and NCI. Compound Ib formed a strong interaction (-24.174 kJ/mol) with the solvent molecule. Both the compounds were geometry optimized using DFT/B3LYP level of theory. The compound's drug-like behaviors were studied using HOMO-LUMO analysis. The homology modeling of SARS CoV-2 RdRp was done utilizing the PDB 6NUR_A as a template. The model showed above 99% similarity with its preceder SARS CoV. The molecular docking analysis of the synthesized compounds was carried out along with some suggested drugs for COVID-19 and some phytochemicals. The docking results were then analyzed. The binding free energy of the complexes were calculated using MM-PB(GB)SA and ADMET properties of Ia and Ib were also predicted. Some suggestions are given from this analysis.

Keywords: ADMET; Azafluorene; Homology modeling; MM-GBSA; RdRp; SARS Coronavirus.