The DFT based spectral investigations and bioactivity of amprenavir

Autor: R. G. Abhilash Kumar, D. E. Nimmi, Partibha Sindhu, Geethu Sudhi, S.P. Chandini Sam, S. G. Praveen, Dhanesh Thomas, J. Binoy
Rok vydání: 2020
Předmět:
Zdroj: Materials Today: Proceedings. 27:188-197
ISSN: 2214-7853
DOI: 10.1016/j.matpr.2019.10.005
Popis: The study of HIV-1 and HIV-2 protease inhibition of amprenavir is of immense therapeutic interest, owing to its application in the design of drugs, for the treatment of AIDS. Since, the inhibition is dependent on the molecular structural features, the DFT aided FT-IR, 13C NMR and FT-Raman spectral and structural analysis have been carried out, to arrive at the structure activity correlation. The negative mesomeric effect (–M effect) induced by the sulphonamide group and the consequent electron flow through APS (aminophenyl sulphonamide) ring has been explored using DFT and QTAIM based spectral analysis. The charge redistribution in the ring and the changes in bond strength arising due to this electron flow, have been investigated using experimental and theoretical methods. The relative strength of resonance of oxygen and nitrogen lone pair with the carbonyl group, due to ‘competing resonance’, have been exploited, using relative change in IR stretching frequencies and bond lengths of C-N and C-O. The role of π-anion interaction, favored by the electron deficiency of APS ring due to –M effect and the cooperativity of bonding has been examined using ESP mapping, quadrupole moment and the polarizability perpendicular to the ring. The stable binding pose of amprenavir in the binding site of HIV-1 and HIV-2 and amprenavir-residue interaction, obtained from docking, have been confirmed respectively using RMSD and simulation interaction diagram, procured from molecular dynamics simulation.
Databáze: OpenAIRE
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