Synthesis, characterization: Spectral and theoretical, molecular docking and in vitro studies of copper complexes with HIV RT enzyme

Abstract

Millions of people are living with human immunodeficiency virus type 1 (HIV-1), which causes AIDS or AIDS- related complex. HIV-1 reverse transcriptase (RT) is one of the key viral targets for HIV-1 inhibition. In the present work, new Cu(II) heterocyclic Schiff base complexes as HIV-1 reverse transcriptase inhibitors have been synthesized. Complexes were characterized by NMR, FTIR, Mass, UV-Vis, EPR spectra, TGA, magnetic moment and elemental analyses. DFT based molecular orbital energy calculations of the synthesized copper complexes have been studied, in which the complexes were theoretically optimized. Geometrical structures of the complexes were found to be square pyramidal and square planar. To test the reverse transcriptase inhibition activity of the ligands and their Cu(Il) complexes, HIV-1 RT kit assay was used. Nevirapine was used as reference drug. Results showed that the newly synthesized copper complexes effectively inhibited HIV-1 replication. Thiophene copper complexes were found to exhibit higher anti-HIV activity than pyrrole copper complexes. Molecular docking was also used to identify the interaction between Cu(II) complexes with the active site of the RT enzyme (with PDB ID: 1S1U). The cytotoxicity of these copper complexes has been evaluated by MTT assay against normal 3T3L1 cells and results show that the synthesized copper complexes [Cu(T2)2], [Cu(P2)2] and [Cu(P3)2] are non toxic in nature.