Antitubercular anti HIV and antibacterial activities of novel substituted quinazolines and its analogues

Abstract

The control of TB coinfection of TB with HIV makes a terrific challenge In recent years quinazoline derivatives gained much interest to medicinal chemists and pharmacologists because of its potential drug gable behaviour Amongst that antimicrobial activity of 2 and newline3 disubstituted quinazolines are encouraging for further development In this study using the quinazoline scaffold we have aimed to develop potent antitubercular antiHIV and antibacterial moieties based on pharmacophore hybrid approach by merging two pharmacophores Five different novel series of substituted quinazolines have been synthesized and characterized by their spectral data IR NMR Mass spectra and elemental analysis All the title compounds were tested for antitubercular antiHIV and antibacterial activities Following computational studies were also performed for the selected QTS series Graph theoretical analysis Density functional theory Molecular docking ADME and Toxicity studies using Qikpro module of Schrodinger 2016 SOM prediction by using SMARTCyp module Among the synthesized compounds the compound 1 to 3 chlorophenyl 2 methyl 3 and 4 oxo 2 phenylquinazolin 3 and 4H to yl isothiourea QTS to 14 exhibited the most potent activity It showed antiTB activity at the MIC of 0 point 79 and#956;g ml and antiHIV activity at the concentration of at 0 point 97 ug ml It also showed significant antibacterial activity at the MIC of 1 point 6 ug ml and it also showed potent and selective interaction towards the target pan C protein with the good docking score of 7 point 542 Thus the compound QTS14 emerged as a lead for further development and optimization to develop into a novel class of antitubercular and anti HIV drugs newline newline