Antitubercular antihiv and antibacterial activities of condensed pyrimidines and its analogues

Abstract

Coinfection of Tuberculosis and Human Immunodeficiency Virus possesses a tremendous challenge to TB control. Condensed pyrimidine derivatives attracted the medicinal chemists and pharmacologists because of its potential druggable behavior and 2 and 3 disubstituted condensed pyrimidines possesses potential for further developmentas antimicrobial agents By adopting hybrid approach in the present study using the condensed pyrimidine scaffold we have aimed to develop potent antitubercular antiHIV and antibacterial agents by merging two pharmacophores Four different novel series of substituted condensed pyrimidines have been synthesized and characterized by their spectral data IR NMR Mass spectra and elemental analysis and evaluated for their antitubercular antiHIV and antibacterial activities We have also performed the computational studies as mentioned below for the selected PTS series Graph theoretical analysis Density functional theory Molecular docking ADME and Toxicity studies SOM prediction by using SMARTCyp module Among the title compounds the compound 2 methyl 3 and 3 minus 3 to nitrophenyl minus 4 to oxo minus 3 and 4 minus dihydrobenzo pyrimidin to 2 to yl amino 1 to 3 to chlorophenyl isothiourea PTS 14 exhibited the most potent activity It showed antiTB antiHIV and antibacterial activity at MIC of 1 point 56and#956;g by ml 0 point 96 ug by mL and 1 point 6 ug by mL respectively and it also showed potent and selective interaction towards the target pan C protein with the good docking score of 8 point 039 Thus the compound PTS14 is found to be a lead molecule for further development and optimization to develop into a novel class of antitubercular and anti HIV drugs newline