Synthesis of New 1-Substituted-3-(3-(2-Chlorophenyl)-4-Oxo-3,4-Dihydrobenzopyrimidin-2-Ylamino)Isothioureas as Anti-HIV and Antibacterial Agents

Abstract

In this study, a new benzopyrimidine analog was designed and synthesized by substituting 3-nitrophenyl ring and thiosemicarbazide nucleus at N-3 and C-2 positions of quinazoline ring, respectively. The title compounds, 1-substituted-3-(3-(2-chlorophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)isothioureas 7A – 7J were obtained via reactions of 2-hydrazino-3-(2-chlorophenyl)quinazolin-4(3H)-one (5) with different alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. All synthesized compounds were screened for their antitubercular, anti-HIV, and antibacterial activity against selected Gram-positive and Gram-negative bacteria using agar diffusion method. Amongst, compounds 2-methyl-3-(3-(2-chlorophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)-1-(3-chloropheny)isothiourea (7I) and 2-methyl-3-(3-(2-chlorophenyl)-4-oxo-3,4-dihydrobenzopyrimidin-2-ylamino)-1-(3-chlorophenyl)isothiourea (7F) showed the most potent activity against P. vulgaris and S. aureus with a MIC of 3 μg/mL. Compound 7I exhibited antitubercular activity at a minimum MIC of 3.125 μg/mL and anti-HIV activity at EC50 of 2.91 μg/mL against HIV1 and HIV2, thus offering probable lead for further development and optimization of new antitubercular and anti-HIV drugs. Results obtained in this study confirm that the synthesized and biologically evaluated benzopyrimidines possess promising antimicrobial, antitubercular, and anti-HIV properties and provide new scaffolds for antimicrobial activity.