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

• Published in: Pharmaceutical chemistry journal Vol. 55; no. 1; pp. 54 - 59
• Main Authors: Narendhar, B., Chitra, K., Alagarsamy, V.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.04.2021
• Subjects: Medicine; Organic Chemistry; Pharmacology/Toxicology; Pharmacy; substituted thiosemicarbazide; quinazolinone; antibacterial activity, antitubercular activity, anti-HIV activity; condensed pyrimidine
• ISSN: 0091-150X; 1573-9031
• DOI: 10.1007/s11094-021-02371-7

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(3 H) -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 EC 50 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.