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Design, Synthesis, Pharmacological evaluation, in silico modeling, prediction of toxicity and metabolism studies of novel 1-(substituted)-2-methyl-3-(4-oxo-2-phenyl quinazolin-3(4H)-yl)isothioureas


M. T. Sulthana, V. Alagarsamy* and K. Chitra   Pages 1 - 17 ( 17 )


Background: Although exhaustive efforts to prevent and treat tuberculosis (TB) was taken the problem still continues due to multi-drug-resistant (MDR) and extensively drug resistant TB (XDR-TB). It clearly highlights the urgent need to develop novel “druggable” molecules for the co-infection treatment and strains of MDR-TB and XDR-TB.

Objective: In this approach a hybrid molecule was created by merging two or more pharmacophores. Active site of targets may be addressed by each of the pharmacophores and proffers the opportunity for selectivity. In addition, it also reduced the undesirable side effects and drug-resistant.

Methods: In this study, a novel quinazolinone analog was designed and synthesized by substituting thiourea nucleus and phenyl ring at N-3 and C-2 position of quinazoline ring respectively. All title compounds were tested for antitubercular activity by in-vitro M. tuberculosis and anti-human immunodeficiency virus (HIV) activity by MT-4 cell assay method. The agar dilution method was used to test the antibacterial potency of entire prepared derivatives against various strains of gram positive and gram-negative microorganism.

Results: The title compounds, 1-(substituted)-2-methyl-3-(4-oxo-2-phenyl quinazolin-3(4H)-yl) isothioureas (QTS1 – QTS15) are synthesized by reaction between key intermediate 3-amino-2-phenylquinazolin-4(3H)-one with various alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. Among the series, compound 1-(3-chlorophenyl)-2-methyl-3-(4-oxo-2-phenyl quinazolin- 3(4H)-yl) isothioureas (QTS14) shown highest potency against B. subtilis, K. pneumonia and S. aureus at 1.6 µg/mL. The compound QTS14 exhibited the most potent antitubercular activity at with the MIC of 0.78 µg/mL and anti-HIV activity at 0.97µg/mL against HIV1 and HIV2.

Conclusion: The results obtained from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities. The new scaffolds for proffers plausible lead for further development and optimization to novel antitubercular and anti-HIV drugs.


Quinazoline, graph theoretical analysis, substituted thiosemicarbazide, antibacterial activity, antitubercular activity, Anti-HIV activity.


Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy - 502 294, Gr.Hyderabad, Medicinal Chemistry Research Laboratory, MNR College of Pharmacy, Sangareddy - 502 294, Gr.Hyderabad, Faculty of Pharmacy, Sri Ramachandra Institute of Higher education and Research (Deemed to be University), Porur, Chennai, 600 116

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