Background: Although exhaustive efforts to prevent and treat tuberculosis (TB) have
been made, the problem still continues due to multi-drug-resistant (MDR) and extensively drugresistant
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.
The active site of targets may be addressed by each of the pharmacophores and proffers the opportunity
for selectivity. In addition, it also reduces undesirable side effects and drug-resistance.
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 grampositive
and gram-negative microorganisms.
Results: The title compounds, 1-(substituted)-2-methyl-3-(4-oxo-2-phenyl quinazolin-3(4H)-yl)
isothioureas (QTS1 – QTS15) were synthesized by the 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) showed the 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 the MIC of 0.78 μg/mL and anti-HIV activity at 0.97 μg/mL against HIV1 and
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 proffer a plausible lead for further development and optimization of novel antitubercular
and anti-HIV drugs.