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 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 proffer a plausible lead for further development and optimization of novel antitubercular and anti-HIV drugs.

背景：尽管已经尽了全力预防和治疗结核病（TB），但由于多药耐药性（MDR）和广泛耐药性结核病（XDR-TB），该问题仍然存在。它清楚地突出显示了迫切需要开发新型的“可吸收”分子用于共感染治疗以及MDR-TB和XDR-TB菌株。

目的：通过这种方法，通过合并两个或多个药效基团来创建杂交分子。靶标的活性位点可以通过每个药效团来解决，并提供选择性的机会。此外，它还减少了不良的副作用和耐药性。

方法：在本研究中，设计了一种新颖的喹唑啉酮类似物，方法是分别在喹唑啉环的N-3和C-2位置取代硫脲核和苯环。通过体外结核分枝杆菌测试所有标题化合物的抗结核活性，并通过MT-4细胞测定法测试抗人类免疫缺陷病毒（HIV）的活性。琼脂稀释法用于测试整个制备的衍生物对各种革兰氏阳性和革兰氏阴性微生物的抗菌能力。

结果：通过关键中间体3之间的反应合成了标题化合物1-（取代）-2-甲基-3-（4-氧代-2-苯基喹唑啉-3（4H）-基）异硫脲（QTS1-QTS15） -氨基-2-苯基喹唑啉-4（3H）-1与各种烷基/芳基异硫氰酸酯，然后用硫酸二甲酯甲基化。在该系列中，化合物1-（3-氯苯基）-2-甲基-3-（4-氧代-2-苯基喹唑啉-3（4H）-基）异硫脲（QTS14）对枯草芽孢杆菌K的效价最高。肺炎和金黄色葡萄球菌的浓度为1.6μg/ mL。化合物QTS14在MIC上对HIV1和HIV2的抗结核活性最强，为0.78μg/ mL，而对HIV的抗HIV活性为0.97μg/ mL。

结论：从这项研究中获得的结果证实，合成并经过生物学评估的喹唑啉具有良好的抗菌，抗结核和抗HIV活性。新的支架为进一步开发和优化新型抗结核和抗HIV药物提供了合理的线索。