Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City 11829, Egypt.
Department of Chemistry, University of Cambridge, Cambridge CB2 1EW, UK.
Molecules. 2022 Dec 12;27(24):8807. doi: 10.3390/molecules27248807.
We describe the design and synthesis of two isatin-tethered quinolines series (- and -), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound disclosed the highest potency with MIC value equal to 6.24 µg/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules -. Thereafter, the isatin motif was -substituted with either a methyl or benzyl group to furnish the second series -. All of the designed quinoilne-isatin conjugates - and - were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the -benzyl-bearing compound possessed the best activities against the examined strains with MICs equal 0.06, 0.24, and 1.95 µg/mL, respectively.
我们描述了两个靛红连接的喹啉系列（-和-）的设计和合成，这与我们开发新型含靛红的抗结核候选药物的研究兴趣有关。在之前的研究中，开发了一系列含有喹啉-3-甲酰肼部分的小分子作为抗结核剂，化合物 显示出最高的效力，MIC 值等于 6.24 µg/mL。在当前的工作中，我们采用生物等排体替换方法，用 TB 药物发现中的一个特权支架靛红基取代先导化合物 中的 3,4,5-三甲氧基苯亚甲基部分，提供了第一个目标分子系列-。此后，用甲基或苄基取代靛红基，得到第二个系列-。设计的所有喹啉-靛红缀合物 - 和 - 都进行了合成，并对其抗结核活性进行了评估，针对药敏、耐多药和广泛耐药菌株。优越的是，-苄基化合物 对所检查的 菌株具有最好的活性，MIC 值分别为 0.06、0.24 和 1.95 µg/mL。
