Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen, 37077 Göttingen, Germany.
Bioorg Med Chem Lett. 2011 Aug 15;21(16):4728-31. doi: 10.1016/j.bmcl.2011.06.074. Epub 2011 Jun 23.
Control and prevention of tuberculosis is a major challenge, as one-third of the world's population is infected with Mycobacterium tuberculosis. The resurgence of tuberculosis and the emergence of multidrug-resistance strains of mycobacteria, necessitate the search for new class of antimycobacterial agents. As a part of investigation of new antitubercular agents in this laboratory, we describe the syntheses of various hydrazides of comarins, quinolones and pyrroles and screening against M. tuberculosis (Mtb) H37(Rv) by using rifampin as a standard drug. Among the designed molecules, the most prominent compounds 2a-g, 4a and 9a showed >90% GI at MIC<6.25 μg/mL. Finally, these studies suggests that compounds 2a-g, 4a and 9a may serve as promising lead scaffolds for further generation of new anti-TB agents.
控制和预防结核病是一个重大挑战，因为全球有三分之一的人口感染了结核分枝杆菌。结核病的死灰复燃以及耐多药分枝杆菌菌株的出现，需要寻找新的抗分枝杆菌药物。作为本实验室研究新抗结核药物的一部分，我们描述了各种考玛林、喹诺酮和吡咯的酰肼的合成，并使用利福平作为标准药物对结核分枝杆菌（Mtb）H37（Rv）进行了筛选。在所设计的分子中，最突出的化合物 2a-g、4a 和 9a 在 MIC<6.25μg/mL 时表现出 >90%的 GI。最后，这些研究表明，化合物 2a-g、4a 和 9a 可能作为有前途的先导骨架，进一步生成新的抗结核药物。
