State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing, 100050, PR China; Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing, 100050, PR China; Chinese Academy of Medical Sciences Key Laboratory of Anti-DR TB Innovative Drug Research, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, 1 Xian Nong Tan Street, Beijing, 100050, PR China.
Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, 97 Ma Chang Street, Beijing, 101149, PR China.
Eur J Med Chem. 2020 Mar 1;189:112075. doi: 10.1016/j.ejmech.2020.112075. Epub 2020 Jan 19.
A series of 4H-chromen-4-one derivatives obtained by scaffold morphing of the benzofuran compound, TAM16, were tested for antitubercular activity. Compound 8d was active against drug-sensitive and multidrug-resistant tuberculosis. A preliminary druggability evaluation showed that compound 8d displayed favorable mouse and human microsomal stability, low cytotoxicity, and acceptable oral bioavailability. An in vivo study indicated that compound 8d exhibited modest efficacy in an acute mouse model of TB after 3 weeks of treatment. Thus, 8d is a promising antituberculosis lead compound.
一系列通过苯并呋喃化合物 TAM16 的支架变形得到的 4H-色烯-4-酮衍生物被测试了抗结核活性。化合物 8d 对敏感和耐多药结核分枝杆菌均具有活性。初步的药物可开发性评估表明，化合物 8d 显示出良好的小鼠和人微粒体稳定性、低细胞毒性和可接受的口服生物利用度。体内研究表明，化合物 8d 在经过 3 周治疗后，在急性 TB 小鼠模型中表现出适度的疗效。因此，8d 是一种有前途的抗结核先导化合物。
