Pertino Mariano Walter, F de la Torre Alexander, Schmeda-Hirschmann Guillermo, Vega Gómez Celeste, Rolón Miriam, Coronel Cathia, Rojas de Arias Antonieta, Molina-Torres Carmen A, Vera-Cabrera Lucio, Viveros-Valdez Ezequiel
Instituto de Química de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca 3480094, Chile.
Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53705, USA.
Pharmaceuticals (Basel). 2024 Oct 16;17(10):1375. doi: 10.3390/ph17101375.
In this study, the efficacy of benzo[h]chromene derivatives as antiprotozoal and antimycobacterial agents was explored. A total of twenty compounds, including benzo[h]chromene alkyl diesters and benzo[h]chromene-triazole derivatives, were synthesized and tested against , , , and strains of and LIID-01. Notably, compounds , , , and exhibited superior activity against , with IC values of 19.2, 37.3, 68.7, and 24.7 µM, respectively, outperforming the reference drug benznidazole (IC: 54.7 µM). Compounds and showed excellent selectivity indices against , with SI values of 19 and 18, respectively, suggesting they could be potential alternatives to the commonly used, but more selective, miltefosine (IC: 64.0 µM, SI: 43.0). Additionally, compounds , , and were most effective against , with IC values of 24.9, 30.5, and 46.6 µM, respectively. Compounds and were particularly potent against various strains, highlighting their significance given the inherent resistance of these bacteria to standard antimicrobials. The sensitivity of LIID-01 to these compounds also underscored their potential in managing infections by the Mycobacterium avium-intracellulare complex.
在本研究中，探索了苯并[h]色烯衍生物作为抗原生动物和抗分枝杆菌剂的功效。总共合成了20种化合物，包括苯并[h]色烯烷基二酯和苯并[h]色烯 - 三唑衍生物，并针对克氏锥虫、杜氏利什曼原虫、鸟分枝杆菌和胞内分枝杆菌菌株以及LIID - 01进行了测试。值得注意的是，化合物3、4、5和6对克氏锥虫表现出优异的活性，IC值分别为19.2、37.3、68.7和24.7 μM，优于参考药物苄硝唑（IC：54.7 μM）。化合物7和8对杜氏利什曼原虫显示出优异的选择性指数，SI值分别为19和18，表明它们可能是常用但选择性更高的米替福新（IC：64.0 μM，SI：43.0）的潜在替代品。此外，化合物9、10和11对鸟分枝杆菌最有效，IC值分别为24.9、30.5和46.6 μM。化合物12和13对各种胞内分枝杆菌菌株特别有效，鉴于这些细菌对标准抗菌药物具有固有抗性，突出了它们的重要性。LIID - 01对这些化合物的敏感性也强调了它们在管理鸟分枝杆菌 - 胞内分枝杆菌复合群感染方面的潜力。
