Nahide Pradip D, Alba-Betancourt Clara, Chávez-Rivera Rubén, Romo-Rodríguez Pamela, Solís-Hernández Manuel, Segura-Quezada Luis A, Torres-Carbajal Karina R, Gámez-Montaño Rocío, Deveze-Álvarez Martha A, Ramírez-Morales Marco A, Alonso-Castro Angel J, Zapata-Morales Juan R, Ruiz-Padilla Alan J, Mendoza-Macías Claudia L, Meza-Carmen Victor, Cortés-García Carlos J, Corrales-Escobosa Alma R, Núñez-Anita Rosa E, Ortíz-Alvarado Rafael, Chacón-García Luis, Solorio-Alvarado César R
Universidad de Guanajuato, Campus Guanajuato, División de Ciencias Naturales y Exactas, Departamento de Química, Noria Alta S/N, 36050 Guanajuato, Gto., Mexico.
Universidad de Guanajuato, Campus Guanajuato, División de Ciencias Naturales y Exactas, Departamento de Farmacia, Noria Alta S/N, 36050 Guanajuato, Gto., Mexico.
Bioorg Med Chem Lett. 2022 May 1;63:128649. doi: 10.1016/j.bmcl.2022.128649. Epub 2022 Mar 1.
Zygomycetes are ubiquitous saprophytes in natural environments which transform organic matter. Some zygomycetes of gender Mucor have attracted interest in health sector. Due to its ability as opportunistic microorganisms infecting immuno-compromised people and to the few available pharmacological treatments, the mucormycosis is receiving worldwide attention. Concerning to the pharmacological treatments, some triazole-based compounds such as fluconazole are extensively used. Nevertheless, we focused in the quinolines since they are broadly used models for the design and development of new synthetic antifungal agents. In this study, the fungistatic activity on M. circinelloides of various 2-aryl-4-aryloxyquinoline-based compounds was discovered, and in some cases, it resulted better than reference compound fluconazole. These quinoline derivatives were synthesized via the C-O bond formation using diaryliodonium(III) salts chemistry. A QSAR study was carried out to quantitatively correlate the chemical structure of the tested compounds with their biological activity. Also, a docking study to identify a plausible action target of our more active quinolines was carried out. The results highlighted an increased activity with the fluorine- and nitro-containing derivatives. In light of the few mucormycosis pharmacological treatments, herein we present some non-described molecules with excellent in vitro activities and potential use in the mucormycosis treatment.
接合菌是自然环境中普遍存在的腐生菌，可转化有机物。一些毛霉属的接合菌引起了卫生部门的关注。由于其作为机会性微生物感染免疫功能低下人群的能力以及可用的药物治疗较少，毛霉病正受到全球关注。关于药物治疗，一些基于三唑的化合物如氟康唑被广泛使用。然而，我们关注喹啉类化合物，因为它们是新合成抗真菌剂设计和开发中广泛使用的模型。在本研究中，发现了各种基于2-芳基-4-芳氧基喹啉的化合物对卷枝毛霉的抑菌活性，在某些情况下，其效果优于参考化合物氟康唑。这些喹啉衍生物是通过使用二芳基碘鎓（III）盐化学方法形成C-O键合成的。进行了定量构效关系（QSAR）研究，以将测试化合物的化学结构与其生物活性进行定量关联。此外，还进行了对接研究，以确定我们活性更高的喹啉类化合物可能的作用靶点。结果突出显示含氟和含硝基的衍生物活性增加。鉴于毛霉病的药物治疗较少，在此我们展示了一些未描述的分子，它们具有出色的体外活性，在毛霉病治疗中具有潜在用途。
