Cruz-Martínez Yesica R, Hernández-Delgado Tzasna, Méndez-Cuesta Carlos A, Delgado Guillermo
Instituto de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, Coyoacán 04510, México.
Unidad de Biotecnología y Prototipos, Facultad de Estudios Superiores Iztacala, UNAM, Av. de los Barrios No. 1, Tlalnepantla 54090, Estado de México, México.
J Appl Microbiol. 2025 Jul 1;136(7). doi: 10.1093/jambio/lxaf160.
To evaluate the antifungal activity of sesquiterpenes from Heterotheca inuloides, estimate their sensitizing activity against resistant Candida glabrata and C. tropicalis, and elucidate the possible mechanisms of bioactivity through molecular docking.
The MIC of sesquiterpenes, fluconazole (FLU), voriconazole (VOR), clotrimazole (CLO), or their combination was determined by broth microdilution method. Compounds 5 and 7 showed the best antifungal activity with MIC of 37.5 and 75.0 μg/mL in C. tropicalis and C. glabrata, respectively. On the other hand, the sesquiterpenes increased the effectiveness of FLU, VOR, and CLO. The most significant sensitization effects to FLU were observed when combined with compounds 4 and 5, which reduced the MIC by 8-fold (from 256 to 32 μg/mL) in C. tropicalis and 4-fold (from 256 to 64 μg/mL) in C. glabrata. For VOR, compounds 5 and 6 decreased the MIC up to 4-fold (from 8 to 2 μg/mL) in both fungal strains. Compound 6 also reduced the MIC of CLO by up to 8-fold (from 64 to 8 μg/mL) in C. tropicalis. Finally, all sesquiterpenes were found to interact with the lanosterol 14α-demethylase and CDR efflux pump.
Sesquiterpenes exhibited moderate antifungal activity against resistant C. glabrata and C. tropicalis. They enhanced the effectiveness of FLU, VOR, and CLO. According to molecular docking, the antifungal and resistance-sensitizing activity could be attributed to the inhibition of lanosterol 14α-demethylase and CDR efflux pump, respectively.
评估来自糙叶泽兰的倍半萜的抗真菌活性，估计它们对耐药光滑念珠菌和热带念珠菌的致敏活性，并通过分子对接阐明生物活性的可能机制。
采用肉汤微量稀释法测定倍半萜、氟康唑（FLU）、伏立康唑（VOR）、克霉唑（CLO）或它们的组合的最低抑菌浓度（MIC）。化合物5和7表现出最佳抗真菌活性，在热带念珠菌和光滑念珠菌中，MIC分别为37.5和75.0μg/mL。另一方面，倍半萜提高了氟康唑、伏立康唑和克霉唑的有效性。与化合物4和5联合使用时，对氟康唑观察到最显著的致敏作用，在热带念珠菌中使MIC降低了8倍（从256降至32μg/mL），在光滑念珠菌中降低了4倍（从256降至64μg/mL）。对于伏立康唑，化合物5和6在两种真菌菌株中均使MIC降低高达4倍（从8降至2μg/mL）。化合物6在热带念珠菌中也使克霉唑的MIC降低高达8倍（从64降至8μg/mL）。最后，发现所有倍半萜均与羊毛甾醇14α-去甲基酶和CDR外排泵相互作用。
倍半萜对耐药光滑念珠菌和热带念珠菌表现出中等抗真菌活性。它们增强了氟康唑、伏立康唑和克霉唑的有效性。根据分子对接，抗真菌和耐药致敏活性分别可归因于对羊毛甾醇14α-去甲基酶和CDR外排泵的抑制。
