molecules Communication Active Flavonoids from Colubrina greggii var. greggii S. Watson against Clinical Isolates of Candida spp. Elda M. Melchor-Martínez 1,2 , Juan F. Tamez-Fernández 1 , Gloria María González-González 3 , David A. Silva-Mares 1 , Noemí Waksman-Minsky 1 , Luis Alejandro Pérez-López 1 and Verónica M. Rivas-Galindo 1, *   Citation: Melchor-Martínez, E.M.; Tamez-Fernández, J.F.; González-González, G.M.; Silva-Mares, D.A.; Waksman-Minsky, N.; Pérez-López, L.A.; Rivas-Galindo, V.M. Active Flavonoids from Colubrina greggii var. greggii S. Watson against Clinical Isolates of Candida spp.. Molecules 2021, 26, 5760. https://doi.org/10.3390/molecules 26195760 Academic Editors: H. P. Vasantha Rupasinghe and Francesca Mancianti Received: 29 July 2021 Accepted: 15 September 2021 Published: 23 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Departamento de Química Analítica, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Av. Madero s/n, Colonia Mitras Centro, Monterrey 64460, Nuevo León, Mexico; elda.melchor@tec.mx (E.M.M.-M.); juan.tamezfrn@uanl.edu.mx (J.F.T.-F.); david.silvamr@uanl.edu.mx (D.A.S.-M.); noemi.waksmanmn@uanl.edu.mx (N.W.-M.); luis.perezlp@uanl.edu.mx (L.A.P.-L.) 2 School of Engineering and Sciences, Tecnologico de Monterrey, Monterrey 64849, Nuevo León, Mexico 3 Departamento de Microbiología, Facultad de Medicina, Universidad Autonoma de Nuevo Leon, Av. Madero s/n, Colonia Mitras Centro, Monterrey 64460, Nuevo León, Mexico; gloria.gonzalezgn@uanl.edu.mx * Correspondence: veronica.rivasgl@uanl.edu.mx; Tel.: +52-818-329-4185 Abstract: Candida albicans is the most commonly implicated agent in invasive human fungal infections. The disease could be presented as minimal symptomatic candidemia or can be fulminant sepsis. Candidemia is associated with a high rate of mortality and high healthcare and hospitalization costs. The surveillance programs have reported the distribution of other Candida species reflecting the trends and antifungal susceptibilities. Previous studies have demonstrated that C. glabrata more frequently presents fluconazole-resistant strains. Extracts from Mexican plants have been reported with activity against pulmonary mycosis, among them Colubrina greggii. In the present study, extracts from the aerial parts (leaves, flowers, and fruits) of this plant were evaluated against clinical isolates of several species of Candida (C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis) by the broth microdilution assay. Through bioassay-guided fractionation, three antifungal glycosylated flavonoids were isolated and characterized. The isolated compounds showed antifungal activity only against C. glabrata resistant to fluconazole, and were non-toxic toward brine shrimp lethality bioassay and in vitro Vero cell line assay. The ethyl acetate and butanol extracts, as well as the fractions containing the mixture of flavonoids, were more active against Candida spp. Keywords: antifungal activity; candida spp.; colubrina greggii var. greggii; bioassay-guided fractionation 1. Introduction Over the past two decades there has been a dramatic increase in the incidence of systemic fungal infections related to immuno-compromised patients, cancer chemotherapy, or organ transplant recipients [1]. Although medical advances made it possible to lengthen the life of these patients, they are highly susceptible to fungal infections, the majority of them are contributing to an increase in the mortality and morbidity in healthy and immunocompromised patients [2]. In addition, antifungal drugs often exert multiple adverse effects and are occasionally dose-limiting. Although there seems to be a good number of antifungal drugs in clinical use, there are few options for therapeutic use [3]. Besides the toxicity produced for some drugs (polyenes, allylamines, azoles, and recently developed echinocandin class of molecules) [4], others are fungistatic and non-fungicides producing recurrence and other ones development cross-resistance (5-Flucytosine) [5]. The above mentioned represent a real problem due to prolonged treatments. New drugs like posaconazole, ravuconazole, micafungin, and anidulafungin are being researched and are promising [6]. Molecules 2021, 26, 5760. https://doi.org/10.3390/molecules26195760 https://www.mdpi.com/journal/molecules