Novel 2-aryl-4-aryloxyquinoline-based fungistatics for Mucor circinelloides. Biological evaluation of activity, QSAR and docking study

• DOI: 10.1016/j.bmcl.2022.128649
• Publication Date: 2022-03-01T16:45:42Z
• Authors: Pradip D. Nahide; Clara Alba-Betanc...; Rubén Chávez-Rivera; Pamela Romo-Rodrí...; Manuel Solís-Hern...; Luis A. Segura-Qu...; Karina R. Torres-...; Rocío Gámez-Montaño; Martha A. Deveze-...; Marco A. Ramírez-...; Angel J. Alonso-C...; Juan R. Zapata-Mo...; Alan J. Ruiz-Padilla; Claudia L. Mendoz...; Victor Meza-Carmen; Carlos J. Cortés-...; Alma R. Corrales-...; Rosa E. Núñez-Anita; Rafael Ortíz-Alva...; Luis Chacón-García; César R. Solorio-...
• Keywords: 0301 basic medicine; 03 medical and health sciences; Mucor; Quinolines; Humans; Mucormycosis; Quantitative Structure-Activity Relationship; Fluconazole; 3. Good health

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 Csp2-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.