Anti-fungal effects of novel N-(tert-butyl)-2-(pyridin-2-yl)imidazo[1,2-a]pyridin-3-amine derivative and it's in-vitro, in-silico, and mode of action against Candida spp.

Autor: Nandhagopal M; Bio-Control and Microbial Product Lab, Department of Microbiology, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, 602105, India. micromani444@gmail.com., Mala R; Organic and Bioorganic Chemistry Laboratory, CSIR-Central Leather Research Institute, Adyar, Chennai, 600020, India., Somarathinam K; Centre for Advanced Studies in Crystallography and Biophysics, University of Madras, Guindy Campus, Chennai, 600 025, Tamil Nadu, India., Dhakshinamurthy D; Department of Chemistry, Vel Tech Rangarajan Dr, Sagunthala R&D Institute of Science and Technology, Avadi, Chennai, 600062, India., Narayanasamy M; Biocontrol and Microbial Metabolites Lab, Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India., Vijayan P; Biocontrol and Microbial Metabolites Lab, Centre for Advanced Studies in Botany, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India., Shankar MM; Department of Biochemistry, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, 602105, India.
Jazyk: angličtina
Zdroj: Archives of microbiology [Arch Microbiol] 2024 Mar 21; Vol. 206 (4), pp. 186. Date of Electronic Publication: 2024 Mar 21.
DOI: 10.1007/s00203-023-03780-w
Abstrakt: Imidazoles are a category of azole antifungals that encompass compounds such as ketoconazole, miconazole, esomeprazole, and clotrimazole. In contrast, the triazoles group, which includes fluconazole, voriconazole, and itraconazole, also plays a significant role. The rise of antibiotic resistance in fungal pathogens has evolved into a substantial global public health concern. In this study, two newly synthesized imidazo[1,2-a]pyridine derivative (Probe I and Probe II) molecules were investigated for its antimicrobial potency against of a panel of bacterial (Gram-positive and Gram-negative bacteria) and fungal pathogens. Among the different types of pathogens, we found that Probe II showed excellent antifungal activity against fungal pathogens, based on the preliminary screening the potent molecule further investigated against multidrug-resistance Candida sp. (n = 10) and compared with commercial molecules. In addition, in-silico molecular docking, its dynamics, absorption, distribution, metabolism, excretion and toxicity (ADMET) were analyzed. In this study, the small molecule (Probe II) displayed potent activity only against the Candida spp. including several multidrug-resistant Candida spp. Probe II exhibited minimum inhibitory concentration ranges from 4 to 16 µg/mL and minimum fungicidal concentration in the range 4‒32 µg/mL as the lowest concentration enough to eliminate the Candida spp. The selected molecules inhibit the formation of yeast to mold as well as ergosterol formation by the computational simulation against Sterol 14-alpha demethylase (CYP51) and inhibition of ergosterol biosynthesis by in-vitro model show that the Probe II completely inhibits the formation of ergosterol in yeast cells at 2× MIC. The ADMET analysis Probe II could be moderately toxic to the human being, though the in-vitro toxicity studies will help to understand the real-time toxic level. The novel compound Probe II, which was synthesized during the study, shows promise for development into a new generation of drug treatments aimed at addressing the emerging drug resistance in Candida sp.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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