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In Vitro and In Silico Analysis of Ascorbic Acid Towards Lanosterol 14-α-Demethylase Enzyme of Fluconazole-Resistant Candida albicans

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Abstract

Antibiotic resistance is one of the major concerns and the biggest threats to the world population. The incidents of antibiotic resistance in Candida spp. were frequently recorded. In the present investigation, antifungal potential of ascorbic acid (AA) was evaluated. According to the in vitro analysis, the zone of inhibition of AA (24.75 ± 0.35 mm) against C. albicans was greater as compared to other vitamins tested. AA significantly modulate the growth of C. albicans at 25 mg/ml. The highest percentage (94.67%) of cell viability was observed in untreated cells, and low cell viability (29.36%) was observed in cells treated with 50 mg/ml of AA (2 × MIC). Further, AO/EB (acridine orange/ethidium bromide), propidium iodide staining, and real-time qPCR confirmed the loss of membrane integrity due to membrane lesions that caused cell death. Lanosterol 14-α-demethylase (L-14α-DM) is the product of ERG11 and acted as superior drug target of C. albicans. Molecular docking analysis confirmed that active interaction of ascorbic acid with L-14α-DM. Based on the present investigation, the efficiency of AA was effectively proved through the in vitro and in silico analysis. This finding has evidenced the effectiveness of AA as a potential candidate against C. albicans.

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Acknowledgements

All the authors are thankful to Professor S. Parthasarathy for the guidance and critical comments on the study. Molecular dynamics studies were performed using High Performance Computing (HPC) Facility [DST-PURSE (Grant No. SR/FT/LS-113/2009)] at University Informatics Centre, Bharathidasan University, Tiruchirappalli. They would like to thank Dr. Aananth, Sivan Bioscience for his valuable comments on language of the manuscript. They show their gratitude to Editor and reviewers of this manuscript for their valuable suggestion toward the improvement of this manuscript.

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Ganeshkumar, A., Suvaithenamudhan, S. & Rajaram, R. In Vitro and In Silico Analysis of Ascorbic Acid Towards Lanosterol 14-α-Demethylase Enzyme of Fluconazole-Resistant Candida albicans. Curr Microbiol 78, 292–302 (2021). https://doi.org/10.1007/s00284-020-02269-9

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