ANTIFUNGAL AGENTS: A COMPREHENSIVE REVIEW OF MECHANISMS AND APPLICATIONS
Main Article Content
Keywords
Antifungal agents, Mechanisms of action, Immunomodulation, Azoles, Antifungal Therapy
Abstract
Introduction: Antifungal resistance poses a significant challenge in the management of fungal infections. Understanding the mechanisms of action of antifungal agents is crucial for developing effective treatment strategies.
Objective: This comprehensive review delves into the intricate world of antifungal agents, offering insights into their diverse mechanisms, current applications, and potential future directions.
Mechanisms of Action: Polyene Antifungals: Disruption of fungal cell membrane integrity through binding to ergosterol. Azoles: Inhibition of ergosterol biosynthesis via binding to lanosterol 14α-demethylase. Echinocandins: Inhibition of β-(1,3)-D-glucan synthesis, leading to cell wall destabilization. Allylamines: Inhibition of squalene epoxidase, a key enzyme in ergosterol biosynthesis. Pyrimidine Analogues: Interference with nucleic acid synthesis by inhibiting dihydrofolate reductase. Efflux pumps: Extrusion of antifungal agents from fungal cells, reducing intracellular drug concentrations. Target alteration: Mutations in drug targets, such as lanosterol 14α-demethylase or β-(1,3)-D-glucan synthase, impairing drug binding. Ergosterol pathway alterations: Upregulation of alternative pathways bypassing drug targets. Biofilm formation: Enhanced resistance through biofilm-mediated protection. Systemic Treatment of invasive fungal infections, including candidiasis and aspergillosis. Topical Management of superficial fungal infections like dermatophytosis and candidiasis. Prevention of fungal infections in high-risk patients, such as those undergoing chemotherapy or organ transplantation. Control of fungal infections in animals, improving livestock health and production.
Challenges and Future Perspectives: Emergence of multidrug-resistant fungal strains. Development of novel antifungal agents with improved efficacy and safety profiles. Strategies to overcome resistance mechanisms, including combination therapy and drug repurposing. Importance of surveillance programs to monitor antifungal resistance trends globally.
Conclusion: Antifungal agents play a critical role in the management of fungal infections. Continued research efforts are necessary to address challenges associated with antifungal resistance and to develop innovative therapeutic approaches.
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4. Anzar, N., Hasan, R., Tyagi, M., Yadav, N., & Narang, J. (2020). Carbon nanotube - A review on Synthesis, Properties and plethora of applications in the field of biomedical science. Sensors International, 1, 100003.
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12. Bugeda, A., Garrigues, S., Gandía, M., Manzanares, P., Marcos, J. F., & Coca, M. (2020). The Antifungal Protein AfpB Induces Regulated Cell Death in Its Parental Fungus Penicillium digitatum. mSphere, 5(4).
13. Cafarchia, C., Figueredo, L. A., & Otranto, D. (2013). Fungal diseases of horses. Veterinary Microbiology, 167(1–2), 215–234.
14. Campitelli, M., Zeineddine, N., Samaha, G., & Maslak, S. (2017). Combination Antifungal Therapy: A Review of Current Data. Journal of Clinical Medicine Research, 9(6), 451–456.
15. Campoy, S., & Adrio, J. L. (2017). Antifungals. Biochemical Pharmacology, 133, 86–96.
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17. Chand, P., Kumari, S., Mondal, N., Singh, S. P., & Prasad, T. (2021). Synergism of Zinc Oxide Quantum Dots with Antifungal Drugs : Potential Approach for Combination Therapy against Drug Resistant Candida albicans, 3(May), 1–13.
18. Chanyachailert, P., Leeyaphan, C., & Bunyaratavej, S. (2023). Cutaneous Fungal Infections Caused by Dermatophytes and Non-Dermatophytes: An Updated Comprehensive Review of Epidemiology, Clinical Presentations, and Diagnostic Testing. Journal of Fungi, 9(6), p.669.
19. Chen, X., Ren, B., Chen, M., Liu, M.-X., Ren, W., Wang, Q.-X., et al. (2014). ASDCD: Antifungal Synergistic Drug Combination Database. PLoS ONE, 9(1), e86499.
20. Cortés, J. C. G., Curto, M.-Á., Carvalho, V. S. D., Pérez, P., & Ribas, J. C. (2019). The fungal cell wall as a target for the development of new antifungal therapies. Biotechnology Advances, 37(6), 107352.
21. Cotter, G., & Kavanagh, K. (2000). Adherence mechanisms of Candida albicans. British journal of biomedical science, 57(3), 241–9.
22. Cowen, L. E., Sanglard, D., Howard, S. J., Rogers, P. D., & Perlin, D. S. (2015). Mechanisms of Antifungal Drug Resistance. Cold Spring Harbor Perspectives in Medicine, 5(7), a019752.
23. Cruz, R., & Wuest, W. M. (2023). Beyond ergosterol: Strategies for combatting antifungal resistance in Aspergillus fumigatus and Candida auris. Tetrahedron, 133, 133268.
24. Deseta, M. L., Sponton, O. E., Finos, M. B., Cuffia, F., Torres-Nicolini, A., Álvarez, V. A., et al. (2023). Development of Antifungal Films from Nanocomplexes Based on Egg White Protein Nanogels and Phenolic Compounds. Food Biophysics, 18(2), pp.273-288.
25. DIN, A., MITREA, I., & MITREA, R. (2023). Natural compounds: an effective and eco-friendly strategies for controlling and combating plant pathogens. Notulae Botanicae Horti Agrobotanici Cluj-Napoca, 51(1), 12991.
26. Du Bois, A. C., Xue, A., Pham, C., Revie, N. M., Meyer, K. J., Yashiroda, Y., et al. (2022). High-Throughput Chemical Screen Identifies a 2,5-Disubstituted Pyridine as an Inhibitor of Candida albicans Erg11. mSphere, 7(3), pp.e00075-22.
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Oct 16, 2022
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Manju Singh, Neha, Gurpreet, Arvind Rathour, Uma Dey, Dr. Praveen Kumar Gaur, & Vijay Kumar. (2022). ANTIFUNGAL AGENTS: A COMPREHENSIVE REVIEW OF MECHANISMS AND APPLICATIONS. Journal of Population Therapeutics and Clinical Pharmacology, 29(04), 1343–1358. https://doi.org/10.53555/jptcp.v29i04.4351
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Author Biographies
Manju Singh
Dr. K.N. Modi Institute of Pharmaceutical Education and Research, Modinagar, Uttar Pradesh-201204
Neha
Dr. K.N. Modi Institute of Pharmaceutical Education and Research, Modinagar, Uttar Pradesh-201204
Gurpreet
Dr. K.N. Modi Institute of Pharmaceutical Education and Research, Modinagar, Uttar Pradesh-201204
Arvind Rathour
School of Pharmacy, Monad University, N.H. 9, Delhi Hapur Road, Dist. Hapur (U.P), Pilkhuwa-245304
Uma Dey
H.R. Institute of Pharmacy, Ghaziabad, 7th KM Stone Delhi Meerut Road Morta Ghaziabad, UP- 201003
Dr. Praveen Kumar Gaur
Metro College of Health Science and Research, Knowledge Park 3, Greater Noida, Uttar Pradesh-201308
Vijay Kumar
Deparment of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard New Delhi, India- 110062