STUDY OF ITRACONAZOLE

Abstract

This dissertation presents a comprehensive study of the Itraconazole, an FDA and CDSCO-approved medication primarily indicated for fungal infections. Itraconazole's efficacy stems from its binding affinity to plasma proteins within the human body, resulting in potent inhibition of cytochrome P450 and its associated enzymes, thereby augmenting its antifungal properties. The pharmacological mechanism of Itraconazole has been extensively investigated both in vitro and in vivo to elucidate its multifaceted actions. Beyond its established antifungal role, Itraconazole has garnered attention for its successful repurposing in treating viral infections, notably dengue, chikungunya, Ebola, and influenza. Emerging research has unveiled Itraconazole's potential in impeding cancer cell proliferation through modulation of various pathways including mTOR, VEGFR2, and Hh pathways. Notably, initiation of Itraconazole treatment curtailed up regulation of the Hh pathway, facilitating normal cellular processes of autophagy and apoptosis. This repurposing has shown promising outcomes in diverse cancers such as ovarian, breast, colorectal, liver, and basal cell carcinomas. Notably, in the context of the COVID-19 pandemic, Itraconazole has demonstrated potential in targeting the SARS-CoV-2 virus, specifically in its pre- and post-fusion conformations, exhibiting notable resistance against both MERS-CoV-2 and SARS-CoV-2 strains. The repurposing of Itraconazole represents a significant advancement in pharmacotherapy, extending its utility beyond fungal infections to encompass a spectrum of viral infections, cancer treatment, and potential mitigation against emerging infectious diseases such as COVID-19.