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About me

Ph.D.-trained researcher and professional academic writer with over five years of combined research and writing experience, specializing in creating high-quality, evidence-based academic content across sciences, social sciences, management, arts, and social work. Have successfully provided writing and editorial support to more than 50 students and research scholars, from undergraduate to doctoral levels.

Interests: Leishmaniasis, a protozoan parasitic infection causing a significant global burden, demands innovative therapeutic strategies due to the limitations of current treatment therapeutics (toxicity, lengthy courses, resistance, and high cost). This present thesis work involves the exploration of novel chemical scaffolds targeting Sterol C-24 methyl transferase (SMT) and Sterol 14-α-demethylase (SDM) from the sterol biosynthesis pathway of the Leishmania parasite. The study involves a multi-faceted approach, integrating natural product screening, semi-synthetic modification, chemical synthesis, in silico-guided high-throughput screening (HTS), and drug repurposing. We identified promising anti-leishmanial candidates from diverse sources demonstrating potent in vitro activity against Leishmania donovani, with favorable selectivity indices and reduced intracellular amastigote burdens. Mechanistic investigations further revealed that these potent hits disrupt the parasite’s physiology through multiple pathways, including oxidative stress induction, ATP depletion, mitochondrial dysfunction, lipid accumulation, cell-cycle disruption, etc. Further, in silico studies, using molecular docking and dynamics simulations, highlighted the interaction of these hits with the target enzymes SMT and SDM of sterol biosynthetic pathway which was further validated by ergosterol depletion assay. Overall, this work presents compounds like 6 Methoxydihydrochelerythrine, anhydroparthenin, the eugenol-isoxazoline hybrid (8b), and pyrazole derivative (4j), along with repurposed drugs like Indocyanine green and Iohexol, as promising anti-leishmanial leads. Also, the in-house ChemBridge library yielded leishmanicidal molecules IIIM-CB-15 and IIIM-CB-45, while the ChemDiv library illustrated IIIM-CD-07, IIIM-CD-08, IIIM-CD-09 and IIIM-CD-10 as potent anti-leishmanial candidates. Altogether, the research provides a strong foundation for future drug discovery efforts aimed at combating this debilitating disease.