Integrated Phytochemical Profiling and Computational Evaluation of Psidium Guajava L. Leaves as A Potential Source of Antimalarial Therapeutics

Abstract

The escalating prevalence of malaria, coupled with the rapid emergence of multidrug-resistant Plasmodium strains, necessitates the urgent discovery of novel, sustainable, and affordable antimalarial agents. Psidium guajava L. (guava) has long been utilized in traditional medicine across tropical regions for managing febrile illnesses; however, a comprehensive scientific validation of its phytochemical synergy and molecular mechanisms remains imperative. This study investigates the phytochemical landscape of Psidium guajava leaves using High Performance Liquid Chromatography (HPLC) and evaluates its therapeutic potential through an integrated computational framework. HPLC analysis revealed a diverse profile of 15 bioactive compounds, with Quercetin (53.08%, 0.5308 mol/L) identified as the predominant constituent, followed by Persin (14.98%) and Zeaxanthine (9.37%). Molecular docking simulations against key Plasmodium falciparum targets, including Dihydrofolate Reductase (PfDHFR) and Lactate Dehydrogenase (PfLDH), demonstrated high binding affinities for Quercetin and its derivatives, suggesting potent inhibitory potential. Furthermore, Density Functional Theory (DFT) calculations at the B3LYP/6-31G(d,p) level elucidated the electronic properties and radical scavenging mechanisms of the primary constituents, highlighting their role in mitigating malaria-induced oxidative stress. These findings provide a rigorous biochemical and computational foundation for the traditional use of P. guajava and position its phytochemicals as promising scaffolds for the development of next-generation antimalarial drugs.