Review on Coumarins from the Genus Calophyllum: Molecular Interactions Against HIV Targets and Insights from Computational and Experimental Studies

The Calophyllum genus is a diverse group of tropical trees known for producing a wide variety of bioactive compounds, including xanthones, coumarins, triterpenoids, and flavonoids. Coumarins possess several pharmacological activities such as anti-HIV, anti-inflammatory, anti-bacterial, and anti-coagulation effects. Calanolide A, Calanolide B, and several Inophyllum derivatives are among the compounds that exhibit a significant inhibition of HIV-1 reverse transcriptase (RT) that is beyond the action of some HIV-1 RT inhibitors in market drugs. This research conducted the docking of HIV-1 RT and integrase (IN) to assess its antiviral coumarins derived from Calophyllum species. Coumarins are benzopyrones characterized by a conjugated aromatic system that is crucial for anchoring at the RT- NNRTI binding pocket and the IN catalytic core. Hydroxyl, methoxy, and acetoxy groups increase their binding affinity for enzymes and specificity. The molecular docking scores support these findings, where Inophyllum E, Soulattrolone, and other compounds show significantly better binding with RT and IN than the controls Efavirenz and Raltegravir. The impressive effectiveness can be attributed to their structural variety, hydrophobic interactions, and optimally placed functional groups, which allow for considerable and stable complexing within the active sites. Consequently, the Calophyllum coumarins are deemed valuable for the future development of novel antiviral drugs. HIGHLIGHTS Calophyllum species are rich sources of bioactive coumarins with notable pharmacological potential, particularly antiviral properties against HIV targets. Molecular docking demonstrated strong interactions of Calophyllum-derived coumarins with HIV-1 reverse transcriptase and integrase active sites. Key compounds such as Inophyllum E and Soulattrolide exhibited higher binding affinity than standard drugs Efavirenz and Raltegravir. Structural features including hydroxyl, methoxy, and acetoxy substituents enhance enzyme binding and stability within catalytic pockets. Calophyllum coumarins represent promising lead molecules for the development of next-generation anti-HIV therapeutics. GRAPHICAL ABSTRACT

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