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The alcoholic extract from seed kernels of Thai mango (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloylglucopyranose) exhibited potent, dose-dependent inhibitory effects on tyrosinase with respect to L-DOPA. Molecular docking studies revealed that the binding orientations of the phenolic principles were in the tyrosinase binding pocket and their orientations were located in the hydrophobic binding pocket surrounding the binuclear copper active site. The results indicated a possible mechanism for their anti-tyrosinase activity which may involve an ability to chelate the copper atoms which are required for the catalytic activity of tyrosinase.

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The ethanolic extract from seed kernels of Thai mango (MSKE) (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloyl glucopyranose) exhibited dose-dependent inhibitory effects on enzymatic activities of phospholipase A2 (PLA2), hyaluronidase and L-amino acid oxidase (LAAO) of Calloselasma rhodostoma (CR) and Naja naja kaouthia (NK) venoms by in vitro tests. The anti-hemorrhagic and anti-dermonecrotic activities of MSKE against both venoms were clearly supported by in vivo tests. Molecular docking studies indicated that the phenolic molecules of the MSKE could selectively bind to the active sites or their proximity, or modify conserved residues that are critical for the catalysis of PLA2, and selectively bind to the LAAO binding pocket of both CR and NK venoms and thereby inhibit their enzymatic activities. The results imply a potential use of MSKE against snake venoms.

Snakebite envenomations cause severe local tissue necrosis and the venom metalloproteinases are thought to be the key toxins involved. In this study, the ethanolic extract from seed kernels of Thai mango (Mangifera indica L. cv. ‘Fahlun’) (Anacardiaceae) and its major phenolic principle (pentagalloylglucopyranose) exhibited potent and dose−dependent inhibitory effects on the caseinolytic and fibrinogenolytic activities of Malayan pit viper and Thai cobra venoms in in vitro tests. Molecular docking studies revealed that the binding orientations of the phenolic principles were in the binding pockets of snake venom metalloproteinases (SVMPs). The phenolic principles could form hydrogen bonds with the three histidine residues in the conserved zinc−binding motif and could chelate the Zn2+ atom of the SVMPs, which could potentially result in inhibition of the venom enzymatic activities and thereby inhibit tissue necrosis.

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Human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT) is an important target for antiviral therapy against acquired immunodeficiency syndrome. However, the efficiency of available drugs is impaired most typically by drug-resistance mutations in this enzyme. In this study, we applied a nuclear magnetic resonance (NMR) spectroscopic technique to the characterization of the binding of HIV-1 RT to various non-nucleoside reverse transcriptase inhibitors (NNRTIs) with different activities, i.e., nevirapine, delavirdine, efavirenz, dapivirine, etravirine, and rilpivirine. 1H-13C heteronuclear single-quantum coherence (HSQC) spectral data of HIV-1 RT, in which the methionine methyl groups of the p66 subunit were selectively labeled with 13C, were collected in the presence and absence of these NNRTIs. We found that the methyl 13C chemical shifts of the M230 resonance of HIV-1 RT bound to these drugs exhibited a high correlation with their anti-HIV-1 RT activities. This methionine residue is located in proximity to the NNRTI-binding pocket but not directly involved in drug interactions and serves as a conformational probe, indicating that the open conformation of HIV-1 RT was more populated with NNRTIs with higher inhibitory activities. Thus, the NMR approach offers a useful tool to screen for novel NNRTIs in developing anti-HIV drugs.

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