Angiotensin-converting enzyme inhibitory activity of polyphenolic compounds from Peperomia pellucida (L) Kunth: An in silico molecular docking study

This study aimed to predict the potential activity and interaction conformation of polyphenolic compounds fromPeperomia pellucida (L) Kunth (nine compounds) with angiotensin-converting enzyme (ACE) macromolecule by insilico molecular docking study. The crystal structure of ACE as a molecular target was obtained from the PDB database(PDB ID: 1UZF) with captopril as a native ligand. Molecular docking analysis was performed using AutoDockZn (100docking runs) based on the active site of Zn2+, the central grid was placed on Zn2+ with a box size of 40Á × 40Á ×40Á and a center of 40.835Á × 34.382Á × 44.607Á for selective inhibitors (MCO702) with a spacing of 0.375Á.Based on the docking results demonstrated that the prediction of each polyphenol compounds from P. pellucida hasthe potential of active as ACE inhibitors, it was indicated that docking results of each compound has lower affinitycompared to captopril (with binding affinity of −6.36 kcal/mol and the inhibition constant 21.81 μM), where themost moderate binding affinity (the most potential) was tetrahydrofuran lignin ((1R,2S,3S,5R)-3,5-bis(4-hydroxy3,5-dimethoxyphenyl)cyclopentane-1,2-diyl)bis-(methylene) diacetate) of −8.66 kcal/mol and the highest bindingaffinity (the less potential) was dillapiole (6-allyl-4,5-dimethoxybenzo[d][1,3]dioxole) of −4.99 kcal/mol, althoughwith different forms of interaction, bond, and constant inhibition. Based on the interaction of ACE binding site,5,6,7-trimethoxy-4-(2,4,5-trimethoxyphenyl)-3,4-dihydronaphthalen-1(2H)-one showed the most similar interactionwith the captopril ligand. These results are preliminary data for further research with predictions of target compoundbiological activity and interaction quickly, accurately, and inexpensively

Targeting folate metabolism for therapeutic option: A bioinformatics approach.

Lymphatic filariasis, commonly called elephantiasis, poses a burden of estimated level of 5.09 million disability adjusted life year. Limitations of its sole drug, diethylcarbamazine (DEC) drive exploration of effective filarial target. A few plant extracts having polyphenolic ingredients and some synthetic compounds possess potential dihydrofolate reductase (DHFR) inhibitory effect. Here, we postulated a plausible link between folates and polyphenolics based on their common precursor in shikimate metabolism. Considering its implication in structural resemblance based antagonism, we have attempted to validate parasitic DHFR protein as a target. The bioinformatics approach, in the absence of crystal structure of the proposed target, used to authenticate and for virtual docking with suitable tested compounds, showed remarkably lower thermodynamic parameters as opposed to the positive control. A comparative docking analysis between human and Brugia malayi DHFR also showed effective binding parameters with lower inhibition constants of these ligands with parasitic target, but not with human counterpart highlighting safety and efficacy. This study suggests that DHFR could be a valid drug target for lymphatic filariasis, and further reveal that bioinformatics may be an effective tool in reverse pharmacological approach for drug design.