Elucidation of Antiplasmodial Activity of Phytocompounds in Nauclea latifolia: In silico Approach

Abstract

Nauclea latifolia is commonly used for treating malaria in Nigeria. Several studies on N. latifolia have shown its antimalarial activities; however, the mechanisms of the plant action against the malaria parasite remain unknown. Hence, this study elucidated the potential targets and pathways involved in the antimalarial activity of the phytocompounds in DCM-methanol (1:1) stem bark extract of N. latifolia. The phytocompounds were identified using the Gas chromatography-mass spectrometry technique. The Target proteins were obtained from Online Mendelian Inheritance in Man (OMIM), Ch-European Molecular Biology Laboratory, National Center for Biotechnology Information, and Gene Cards databases. Using the network pharmacology approach, the proteinprotein interaction and compound-target-pathway network were constructed with the STRING algorithm and Cytoscape, respectively. Thereafter, phytocompounds were subjected to molecular docking, and molecular dynamics simulation. Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) screening of the phytocompounds were performed using Admetlab 2.0, Protox II, and Admetsar 2.0. The Network Pharmacology results showed that most phytocompounds interact with key therapeutic genes involved in inflammatory responses and proteolysis pathways. Notable among the pathways are PI3K-Akt signalling, IL-17 signalling and HIF-1 signalling pathways. The key identified therapeutic targets of P. falciparum which the phytocompounds interacted with are MAPK1, HMOX1, MMP9, GSK3β, and IDO1. Molecular docking revealed that MMP9 and Furazano[3,4- b]cyclopentano[e][1,4]-diazepin-5(4H)-one,6,7,8,9-tetrahydro is the most favourable complex for drug development. The molecular dynamics simulation further validates the complex as the most stable. The ADMET analysis also shows that the compound has drug-likeness properties. This finding predicted the targets and pathways involved in the antimalarial effects of Nauclea latifola, and revealed Furazano[3,4-b]cyclopentano[e][1,4]-diazepin- 5(4H)-one,6,7,8,9-tetrahydro as a potential antimalarial drug candidate.