Isolation and Characterisation of Akuammine from the Seed of <i>Parinari curatellifolia</i> and its Molecular Dynamics in Angiotensin -1- Converting Enzyme Inhibition

Olamide O. Crown; Samson O. Famuyiwa; Olanrewaju S. Olayeriju; Mary T. Olaleye; Victor I. Ogungbe; Derek T. Ndinteh

doi:10.26538/tjnpr/v8i5.37

Authors

Olamide O. Crown Department of Chemistry, College of Sciences, University of Alabama, Huntsville Alabama, 35899, USA.
Samson O. Famuyiwa Department of Chemistry, Faculty of Science, Obafemi Awolowo University, Nigeria.
Olanrewaju S. Olayeriju Department of Biochemistry, Olusegun Agagu University of Science and Technology, Okitipupa, Ondo state, Nigeria.
Mary T. Olaleye Department of Biochemistry, Phytomedicine, Toxicology and Pharmacology Unit, School of Sciences, Federal University of Technology, Akure, Nigeria.
Victor I. Ogungbe Department of Chemistry, College of Sciences, University of Alabama, Huntsville Alabama, 35899, USA.
Derek T. Ndinteh Department of Chemical Sciences, Faculty of Sciences, University of Johannesburg, Doonfortein campus, South Africa

DOI:

https://doi.org/10.26538/tjnpr/v8i5.37

Keywords:

Akuammine, Angiotensin converting enzyme, Antihypertension, Parinari curatellifolia

Abstract

Over the years, isolated compounds from medicinal plants have been lead candidates in drug discovery and they are useful therapeutic aid to patients. This work isolated a compound from the seed of Parinari curatellifolia and investigated its inhibitory potential and mechanism on angiotensin-1-converting enzyme (ACE1). The methanolic extract of the seed was subjected to chromatographic techniques and yielded a white, crystalline solid. Structural elucidation of the compound was carried out using NMR and MS spectroscopic techniques. The use of N-(3-[2-furyl-acryloyl]-Phe-Gly-Gly) (FAPGG) as an enzyme substrate and the Michealis-Menten method in this study showed how sensitive and fast ACE1 could be inhibited. Inhibition mechanism was explored using the Lineweaver-Burk model, and IC₅₀ was determined using Cheng-Prusoff empirical analysis. Molecular interaction with ACE1 was investigated computationally. NMR and MS spectroscopy showed the compound to be Akuammine, with 26 protons, 22 carbons, 2 nitrogen, and 4 oxygen atoms and chlorinated molecular ion peak at m/z 417.1593. Akuammine exhibited an IC₅₀ of 8.5 µM and displayed mixed type inhibition. Molecular dynamics simulations indicated strong interaction at the allosteric site of ACE1, primarily through hydrophobic interactions. Akuammine demonstrated an ability as a template for antihypertensive agent. This ability may contribute to the ethno botanical uses of Parinari curatellifolia seed.

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