Page 64 - ITPS-7-1

INNOSC Theranostics

and Pharmacological Sciences

ORIGINAL RESEARCH ARTICLE
Plasmodium falciparum histoaspartic protease

inhibitor: Toxicity investigation and docking
study of 2-(2-benzoyl-4-methylphenoxy)

quinoline-3-carbaldehyde derivatives

Oluwafemi S. Aina , Luqman A. Adams , Adebayo J. Bello , and
1
2
1
Oluwole B. Familoni *
1
1 Drug Design Research Group, Department of Chemistry, University of Lagos, Lagos State, Nigeria
2 Department of Chemistry and Biology, Redemeer’s University, Osun State, Nigeria

Abstract
Aspartic proteases can hydrolyze peptide bonds, making them potential targets for
drug development against malaria parasites. In particular, inhibiting the histoaspartic
protease (HAP) can disrupt the growth phase of Plasmodium falciparum and its ability
to degrade hemoglobin for protein synthesis. Compound 5, specifically designed as
2-(2-benzoyl-4-methylphenoxy)quinoline-3-carbaldehyde, served as the basis for
designing 50 hypothetical compounds (A1-A50). These compounds were subjected to
in silico screening to assess their toxicity profiles, pharmacokinetics, bioactivity scores,
*Corresponding author:
Oluwole B. Familoni and theoretical binding affinities, as a part of the drug design protocol. Out of the 50
(familonio@unilag.edu.ng) compounds, nine lead candidates showed no toxicity to human cells. In addition, ten
standard reference antimalarial drugs were included in this study for comparison. The
Citation: Aina OS, Adams LA,
Bello AJ, et al., 2024, Plasmodium highest binding energies were observed for compound A5 (−11.2 kcal/mol) and A31
falciparum histoaspartic protease (−11.3 kcal/mol), surpassing the performance of mefloquine, the best reference drug,
inhibitor: Toxicity investigation and which ranked ninth with a binding energy of (−9.6 kcal/mol). Compound A31 did not
docking study of 2-(2-benzoyl-
4-methylphenoxy) quinoline-3- exhibit the evidence of interaction with either Asp215 or His32, whereas compound
carbaldehyde derivatives. INNOSC A5 displayed π-π stacking interactions with His . Mefloquine also did not show any
32
Theranostics and Pharmacological interaction with Asp215 or His32. Moreover, compound A5 demonstrated greater
Sciences, 7(1): 0976.
https://doi.org/10.36922/itps.0976 hydrophobic interactions at the active site with most binding residues, except for Lys
7
in the hydrophobic region. This characteristic suggests that compound A5 may have
Received: May 23, 2023
the ability to adopt a smaller surface area, exhibit increased biological activity, and
Accepted: July 26, 2023 have reduced interactions with water, which could facilitate slower clearance. Based
Published Online: September 13, on the assessment of various drug-likeness parameters, compound A5 (2-(2-benzoyl-
2023 4-methylphenoxy)-7-methylquinoline-3-carbaldehyde) is a potential lead candidate
Copyright: © 2023 Author(s). for the development of a new antimalarial drug.
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution Keywords: Malaria; Mefloquine; Binding energy; Drug leads; Oral bioactivity score;
License, permitting distribution, Pharmacokinetics; Docking
and reproduction in any medium,
provided the original work is
properly cited.
Publisher’s Note: AccScience
Publishing remains neutral with 1. Introduction
regard to jurisdictional claims in
published maps and institutional Malaria, a significant infectious disease characterized by acute febrile illness, continues
affiliations. to pose a global health concern. The World Health Organization estimates that the global

Volume 7 Issue 1 (2024) 1 https://doi.org/10.36922/itps.0976