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INNOSC Theranostics and
Pharmacological Sciences Docking study of quinoline-3-carbaldehyde derives

Figure 7C reveals that compound A5 exhibits notable except Lys7. This suggests that it has good water–lipid
hydrophobic interactions with all observed binding residues, interface transport properties within the cell membrane
except for Lys7. This observation suggests that compound of the Pf HAP protein. In addition, the quinoline core of
A5 may possess favorable water–lipid interface transport compound A5 had better solvent accessibility, indicating
properties, facilitating its movement across the cell membrane a more open conformation that facilitates binding with
of the Pf HAP protein. In addition, the quinoline core of reactive sites on the target residues. Based on our study
compound A5 demonstrates improved solvent accessibility, findings, compound A5 shows promise as a potential
indicating a more open conformation. This conformation candidate for developing drugs against antimalarial diseases.
may promote easier interaction with the reactive sites of the
target residues, as suggested by Gromiha and Ahmad . Acknowledgments
[36]
The binding interactions between the best reference None.
drug, mefloquine, and the residues of P. falciparum HAP
(Figures 8A and 8B) indicate that the trifluoro groups Funding
attached to position 6 in compound A31 and position 8 in This work was funded, in part, by the University of Lagos
mefloquine play a role in their enhanced activity. However, Central Research Committee (CRC No. 2015/25) and
unlike compound A31, mefloquine does not exhibit any Nigerian Government TetFund IBR (CRC/TETFUND/
hydrogen-bonding interactions, which could potentially No. 2018/016).
contribute to its lower binding energy.
Conflict of interest
Similarly, the solvent accessibility surface interaction
of compound A31 is greater than that of mefloquine, The authors declare they have no competing interests.
as indicated in Figure 8C, indicating a more favorable
interaction within the binding pocket of the HAP protein. Author contributions

4. Conclusion Conceptualization: Luqman A. Adams, Oluwole B.
Familoni
In this study, we conducted toxicity profile tests to evaluate Formal analysis: Oluwafemi S. Aina, Luqman A. Adams
the synthesized compound 5 and fifty hypothetical Investigation: Oluwafemi S. Aina, Adebayo J. Bello
compounds A1–A50 for their drug-likeness. The aim Methodology: Oluwafemi S. Aina, Adebayo J. Bello
was to identify lead drug candidates that can overcome Writing – original draft: Oluwafemi S. Aina, Luqman A.
resistance to current standard reference antimalarial Adams
drugs. Among the hypothetical compounds, nine showed Writing – review & editing: Luqman A. Adams, Oluwole B.
no toxicity to human cells. Familoni

Compounds A5 and A31 exhibited high bioactivity
as kinase inhibitors, nuclear receptor ligands, and Ethics approval and consent to participate
glycoprotein receptors GPCR. In addition, compound A5 Not applicable.
acted as an enzyme inhibitor, capable of binding to other
available sites on the HAP enzyme. It is hypothesized Consent for publication
that the interaction of ligands at the active site of HAP, Not applicable.
specifically the aspartate (Asp215) and histidine (His32)
residues, can be treated as therapeutic targets, due to Availability of data
their importance for parasite growth and virulence, for Not applicable.
developing effective inhibitors.
Interestingly, compound A31, with a binding energy of Further disclosure
−11.3 kcal/mol, did not show any evidence of interaction The paper has been uploaded to or deposited in a preprint
with Asp215 or His32. However, compound A5, with a server (Research Square): https://doi.org/10.21203/
binding energy of −11.2 kcal/mol, exhibited π-π stacking rs.3.rs-2748975/v1
interactions with His32. The best-performing reference
drug, mefloquine, also did not show any interaction with References
Asp215 or His32.
1. World Health Organization, 2022, WHO Guidelines for
Furthermore, compound A5 displayed significant Malaria. WHO/UCN/GMP/2022.01 Rev. 2. Geneva: World
hydrophobic interactions with all observed binding residues, Health Organization.

Volume 7 Issue 1 (2024) 13 https://doi.org/10.36922/itps.0976