Analogues of Dipicolinic acid, Phenanthroline, and N-ethylmaleimide as Potential Inhibitors of Plasmodium falciparum falcilysin

Abduljabbar I. Dankani1, Suleiman Aminu2*, Umar SaiduMukhtar J. Ladan1
1Department of Biochemistry, Usmanu Danfodiyo University, Sokoto, Nigeria
2Department of Biochemistry, Ahmadu Bello University, Zaria, Nigeria

Corresponding Author: [email protected], [email protected]; Tel: +2347064487381
Recieved Date: 15 January 2022; Accepted Date: 22 April 2022; Published Date: 03 May
Citation: Dankani AI, Aminu S, Saidu U, Ladan MJ. Analogues of Dipicolinic acid, Phenanthroline, and N-ethylmaleimide as Potential Inhibitors of Plasmodium falciparum falcilysin. Trop J Nat Prod Res. 2022; 6(4): 621-627. http://www.doi.org/10.26538/tjnpr/v6i4.25
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© 2022 Dankani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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ABSTRACT

In a bid to meet its amino acid requirements, Plasmodium falciparum utilizes falcilysin (in addition to other proteases) to aid in cleaving the host hemoglobin at the polar residues. The dependence of the parasite on the host hemoglobin could lead to increased disease severity in the host. In this study, molecular docking analyses were used to evaluate the binding interactions of dipicolinic acid, phenanthroline, and N-ethylmaleimide analogues to P. falciparum falcilysin.  The protein databank and the CheBI database were used to find P. falciparum falcilysin and the compounds, respectively. The protein and the collected compounds were imported into PyRx virtual screening software and the docking was initiated. Following that, Discovery Studio was utilized to virtualize the 2D and 3D interactions. The binding energies of 4,7-diphenyl-1,10-phenanthroline 4,4-disulfonate and 4,7-diphenyl-1,10-phenanthroline 4,4-disulfonic acid were both more than -10.0 kcal/mol among the phenanthroline analogues while only oleanolic acid and N-ethylsuccinimide-mycothiol conjugate from the dipicolinic acid and N-ethylmaleimide analogues had binding energies of -9.7 and -9.4 kcal/mol respectively. The higher binding energies were attributable to hydrogen bond interactions as well as other interactions between the chemicals and the amino acid residues of the falcilysin. The analogues were shown to be moderately safe in pharmacokinetic investigations and scaled Lipinskis rule of five (RO5). The findings of the study revealed that analogues of dipicolinic acid, phenanthroline, and N-ethylmaleimide could serve as potential inhibitors of P. falciparum falcilysin. Thus, the compounds can be used as leads or structural scaffolds against the enzyme.

Keywords: Dipicolinic acid, Falcilysin, N-ethylmaleimide, P. falciparum, Phenanthroline.
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ISSN: 2616-0684 (Print)
ISSN: 2616-0692 (Online)
DOI: 10.26538/tjnpr
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