Antiplasmodial potential and safety evaluation of the ethanolic stem bark extract of Distemonanthus benthamianus Baill. (Leguminosae)

Ayisi, Felix; Mensah, Caleb Nketia; Borquaye, Lawrence Sheringham

doi:10.1016/j.sciaf.2021.e00809

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…Herbal remedies have existed in folkloric medicine for a long time [17][18][19]. Some of the plants used in such herbal remedies provide elegant structural scaffolds that can serve as lead compounds in drug discovery efforts.…”

Section: His41mentioning

confidence: 99%

Allosteric Modulation of the Main Protease (MPro) of SARS-CoV-2 by Casticin—Insights from Molecular Dynamics Simulations

et al. 2022

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Inhibition of the main protease (M pro ) of SARS-CoV-2 has been suggested to be vital in shutting down viral replication in a host. Most efforts aimed at inhibiting M Pro activity have been channeled into competitive inhibition at the active site, but this strategy will require a high inhibitor concentration and impressive inhibitor-M Pro binding affinity. Allosteric inhibition can potentially serve as an effective strategy for alleviating these limitations. In this study, the ability of antiviral natural products to inhibit M Pro in an allosteric fashion was explored with in silico techniques. Molecular docking revealed a strong interaction between casticin, an antiviral flavonoid, and M pro at a site distant from the active site. This site, characterized as a distal site, has been shown to have an interdependent dynamic effect with the active site region. M pro only, M pro -peptide (binary) and M pro -peptide-casticin (ternary) complexes were subjected to molecular dynamics simulations for 50 ns to investigate the modulatory activity of casticin binding on M pro . Molecular dynamic simulations revealed that binding of casticin at the distal site interferes with the proper orientation of the peptide substrate in the oxyanion hole of the active site, and this could lead to a halt or decrease in catalytic activity. This study therefore highlights casticin as a potential allosteric modulator of the SARS-CoV-2 main protease, which could be optimized and developed into a potential lead compound for anti-SARS-CoV-2 chemotherapy.

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Section: His41mentioning

confidence: 99%

Allosteric Modulation of the Main Protease (MPro) of SARS-CoV-2 by Casticin—Insights from Molecular Dynamics Simulations

et al. 2022

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“…However, the protozoans have developed resistance against many of the current therapies and this has led to the exploration of various other sources for potential malaria therapeutic agents [10]. In many indigenous African homes, plants have served as a mainstay for the treatment of malaria and malaria-like symptoms [11][12][13][14][15]. In fact, it is estimated that over 70% of the global population uses plantbased products for their healthcare needs [16].…”

Section: Introductionmentioning

confidence: 99%

An In Silico Study of the Interactions of Alkaloids from Cryptolepis sanguinolenta with Plasmodium falciparum Dihydrofolate Reductase and Dihydroorotate Dehydrogenase

Kyei

Gasu

Ampomah

et al. 2022

Journal of Chemistry

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The Plasmodium falciparum dihydrofolate reductase (PfDHFR) and dihydroorotate dehydrogenase (PfDHODH) are essential for Plasmodium falciparum growth and development, and have been validated as targets for the development of new antimalarial agents. Several alkaloids isolated from Cryptolepis sanguinolenta have been reported to have antiplasmodial activity, but their protein targets are unknown. Therefore, molecular docking and molecular dynamics simulations were used to investigate the interactions and stability of the alkaloids with PfDHFR and PfDHODH. Based on physicochemical characteristics, alkaloids were grouped as sterically bulky (sb) or planar (pg). Docking results revealed strong binding affinities (−6.0 to −13.4 kcal/mol) of the alkaloids against PfDHODH and various strains of PfDHFR while interacting with key residues such as Asp54 and Phe58 in PfDHFR. The pg alkaloids had high binding affinity and preference for the inhibitor binding domain over the flavin mononucleotide (FMN) binding domain in PfDHODH due to size considerations. From the molecular dynamics trajectories, protein-alkaloid complexes were stable throughout the simulation, with supporting evidence from root mean square deviations, root mean square fluctuations, radius of gyration, free binding energies, and other parameters. We report herein that biscryptolepine and cryptomisrine (sb class), as well as cryptolepinone, cryptoheptine, cryptolepine, and neocryptolepine (pg class), are capable of inhibiting PfDHFR effectively in pyrimethamine sensitive and resistant cells. Also, our results show that alkaloids of the pg class can inhibit PfDHODH as FMN decoys, as well as direct enzyme inhibitors, thereby halting crucial protein function.

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Oplodiol and nitidine as potential inhibitors of Plasmodium falciparum dihydrofolate reductase: insights from a computational study

Akakpo,

Gasu,

Mensah

et al. 2023

Journal of Biomolecular Structure and Dynamics

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Antiplasmodial potential and safety evaluation of the ethanolic stem bark extract of Distemonanthus benthamianus Baill. (Leguminosae)

Cited by 6 publications

References 30 publications

Allosteric Modulation of the Main Protease (MPro) of SARS-CoV-2 by Casticin—Insights from Molecular Dynamics Simulations

Allosteric Modulation of the Main Protease (MPro) of SARS-CoV-2 by Casticin—Insights from Molecular Dynamics Simulations

An In Silico Study of the Interactions of Alkaloids from Cryptolepis sanguinolenta with Plasmodium falciparum Dihydrofolate Reductase and Dihydroorotate Dehydrogenase

Oplodiol and nitidine as potential inhibitors of Plasmodium falciparum dihydrofolate reductase: insights from a computational study

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