Antimalarial drug discovery against malaria parasites through haplopine modification: An advanced computational approach

Abstract

The widespread emergence of antimalarial drug resistance has created a major threat to public health. Malaria is a life‐threatening infectious disease caused by Plasmodium spp., which includes Apicoplast DNA polymerase and Plasmodium falciparum cysteine protease falcipain‐2. These components play a critical role in their life cycle and metabolic pathway, and are involved in the breakdown of erythrocyte hemoglobin in the host, making them promising targets for anti‐malarial drug design. Our current study has been designed to explore the potential inhibitors from haplopine derivatives against these two targets using an in silico approach. A total of nine haplopine derivatives were used to perform molecular docking, and the results revealed that Ligands 03 and 05 showed strong binding affinity compared to the control compound atovaquone. Furthermore, these ligand‐protein complexes underwent molecular dynamics simulations, and the results demonstrated that the complexes maintained strong stability in terms of RMSD (root mean square deviation), RMSF (root mean square fluctuation), and Rg (radius of gyration) over a 100 ns simulation period. Additionally, PCA (principal component analysis) analysis and the dynamic cross‐correlation matrix showed positive outcomes for the protein‐ligand complexes. Moreover, the compounds exhibited no violations of the Lipinski rule, and ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions yielded positive results without indicating any toxicity. Finally, density functional theory (DFT) and molecular electrostatic potential calculations were conducted, revealing that the mentioned derivatives exhibited better stability and outstanding performance. Overall, this computational approach suggests that these haplopine derivatives could serve as a potential source for developing new, effective antimalarial drugs to combat malaria. However, further in vitro or in vivo studies might be conducted to determine their actual effectiveness.

Novel Insights in the Hypertension Treatment & Type 2 Diabetics Induced by Angiotensin Receptor Blockers: MD Simulation Studies & Molecular Docking of Some Promising Natural Therapies

“…They have the highest score against the Angiotensin II receptor of any investigated ligand due to two more hydrogen bonds with residues Arg67, Tyr87, and Cys180, among other considerations. Moreover, hydrogen bonds predominated, indicating that the compounds interacted strongly with the receptor. , In particular, this is the first time that the docking interaction between these naturally occurring substances and the Angiotensin II receptor to accomplish the aforementioned biological activity as an antihypertensive has been identified.…”

“…Moreover, hydrogen bonds predominated, indicating that the compounds interacted strongly with the receptor. 42,43 In particular, this is the first time that the docking interaction between these naturally occurring substances and the Angiotensin II receptor to accomplish the aforementioned biological activity as an antihypertensive has been identified.…”

Analysis of some flavonoids for inhibitory mechanism against cancer target phosphatidylinositol 3-kinase (PI3K) using computational tool

“…For example, the arrangement, substitution, and total number of hydroxyl groups significantly influence numerous mechanisms of antioxidant activity, including the ability to scavenge free radicals and chelate metal ions ( Ul Islam et al, 2021 ). Flavonoids have shown strong anticancer properties against different components in the PI3K/Akt/mTOR pathway ( Rehan et al, 2020 ; Zughaibi et al, 2021 ; Akash et al, 2023 ; AlZahrani et al, 2023 ). The scientific evidence supports the use of flavonoids as an adjuvant in radiation and other conventional therapeutic medications, in addition to their possible use as therapeutic agents against various cancers ( Ahmad et al, 2013 ).…”

Unveiling a novel terpolymer-metal complex: A detailed exploration of synthesis, characterization, and its potential as an antimicrobial and antioxidant agent

“…These activities are probably brought on by the presence of -N-H, –C S, groups [ [10] , [11] , [12] , [13] , [14] , [15] ]. Ahamad et al reported a new class of metal chelated polyurea for its excellent antimicrobial activity against S. aureus, E. coli, B. subtilis , and S. typhi [ [16] , [17] , [18] , [19] , [20] ]. Azo series based on transition metal complexes (Cu 2+ , Zn 2+ , Mn 2+ , Co 2+ and Ni 2+ ) were screened for their antibacterial and antifungal activities against S. aureus, E. coli and A. niger and C. albicans [ 21 ].…”