Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase

Aliyu Wappah Mahmud; Muhammad Tukur Ibrahim; Usman Abdullahi; Ahmad Mustapha

Research Article

Year 2025, Volume: 9 Issue: 2, 33 - 43

Aliyu Wappah Mahmud , Muhammad Tukur Ibrahim , Usman Abdullahi , Ahmad Mustapha

Abstract

References

[1] cöçvmöxçcmvişl
[2] ipo3ğproi

Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase

Year 2025, Volume: 9 Issue: 2, 33 - 43

Aliyu Wappah Mahmud , Muhammad Tukur Ibrahim , Usman Abdullahi , Ahmad Mustapha

Abstract

Management and control of malaria remain challenging due to the continuous emergence of drug resistant and the adaptive nature of the mosquito vector. This necessitates the continuous discovery of potent antimalaria drugs. Lactate dehydrogenase from Plasmodium falciparum (PfLDH) is an essential catalyst for the parasite’s energy production. PfLDH is a significant target in the design and discovery of antimalarial drugs because its inhibition leads to the death of the parasite. In this work, fifteen 10-amidinobenzonaphthyridine molecules active against Chloroquine-sensitive and Chloroquine-resistant strains of P. falciparum were screened through molecular docking with the view to find lead inhibitor of PfLDH. The binding affinities of the compounds ranged from -5.5 to -7.8kcal/mol. The compound with the highest binding affinity was modified and nine novel 10-amidinobenzonaphthyridines were designed. The designed compounds have better binding affinity toward the target ranging from -7.8 to -8.8kcal/mol and four of which have better binding affinities than Pyronaridine, a 10-amidinobenzonaphthyridine antimalaria drug. Furthermore, ADME properties of the designed compounds were predicted in silico and their drug-likeness investigated using Lipinski’s rule of five and Veber’s rule of two. Based on these rules, compound D1, D2, D3, D4, D5 and D8 are potential oral drug candidates. Compound D2, D3 and D8 have good binding affinities and ADME properties therefore, can be developed into potent antimalaria targeting PfLDH. The results of this work can be used to develop active antimalaria drug capable of inhibiting PfLDH.

Keywords

Molecular docking, 10-amidinobenzonaphthyridine, Plasmodium falciparum lactate dehydrogenase, ADME properties, in silico drug design

References

[1] cöçvmöxçcmvişl
[2] ipo3ğproi

There are 2 citations in total.

Details

Primary Language	English
Subjects	Physical Chemistry (Other)
Journal Section	Research Article
Authors	Aliyu Wappah Mahmud 0000-0003-0884-7890 Muhammad Tukur Ibrahim 0000-0002-6146-5667 Usman Abdullahi 0009-0006-5584-2311 Ahmad Mustapha 0009-0003-8165-1154
Early Pub Date	September 19, 2024
Publication Date
Submission Date	July 14, 2024
Acceptance Date	August 25, 2024
Published in Issue	Year 2025 Volume: 9 Issue: 2

Cite

APA	Mahmud, A. W., Ibrahim, M. T., Abdullahi, U., Mustapha, A. (2024). Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase. Turkish Computational and Theoretical Chemistry, 9(2), 33-43.
AMA	Mahmud AW, Ibrahim MT, Abdullahi U, Mustapha A. Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase. Turkish Comp Theo Chem (TC&TC). September 2024;9(2):33-43.
Chicago	Mahmud, Aliyu Wappah, Muhammad Tukur Ibrahim, Usman Abdullahi, and Ahmad Mustapha. “Molecular Docking Screening, in Silico Drug Design and ADME Prediction of 10-Amidinobenzonaphthyridines As Potent Inhibitors of Plasmodium Falciparum Lactate Dehydrogenase”. Turkish Computational and Theoretical Chemistry 9, no. 2 (September 2024): 33-43.
EndNote	Mahmud AW, Ibrahim MT, Abdullahi U, Mustapha A (September 1, 2024) Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase. Turkish Computational and Theoretical Chemistry 9 2 33–43.
IEEE	A. W. Mahmud, M. T. Ibrahim, U. Abdullahi, and A. Mustapha, “Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase”, Turkish Comp Theo Chem (TC&TC), vol. 9, no. 2, pp. 33–43, 2024.
ISNAD	Mahmud, Aliyu Wappah et al. “Molecular Docking Screening, in Silico Drug Design and ADME Prediction of 10-Amidinobenzonaphthyridines As Potent Inhibitors of Plasmodium Falciparum Lactate Dehydrogenase”. Turkish Computational and Theoretical Chemistry 9/2 (September 2024), 33-43.
JAMA	Mahmud AW, Ibrahim MT, Abdullahi U, Mustapha A. Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase. Turkish Comp Theo Chem (TC&TC). 2024;9:33–43.
MLA	Mahmud, Aliyu Wappah et al. “Molecular Docking Screening, in Silico Drug Design and ADME Prediction of 10-Amidinobenzonaphthyridines As Potent Inhibitors of Plasmodium Falciparum Lactate Dehydrogenase”. Turkish Computational and Theoretical Chemistry, vol. 9, no. 2, 2024, pp. 33-43.
Vancouver	Mahmud AW, Ibrahim MT, Abdullahi U, Mustapha A. Molecular docking Screening, in silico drug design and ADME prediction of 10-amidinobenzonaphthyridines as potent inhibitors of Plasmodium falciparum Lactate Dehydrogenase. Turkish Comp Theo Chem (TC&TC). 2024;9(2):33-4.