IIARD International Institute of Academic Research and Development

INTERNATIONAL JOURNAL OF CHEMISTRY AND CHEMICAL PROCESSES (IJCCP )

E-I SSN 2545-5265
P- ISSN 2695-1916
VOL. 10 NO. 5 2024
DOI: 10.56201/ijccp.v10.no5.2024.pg65.91

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Quantitative Structural Activity Relationship (QSAR), Density Functional Theory (DFT), Molecular Docking, ADMET and Target Prediction Studies of Antimalarial activity of 1,2,4-triazolo[,-a]pyrazine derivatives against Resistant Plasmodium Falciparum

Olatunji Nathaniel Oladoye, Oladuji Tofunmi Emmanuel, Olatunde Abimbola Modupe, Asibor Yemisi Elizabeth and Semire Banjo

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Abstract

Quantum Chemical Methods via Density Functional Theory (DFT), Quantitative Structure Activity Relation (QSAR) and docking methods were used to observed the anti- malaria activity of 1,2,4-triazolo[4,3-a] pyrazine derivatives. Many descriptors including dipole moment (DM), hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), hydrophobicity (LogP), energy gap (?Eg), chemical hardness (?), softness, and chemical potential (?) energies were calculated. All the five QSAR models were validated and the results showed that R-squared (R2), adjusted R² (R²adj), cross-validation (Q²), standard error of estimation (SEE) and mean absolute error (MAE) ranged from 0.9457 – 0.9902, 0.9225 – 0.9861, 0.8917 – 0.9789, 0.0687 – 0.1621, and 0.0676 – 0.01190, respectively, indicating that all the models have good predictability. However, models 1 (with R2 = 0.9902, R²adj = 0.9861, Q² = 0.9789, SEE = 0.0687 and MAE = 0.0676) was used to predict new set of triazolo[4,3-?] pyrazine due to its statistical robustness. The docking results of the six predicted triazolo[4,3- ?] pyrazine compounds (NLs) and the standard drugs (Artesunate, Puromycin, and Pyrimethamine) against Plasmodium falciparum (PfMyoA) with PDB ID 6YCX, 6YCY, and 6YCZ revealed the binding affinities range of -7.80 to -9.30 kcal/mol for 6YCX, -7.60 to -9.30 kcal/mol for 6YCY and -7.90 to -9.00 kcal/mol for 6YCZ. The binding affinities of Artesunate, Puromycin and Pyrimethamine are -7.70, -7.90 and -6.60 kcal/mol for 6YCX, -7.50, -8.20 and -6.40 kcal/mol for 6YCY, -8.00, -8.30 and -6.70 kcal/mol, respectively, indicating that NL7, NL8, NL9, NL10 and NL18 have outstanding binding affinity than the selected drugs. The ADMET profiles, the computational QSAR study together with the molecular docking has actually provided a valuable approach for researchers to developed model, making it possible to p

keywords:

1,2,4-triazolo[4,3-a] pyrazine derivatives, DFT-QSAR, Molecular docking

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