Document Type : Original Research Article


Computational and Organic Chemistry group, Department of Science Laboratory Technology, The Oke-Ogun Polytechnic Saki, P.M.B 021, Saki, Oyo State, Nigeria



Inhibitory activities of five derivatives of 1,2,3-triazole and isoxazole-linked pyrazole hybrids (A,B,C,D and D) were investigated on two bacteria cell lines E.coli (5R1R) and S.aureous (2XCT) to predict their potency and their use as antibacterial agents. Spartan’14 was used to optimized the compounds via Density functional theory to calculate the molecular descriptors of the studied ligands and a standard drug (Amoxicillin). All the ligands obey Lipinski rule except ligand E with higher molecular weight greater than 500g/mol. The band gap which explained the stability of the ligand-protein complex formed were observed to be lower than the standard with outstanding lower band gap from Ligand B and E, hence this two ligand is expected to have higher stability as compared to other ligands and the standard drug. The predicted affinities via docking studies for E.coli were -7.3kcal/mol, -8.5kcal/mol, -7.5kcal/mol, -7.9kcal/mol, -8.9 kcal/mol and S.aureous were -6.9kcal/mol, -7.8kcal/mol, -7.0kcal/mol, -7.5kcal/mol. -7.3kcal/mol for Ligand A, B, C, D and E respectively. Also a standard drug (Amoxicillin) was also subjected to docking studies with the two receptor. However, the two ligands gave better inhibition at the active site of the two protein as compared to the standard drug with higher affinities from Ligand B, D and E. In addition, ADMET properties of the ligands displayed that all the ligands could be better absorbed from the intestinal tract when administered orally with no toxicity and they are not easily undergo biodegradation. Therefore, the ligands are good drug candidate which could be considered for clinical trials.

Graphical Abstract

Theoretical Studies of 1, 2, 3-Triazole and Isoxazole-Linked Pyrazole Hybrids as Antibacterial Agents: An Approach of Docking and Density Functional Theory


Main Subjects

[1] S.A. Akintelu, E.A. Erazua, A.S. Folorunso, Theoretical and experimental investigations on the antibacterial activities of Garcinia Kola seed. J Chem Pharm Res 11(2019)38–44.
[2] Z.N. Larbi, S. Farida, L. Hocine, O. Ahmed, G.N.W. Joice, M. Filippo, Chemical composition and antibacterial activity of essential oils from the algerian endemic Origanumglandulosum Desf against Multidrug- Resistant Uropathogenic E. coli Isolates. Antibiotics 15(2020) 9-29.
[3] J.J. Liu,  M.Y. Zhao, X. Zhang, X. Zhao, H.L. Zhu, Pyrazole derivatives as antitumor, anti-inflammatory and antibacterial agents. Med Chem 13(2013) 1957–66.
[4] P.C. Miller, J.M. Molyneaux,  One-pot synthesis of dimethyl [1- substituted-5-hydroxy-1H-pyrazol-4-yl]phosphonates. Org Prep ProcedInt 31 (1999) 295–304.
[5] J.B. Sperry, D.I. Wright, Furans, thiophenes and related heterocycles in drug discovery. CurrOpin Drug Discovery Dev 10 (2005) 723.
[6] S. Maloy, M. Schaechter , The era of microbiology: a golden phoenix. IntMicrobiol , 9(2006) 1–7.
[7] J.K. Fredrickson, JM. Zachara, D.L. Balkwill, D. Kennedy, S.M. Li, H.M. Kostandarithes, M.J. Daly, M.F. Romine, F.J. Brockman, Geomicrobiology of high-level nuclear waste-contaminated vadose sediments at the Hanford site, Washington state. Appl Environ Microbiol 70(2004) 4230–4241.
[8] E.Y. Garoy, Y.B. Gebreab, O.O. Achila, D.G. Tekeste, R. Kesete, R. Ghirmay, R. Kiflay, T. Tesfu,  Methicillin-Resistant Staphylococcus aureus (MRSA): Prevalence and Antimicrobial Sensitivity Pattern among Patients-A Multicenter Study in Asmara, Eritrea. Can. J. Infect. Dis. Med. Microbiol. 17(2019) 490-508.
[9] A.D. Becke, Density‐functional thermochemistry. III. The role of exact exchange J. Chem. Phy.98 (1993), 1372-1377.
[10] A.K. Oyebamiji, I.O. Abdulsalami, B. Semire, Dataset on Insilicoapproaches for 3,4-dihydropyrimidin-2(1H)-one urea derivatives as efficient Staphylococcus aureusinhibitor. Data in Brief 32 (2020) 106195
[11] Protein data bank (2015)
[12] O. Trott, A. Olson, AutoDockVina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry. 31(2010) 455-461.
[13] DS. BIOvIA, Discovery studio modeling environment. San Diego. DassaultSystemes, Release, 4(2017) 274 – 286.
[14]W.L. DeLano, Pymol: An open-source molecular graphics tool. CCP4 Newsletter. 40(2002) 82-92.
[15] P.W. Atkins, P.W, Physical chemistry, Oxford University press, Oxford, 263 (1986).
[16] S. Jie, C. Feixiong, X. You, L. Weihua, T. Yun, Estimation of ADME properties with substructure pattern recognition. J ChemInf Model 50 (2010) 1034–1041.
[17] B. Semire, A.K. Oyebamiji, O.A. Odunola, Electronic properties’ modulation of D–A–A via fluorination of 2-cyano-2-pyran-4-ylidene-acetic acid acceptor unit for efficient DSSCs: DFTTDDFT approach. SciAfr 7(2020) e00287
[18] K.A Oyebamiji, B. Semire, Studies of 1, 4-dihydropyridine derivatives for anti-breast cancer (MCF-7) activities: combinations of DFT-QSAR and docking methods. N Y Sci J 9(2016)58–66.
[19] A.B. Adegoke, T.M. Oyelowo, J.D. Sanusi, Computational Studies of 1, 2, 3- Triazoles Derivatives against Yellow Fever Virus: DFT-Based. European Modern Journal Studies. 4(2020) 94-103.
[20] A.K. Oyebamiji, G.F. Tolufashe, B. Semire, Inhibition study on anti-type 3 of 3 α-hydroxysteroid dehydrogenase activity against 1,2,3-triazolo[4,5-D]pyrimidine derivatives: molecular modelling approach. Sci Afr 8 (2020) e00444
[21] I.A. Adejoro, S.O. Waheed, O.O. Adeboye, Molecular Docking Studies of Lonchocarpuscyanescens Triterpenoids as Inhibitors for Malaria. Journal of Physical Chemistry Biophysics. 6(2016) 16-21.
[22] O. Mebarka, B. Salah, L. Khaled, D. Ismail, B. Houmam, Molecular docking studies and ADMET properties of new 1.2.3 triazole derivatives for anti-breast cancer activity. J Bionanosci 12 (2018) 1–11.