Novel 1, 3, 4-Oxadiazole-pyridine hybrids as potential DNA gyrase B inhibitors (5D7R): ADMET prediction and molecular docking study
Abstract
A small molecule (ligand) is placed in the binding site of its macromolecular target (receptor) using a computational process called molecular docking, which also calculates the binding affinity of the small molecule. With the use of PyRx software, the current study tried a high-throughput in-silico screening of 16 compounds docked with the crystal structure of DNA gyrase B receptors (PDB ID: 5D7R). In the range of -8.0 and -8.1, 3 of these 16 compounds displayed very good mol dock scores. As a typical medicine, amoxicillin medications have a mol dock score of -7.1. According to the results, all of the investigated ligands occupy similar positions and directions within the putative binding site of DNA gyrase B receptors (PDB ID: 5D7R), which reveals a sizable area surrounded by a membrane binding domain that acts as a pathway for substrate entry into the active site. Additionally, any small molecule's affinity can be viewed as a special instrument in the field of drug design and provide a possibility for future study to create an antibacterial activity. Additionally, ADME evaluations must be used to confirm compounds that are candidates for oral administration. The findings demonstrated that compound 4a, 4b, 4c, 4d, 4i, 4j, and 4k absorbed from GIT and compound 4i, 4j, and 4k fulfilled the Lipinski rule.
Keywords: 1, 3, 4-Oxadiazole, ADME Evaluation, molecular docking, antimicrobial activity
Keywords:
1, 3, 4-Oxadiazole, ADME Evaluation, molecular docking, antimicrobial activity
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References
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2. Jangra S, Kumar S, Choudhary M. Molecular docking studies of 1, 3, 4 oxadiazoles Derivatives as anti-convulsive agents. World Journal of Advanced Research and Reviews. 2020; 8(1):151-79. https://doi.org/10.30574/wjarr.2020.8.1.0381
3. Yurttaş L, Bülbül EF, Tekinkoca S, Demirayak Ş. Antimicrobial activity evaluation of new 1,3,4-oxadiazole derivatives. Acta Pharm Sci. 2017; 55(2):45-54. https://doi.org/10.23893/1307-2080.APS.05511
4. Macaev, F.et al., R: Synthesis of Novel 5-aryl-2- thio-1,3,4-oxadiazoles and the Study of Their Structure-Anti-Mycobacterial Activities Bioorg Med Chem 2005; 13:4842. https://doi.org/10.1016/j.bmc.2005.05.011
5. Abd-Ellah SH, Abdel-Aziz M, Shoman ME, Beshr EAM, Kaoud TS, Ahmed ASFF. New 1,3,4- oxadiazole/oxime hybrids: Design, synthesis, anti-inflammatory, COX inhibitory and ulcerogenic liability. Bioorg Chem. 2017; 74:15- 29. https://doi.org/10.1016/j.bioorg.2017.06.003
6. Zou, X. J.; Lai, L. H.; Jin, G. Y.; Zhang, Z. X. Synthesis, Fungicidal Activity, and 3D-QSAR of Pyridazinone-Substituted 1,3,4-oxadiazoles and 1,3,4-thiadiazoles J Agric Food Chem 2002; 50:3757 https://doi.org/10.1021/jf0201677
7. Palaska E, Sahin G, Kelicen, P Durlu N. T, Altinok, G. Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4- oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones. Farmacoterapia 2002; 57:101. https://doi.org/10.1016/S0014-827X(01)01176-4
8. Bajaj S, Roy PP, Singh J. Synthesis, thmynidine phosphorylase inhibitory and computational study of novel 1,3,4-oxadizole-2-thione derivatives as a potential anticancer agent. Comput Biol Chem. 2018; 74:151-160. https://doi.org/10.1016/j.compbiolchem.2018.05.013
9. Ryng S, Zimecki M, Jezierska-Mazzarello A, Panek JJ, Mączyński M, et al. A complex study of 5-amino-3-methyl-4-[2-(5-amino-1,3,4- oxadiazolo)]-isoxazole monohydrate: A new low-molecular-weight immune response modifier. Journal of Molecular Structure 2011; 999:60-67. https://doi.org/10.1016/j.molstruc.2011.05.031
10. Zarghi A, Tabatabai S. A, Faizi M, Ahadian A, Navabi P, Zanqaneh V, Shafiee A. Z. Synthesis and Anticonvulsant Activity of New 2- substituted-5-(2-benzyloxyphenyl)-1,3,4- oxadiazoles. Bioorg Med Chem Lett 2005; 15:863 https://doi.org/10.1016/j.bmcl.2005.02.014
11. Khan M. T, Choudhary M. I, Khan K. M, Rani M, Atta‐ur‐Rahman. Structure-activity Relationships of Tyrosinase Inhibitory Combinatorial Library of 2,5-disubstituted-1,3,4- oxadiazole Analogues. Bioorg Med Chem 2005; 13:3385 https://doi.org/10.1016/j.bmc.2005.03.012
12. Ibrahim TS, Almalki AJ, Moustafa AH, Allam RM, Abuo-Rahma GE, El Subbagh HI, Mohamed MF. Novel 1, 2, 4-oxadiazole-chalcone/oxime hybrids as potential antibacterial DNA gyrase inhibitors: Design, synthesis, ADMET prediction and molecular docking study. Bioorganic Chemistry. 2021 Jun 1; 111:104885. https://doi.org/10.1016/j.bioorg.2021.104885
13. Jadhav GR, Deshmukh DG, Medhane VJ, Gaikwad VB, Bholay AD. 2, 5-Disubstituted 1, 3, 4-oxadiazole derivatives of chromeno [4, 3-b] pyridine: Synthesis and study of antimicrobial potency. Heterocyclic Communications. 2016 Jun 1; 22(3):123-30. https://doi.org/10.1515/hc-2015-0215
14. Gaonkar SL, Rai KL, Prabhuswamy B. Synthesis and antimicrobial studies of a new series of 2-{4-[2-(5-ethylpyridin-2-yl) ethoxy] phenyl}-5-substituted-1, 3, 4-oxadiazoles. European journal of medicinal chemistry. 2006 Jul 1; 41(7):841-6. https://doi.org/10.1016/j.ejmech.2006.03.002
15. Farghaly AA, Vanelle P, El-Kashef HS. Synthesis, reactions and antimicrobial activity of some new 1, 3, 4-oxadiazoles, 1, 2, 4-triazoles and 1, 3, 4-thiadiazines derived from pyrazole. Heterocyclic Communications. 2005 Aug 1; 11(3-4):255-62. https://doi.org/10.1515/HC.2005.11.3-4.255
16. Aghekyan АА, Mkryan GG, Panosyan HA, Safaryan AS, Stepanyan HM. Synthesis and Antibacterial Activity of Novel (4-Methoxyphenyl)-tetrahydropyranyl-substituted 1, 3, 4-Oxadiazoles. Russian Journal of Organic Chemistry. 2020 Feb; 56:281-6. https://doi.org/10.1134/S1070428020020177
17. Bakavoli M, Rahimizadeh M, Shiri A, Eshghi H, Vaziri-Mehr S, Pordeli P, Nikpour M. Synthesis and evaluation of antibacterial activity of new derivatives of pyrimido [4, 5-e][1, 3, 4] oxadiazine. Heterocycl. Commun., 2011; 17(1-2):49-52. https://doi.org/10.1515/hc.2011.009
18. Ningaiah S, Bhadraiah UK, Doddaramappa SD, Keshavamurthy S, Javarasetty C. Novel pyrazole integrated 1, 3, 4-oxadiazoles: Synthesis, characterization and antimicrobial evaluation. Bioorganic & medicinal chemistry letters. 2014 Jan 1; 24(1):245-8. https://doi.org/10.1016/j.bmcl.2013.11.029
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Durgadasheemi NN, Kolageri SN. Novel 1, 3, 4-Oxadiazole-pyridine hybrids as potential DNA gyrase B inhibitors (5D7R): ADMET prediction and molecular docking study. JDDT [Internet]. 15Mar.2023 [cited 22Mar.2023];13(3):12-9. Available from: https://jddtonline.info/index.php/jddt/article/view/5749
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