DESIGN, BINDING AFFINITY STUDIES AND IN SILICO ADMET PREDICTIONS OF NOVEL ISOXAZOLES AS POTENTIAL ANTI-BACTERIAL

Authors

  • G. CHAITANYA SAI Department of Pharmaceutical Chemistry, M. S. Ramaiah University of Applied Sciences, Bengaluru 560054, Karnataka, India
  • JUDY JAYS Department of Pharmaceutical Chemistry, M. S. Ramaiah University of Applied Sciences, Bengaluru 560054, Karnataka, India
  • BURHANUDDIN MADRIWALA Department of Pharmaceutical Chemistry, M. S. Ramaiah University of Applied Sciences, Bengaluru 560054, Karnataka, India

DOI:

https://doi.org/10.22159/ijcpr.2022v14i4.2001

Keywords:

Molecular docking, DNA ligase, Topoisomerase, Glutamate racemase, Sterol Demethylase, Isoxazole, ADMET, SWISSPDB, PyMOL

Abstract

Objective: The objective of the study is to design novel isoxazole derivatives, predicting their interactions with the selected target proteins and determining the ADMET properties of potent molecules using recent computational methods.

Methods: With the intent to discover potent novel antibacterial, we have designed a set of compounds containing the isoxazole nucleus by using software tools like Discovery studios, PyRx, PyMOL, SWISSPDB. ADMET studies were carried out by using SWISS ADMET and pkCSM. Molecular docking studies were carried out on the target proteins of both gram-positive and gram negative bacteria in order to assesses binding affinity for the proteins.

Results: Designed scaffold was designed by Benzene Derivatives Tethered with 5(4-chloro-3-nitro phenyl-1-yl) isoxazole. All the derivatives were docked against the three proteins, namely DNA Ligase (PDB ID: 3PN1), Topoisomerase (PDB ID: 3TTZ), Sterol demethylase (PDB ID: 5FSA), The compound JJC3F has shown best binding score against DNA ligase, sterol demethylase protein. Further, compound JJC3A has shown a better binding affinity towards topoisomerase than the standard drugs.

Conclusion: Molecular Docking study indicates that isoxazole derivatives may be effective inhibitors for the different microbial proteins. Additionally, in silico ADMET studies predicts drug-like features. Hence, these compounds may be considered as leads and further investigation of their analogues may help in development of novel drugs for the treatment of microbial diseases.

Downloads

Download data is not yet available.

References

Sabe VT, Ntombela T, Jhamba LA, Maguire GEM, Govender T, Naicker T. Current trends in computer-aided drug design and a highlight of drugs discovered via computational techniques: a review. Eur J Med Chem. 2021;224:113705. doi: 10.1016/j.ejmech.2021.113705, PMID 34303871.

Joseph L, George M. Anti-bacterial and in vitro anti-diabetic potential of novel isoxazole derivatives. Br J Pharm Res. 2016;9(4):1-7. doi: 10.9734/BJPR/2016/21926.

Aktas DA, Akinalp G, Sanli F, Yucel MA, Gambacorta N, Nicolotti O. Design, synthesis and biological evaluation of 3,5-diaryl isoxazole derivatives as potential anticancer agents. Bioorg Med Chem Lett. 2020;30(19):127427. doi: 10.1016/j.bmcl.2020.127427, PMID 32750679.

Shahinshavali S, Sreenivasulu R, Guttikonda VR, Kolli D, Rao MVB. Synthesis and anticancer activity of amide derivatives of 1,2-isoxazole combined 1,2,4-thiadiazole. Russ J Gen Chem. 2019;89(2):324-9. doi: 10.1134/S1070363219020257.

Bhardwaj S, Bendi A, Singh L. A study on synthesis of chalcone derived-5-membered isoxazoline and isoxazole scaffolds. Curr Org Synth. 2022;19. doi: 10.2174/ 1570179419666220127143141.

Bi F, Ma R, Ma S. Discovery and optimization of NAD+-dependent DNA ligase inhibitors as novel antibacterial com-pounds. Curr Pharm Des. 2017;23(14):2117-30. doi: 10.2174/1381612822666161025145639, PMID 27784238.

Sherer BA, Hull K, Green O, Basarab G, Hauck S, Hill P. Pyr-rolamide DNA gyrase inhibitors: optimization of antibacterial activity and efficacy. Bioorg Med Chem Lett. 2011;21(24):7416-20. doi: 10.1016/j.bmcl.2011.10.010, PMID 22041057.

Pires D; 2022. Biosig.unimelb.edu.au. Available from: http://biosig.unimelb.edu.au/pkcsm/theory. [Last accessed on 23 May 2022]

Shaik A, Bhandare RR, Palleapati K, Nissankararao S, Kanchar-lapalli V, Shaik S. Antimicrobial, antioxidant, and anticancer ac-tivities of some novel isoxazole ring containing chalcone and dihydro pyrazole derivatives. Molecules. 2020;25(5):1047. doi: 10.3390/molecules25051047, PMID 32110945.

Published

15-07-2022

How to Cite

SAI, G. C., J. JAYS, and B. MADRIWALA. “DESIGN, BINDING AFFINITY STUDIES AND IN SILICO ADMET PREDICTIONS OF NOVEL ISOXAZOLES AS POTENTIAL ANTI-BACTERIAL”. International Journal of Current Pharmaceutical Research, vol. 14, no. 4, July 2022, pp. 74-77, doi:10.22159/ijcpr.2022v14i4.2001.

Issue

Section

Original Article(s)