Exploring the inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated quorum sensing utilizing QSAR and docking

Sisir Nandi; Mohit Kumar; Rashmi Kumari; Aaruni Saxena

doi:10.33393/dti.2022.2512

Authors

Sisir Nandi Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Kashipur - India https://orcid.org/0000-0002-9960-6584
Mohit Kumar Department of Pharmacy, Vivek College of Technical Education, Bijnor - India https://orcid.org/0000-0001-8975-7613
Rashmi Kumari Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Kashipur - India https://orcid.org/0000-0002-9935-1227
Aaruni Saxena Department of Cardiovascular Medicine, University of Nottingham, Nottingham - UK https://orcid.org/0000-0002-0649-2929

DOI:

https://doi.org/10.33393/dti.2022.2512

Keywords:

Antimicrobial resistance, Indazole compounds, Molecular docking, QSAR, Quorum sensing,, SAH/MTAN

Abstract

The world is under the great threat of antimicrobial resistance (AMR) leading to premature deaths. Microorganisms can produce AMR via quorum sensing mechanisms utilizing S-adenosyl homocysteine/methylthioadenosine nucleosidase (SAH/MTAN) biosynthesis. But there is no specific drug developed to date to stop SAH/MTAN, which is a crucial target for the discovery of anti-quorum sensing compound. It has been shown that indazole compounds cause inhibition of SAH/MTAN-mediated quorum sensing, but the biochemical mechanisms have not yet been explored. Therefore, in this original research, an attempt has been made to explore essential structural features of these compounds by quantitative structure-activity relationship (QSAR) and molecular docking of indazole compounds having inhibition of SAH/MTAN-mediated quorum sensing. The validated QSAR predicted five essential descriptors and molecular docking helps to identify the active binding amino acid residues involved in ligand-receptor interactions that are responsible for producing the quorum sensing inhibitory mechanisms of indazole compounds against SAH/MTAN-mediated AMR.

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Author Biographies

Mohit Kumar, Department of Pharmacy, Vivek College of Technical Education, Bijnor - India

Department of Pharmacy, Vivek College of Technical Education, Bijnor, India

Aaruni Saxena, Department of Cardiovascular Medicine, University of Nottingham, Nottingham - UK

Department of cardiovascular medicine, University of Nottingham, United Kingdom

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