Glucosamine-6-phosphate synthase inhibiting C3-β-cholesterol tethered spiro heterocyclic conjugates: Synthesis and their insight of DFT and docking study.

Authors:
Antony Stalin
Antony Stalin
Loyola College
India
Natarajan Arumugam
Natarajan Arumugam
College of Science
College Station | United States
Raju Suresh Kumar
Raju Suresh Kumar
College of Science
Malaysia
Mostafizur Rahaman
Mostafizur Rahaman
College of Science

Bioorg Chem 2019 Apr 9;88:102920. Epub 2019 Apr 9.

Department of Chemistry, College of Science, King Saud University, Riyadh, Saudi Arabia. Electronic address:

A series of novel covalent cholesterol-spiro pyrrolidine/pyrrolizidine heterocyclic hybrids possessing biologically active oxindole, indanedione, and acenaphthylene-1-one have been synthesized by the reaction of C3-β-cholesteroalacrylate with heterocyclic di- and tri-ketones. All the sixteen compounds were obtained as a single isomer in good yield through a stereo- and regio- selective 1,3-dipolar cycloaddition methodology. Stereochemistry of the spiranic cycloadducts has been established by spectroscopic analysis and the regioselectivity outcome of the spiro adducts has been accomplished by DFT calculations at B3LYP/6-31G (d,p) level study. In vitro antibacterial activity of the newly synthesized cycloadducts were evaluated against highly pathogenic Gram-positive and Gram-negative bacteria and the most active compounds 5a, 13, and 14 underwent automated in silico molecular docking analysis in order to validate their effective orientation as a inhibitors bound in the active site of glucosamine-6-phosphate synthase (1XFF) enzyme by employing AutoDock Tools.

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http://dx.doi.org/10.1016/j.bioorg.2019.102920DOI Listing
April 2019
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