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

Periyasami, Govindasami and Kamalraj, Subban and Padmanaban, Ramanathan and Kumar, Santhakumar Yeswanth and Stalin, Ntony and Arumugam, Natarajan and Kumar, Raju Suresh and Rahaman, Mostafizur and Durairaju, Periyan and Alrehaili, Abdulaziz and Aldalbahi, Ali (2019) Glucosamine-6-phosphate synthase inhibiting C3-beta-cholesterol tethered spiro heterocyclic conjugates: Synthesis and their insight of DFT and docking study. In: BIOORGANIC CHEMISTRY, 88 .

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Official URL: https://dx.doi.org/10.1016/j.bioorg.2019.102920

Abstract

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-beta-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.

Item Type: Journal Article
Additional Information: copyright for this article belongs to ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords: Spiro steroid hybrids; 1XFF enzyme; Cycloaddition; DFT; HOMO-LUMO; Molecular docking
Department/Centre: Division of Biological Sciences > Biochemistry
Depositing User: Id for Latest eprints
Date Deposited: 05 Aug 2019 06:08
Last Modified: 05 Aug 2019 06:08
URI: http://eprints.iisc.ac.in/id/eprint/63382

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