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Synthesis 2023; 55(24): 4145-4162
DOI: 10.1055/a-2161-0283
paper

Stereoselective Synthesis of Highly Functionalized Aminobenzothiazole-Fused Spirooxindole Derivatives: in silico and in vitro Anti-Diabetic Studies

Narayanasamy Nivetha
a   Organic and Polymer Synthesis Laboratory, Department of Chemistry, National Institute of Technology, Tiruchirappalli – 620 015, India
,
Shashank M. Patil
b   Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru – 570 015, India
,
Ramith Ramu
b   Department of Biotechnology and Bioinformatics, JSS Academy of Higher Education and Research, Mysuru – 570 015, India
,
Swamy Sreenivasa
c   Department of Chemistry, University College of Science, Tumkur University, Tumkur – 572 103, Karnataka, India
,
Sivan Velmathi  ∗
a   Organic and Polymer Synthesis Laboratory, Department of Chemistry, National Institute of Technology, Tiruchirappalli – 620 015, India
› Author AffiliationsThe authors SV and NN would like to thank DST-FIST-SR/FST/CS-II/2018/64 for funding the NMR Auto Sampler and HR-MS instrument facilities.
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Abstract

A series of highly functionalized spirooxindole pyrro­lizidine/pyrrolothiazole derivatives have been synthesized by the three-component 1,3-dipolar cycloaddition reaction of benzothiazolyl amides with isatin-based azomethine ylides. The pharmacologically significant spirooxindole derivatives bearing one quaternary carbon and four stereocenters were obtained in excellent yields (up to 93%). The compounds were screened for their anti-diabetic activity against two enzymes, α-glucosidase and α-amylase. The results exhibited potent inhibitory activity against these enzymes, especially N-(benzo[d]thiazol-2-yl)-5-fluoro-2-oxo-7′-phenyl-1′,6′,7′,7a′-tetrahydro-3′H-spiro[indoline-3,5′-pyrrolo[1,2-c]thiazole]-6′-carboxamide (6b), which showed excellent activity compared to the standard acarbose. Molecular docking against the receptors showed excellent interactions of the synthesized compounds in a similar way to acarbose. Further, the docking results of the spirooxindole pyrrolothiazole (6b) evinced the strong binding interactions of the compound with the receptors. Additionally, molecular dynamics simulations were carried out and confirmed the stability of the spirooxindole pyrrolothiazole (6b) in the active pockets of enzymes over 100 ns.

Key words

2-aminobenzothaizole - 1,3-dipolar cycloaddition - spirooxindole - anti-diabetes

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2161-0283.
  • Supporting Information


Publication History

Received: 04 July 2023

Accepted after revision: 28 August 2023

Accepted Manuscript online:
28 August 2023

Article published online:
04 October 2023

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