2. Academic Validation
  3. Synthesis and biological studies of new piperidino-1,2,3-triazole hybrids with 3-aryl isoxazole side chains

Synthesis and biological studies of new piperidino-1,2,3-triazole hybrids with 3-aryl isoxazole side chains

  • Bioorg Med Chem Lett. 2021 Nov 15:52:128390. doi: 10.1016/j.bmcl.2021.128390.
Appala Venkata Ramana Murthy 1,  Vennu Narendar 2,  Nangunoori Sampath Kumar 2,  Pasula Aparna 3,  Anagani Kanaka Durga Bhavani 4,  Hélène Solhi 5,  Rémy Le Guevel 5,  Julie Roul 6,  Fabien Gautier 6,  Philippe Juin 7,  Chada Raji Reddy 8,  Paul Mosset 9,  Nicolas Levoin 10,  René Grée 9
Affiliations

Affiliations

  • 1 Chemveda Life Sciences India Pvt. Ltd., #B-11/1, IDA Uppal, Hyderabad-500039, Telangana, India; Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, Telangana, India.
  • 2 Chemveda Life Sciences India Pvt. Ltd., #B-11/1, IDA Uppal, Hyderabad-500039, Telangana, India.
  • 3 Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, Telangana, India.
  • 4 Osmania University, Department of Chemistry, Hyderabad 500007, Telangana, India.
  • 5 Univ Rennes, Plateform ImPACcell, BIOSIT, F-35000 Rennes, France.
  • 6 UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 "Cell Survival and Tumor Escape in Breast Cancer", Institut de Recherche Thérapeutique de l'Université de Nantes, 8 Quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France; Institut de Cancérologie de l'Ouest, Centre de Lutte contre le Cancer René Gauducheau, Boulevard Jacques Monod, 44805 Saint Herblain-Nantes Cedex, France.
  • 7 UMR 892 INSERM/6299 CNRS/Université de Nantes, Team 8 "Cell Survival and Tumor Escape in Breast Cancer", Institut de Recherche Thérapeutique de l'Université de Nantes, 8 Quai Moncousu, BP 70721, 44007 Nantes Cedex 1, France.
  • 8 Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 9 Univ Rennes, CNRS, ISCR (Institut des Sciences Chimiques de Rennes), UMR 6226, F-35000 Rennes, France.
  • 10 Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint Grégoire, France.
PMID: 34601029 DOI: 10.1016/j.bmcl.2021.128390
Abstract

A small library of new piperidine-triazole hybrids with 3-aryl isoxazole side chains has been designed and synthesized. Their cytotoxicity against a panel of seven Cancer cell lines has been established. For the most promising compound, an IC50 value of 3.8 μM on PUMA/Bcl-xL interaction in live Cancer cells was established through BRET analysis. A rationale was proposed for these results through complete molecular modelling studies.

Keywords

BRET (Bioluminescence Resonance Energy Transfer); Bcl-xL (B-cell lymphoma-extra large); Cancer; Molecular modelling; PUMA (p53 upregulated modulator of apoptosis); Protein-protein interactions.

Figures