2. Academic Validation
  3. Palladium catalyzed migratory heck coupling of arteannuin B and boronic acids: An approach towards the synthesis of antiproliferative agents in breast and lung cancer cells

Palladium catalyzed migratory heck coupling of arteannuin B and boronic acids: An approach towards the synthesis of antiproliferative agents in breast and lung cancer cells

  • Bioorg Chem. 2022 May;122:105694. doi: 10.1016/j.bioorg.2022.105694.
Javeed Ur Rasool 1,  Khalid Bashir Mir 2,  Majeed Shaikh 3,  Aabid H Bhat 3,  Yedukondalu Nalli 1,  Anam Khalid 4,  Syed Mudabir Ahmad 2,  Anindya Goswami 5,  Asif Ali 6
Affiliations

Affiliations

  • 1 Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India; Natural Product and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 2 Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India; Pharmacology Division, CSIR-Indian Indian Institute of Integrative Medicine, Jammu 180001, India.
  • 3 Natural Product and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
  • 4 Department of Chemistry, SCLS, Jamia Hamdard, New Delhi 110062, India.
  • 5 Pharmacology Division, CSIR-Indian Indian Institute of Integrative Medicine, Jammu 180001, India.
  • 6 Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India; Natural Product and Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India. Electronic address: [email protected].
PMID: 35286922 DOI: 10.1016/j.bioorg.2022.105694
Abstract

We have recently highlighting the role of spiroisoxazoline arteannuin B derivatives in mediating proinflammatory cytokines like IL-6, TNfα and NO in vitro. In the present study, a series of new β-arylated arteannuin B analogues were synthesized through coupling with arylboroic acids and evaluated for their in vitro cytotoxic activity in a panel of six Cancer cell lines. The binding efficiency was verified by docking of the original ligand within the active site of ATPase domain of GRP78 (PDB ID: 3LDL) at a resolution of 2.30 Å with the score energy of -8.07 kcal/mol. Among the new compounds 3a, 3b, 3d, 3i, 3j and 3n displayed potent cytotoxic potential with an IC50 from 2 to 18 µM and compound 3i was proven to be the most potent cytotoxic and anti-proliferative compound of all the six distinct cell lines. Compound 3i exhibited promising Apoptosis inducing potential in breast Cancer cells and stalled their wound healing properties and was effective in blocking the migration of Cancer cells.

Keywords

Anti-proliferative; Apoptosis; Arteannuin B; Aryl boronic acids; Proinflammatory.

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