2. Academic Validation
  3. Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents

Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents

  • Bioorg Med Chem Lett. 2024 Aug 1:108:129789. doi: 10.1016/j.bmcl.2024.129789.
Kripa Shanker Nainawat 1,  Kratika Gupta 1,  Neelam Gupta 2,  Romila Singh 3,  Divya Mishra 3,  Abhishek Nirwan 2,  Meenakshi Verma 4,  Amrita Singh 4,  Prema G Vasudev 4,  Feroz Khan 5,  Durga Prasad Mishra 2,  Atul Gupta 6
Affiliations

Affiliations

  • 1 Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
  • 2 Division of Endocrinology, CSIR-Central Drug Research Institute, Sec-10, Jankipuram Extension, Lucknow 226024, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
  • 3 Division of Endocrinology, CSIR-Central Drug Research Institute, Sec-10, Jankipuram Extension, Lucknow 226024, India.
  • 4 Plant Biotechnology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
  • 5 Technology Dissemination and Computational Biology Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India.
  • 6 Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Kukrail Road, Lucknow 226015, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh 201002, India. Electronic address: [email protected].
PMID: 38729318 DOI: 10.1016/j.bmcl.2024.129789
Abstract

Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast Cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and Apoptosis of ER+ and ER- Cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering Apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -β.

Keywords

2,2-Dimethyl-chroman; Anticancer; Benzopyran; Estrogen; Tamoxifen.

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