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.
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.
Bioorg Med Chem Lett. 2024 Aug 1;108:129789. doi: 10.1016/j.bmcl.2024.129789. Epub 2024 May 8.
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 IC 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.
受体是蛋白质大分子，在正常/无配体条件下处于 apo 形式。当配体接近时，受体的 apo 形式会根据配体的立体化学发生特定的立体化学变化。因此，合成了一系列取代的二甲基色满基立体化学柔性和约束性他莫昔芬类似物作为抗乳腺癌药物。合成的化合物 19a-e、20a-e、21 和 22a-e 在 IC 值为 8.5-25.0 µM 范围内对雌激素受体阳性（ER，MCF-7）和阴性（ER，MDA MB-231）细胞表现出显著的增殖抑制活性。在所有这些化合物中，评估了四个潜在的分子，即 19b、19e、22a 和 22c，以研究它们对 ER 和 ER 癌细胞（MCF-7 和 MDA MB-231 细胞）细胞分裂周期和细胞凋亡的影响，结果表明这些化合物通过触发细胞凋亡具有抗增殖活性。计算机对接实验阐明了化合物与雌激素受体-α和-β 的可能亲和力。
