尽管癌症研究和治疗取得了重大进展，但乳腺癌仍然是一个具有挑战性的医学问题，并且是生物医学研究的高度优先事项。目前的研究旨在确定一组基于咪唑-吡啶的支架对受体表达不同（雌激素受体（ER）、孕激素受体（PR）和 HER-2）的多种乳腺癌细胞系的抗癌活性。 。通过多组分和烷基化反应合成了一系列 10 个分子（编码 5a-5j）。 FTIR、MS、1H 和 13C NMR 光谱分析证实了合成分子的结构和纯度。随后，测试了这些分子抑制代表乳腺癌的细胞系（即 MDA-MB-468（ER-、PR- 和 HER-）、BT-474（ER、PR、和 HER ）、T-47D（ER 、 PR 和 HER-）和 MCF-7（ER 、PR 和 HER-）体外。在这 10 个分子中，5a、5c、5d 和 5e 表现出更好的效力，针对 BT-474 和 MDA-MB-468 细胞系处理 24 小时时的 IC50 < 50 μM 证明了这一点。然而，除了 5d 外，在 24h 对 T47D 和 MCF-7 细胞系进行测试时，IC50 值远高于 50 μM。延长处理 48 小时降低了这些分子的作用，观察到 IC50 增加。在小鼠中，腹腔注射 5e 可以延缓艾利希腹水癌 (EAC) 的生长，并且在测试剂量下不会引起任何器官毒性。总之，我们报告了一系列新的咪唑-吡啶分子的合成方案和关键结构要求，用于体外抑制乳腺癌细胞和体内抑制 EAC 肿瘤的可行性。© 2023 作者。由美国化学会出版。

Breast cancer remains a challenging medical issue and is a high priority for biomedical research despite significant advancements in cancer research and therapy. The current study aims to determine the anticancer activity of a group of imidazole-pyridine-based scaffolds against a variety of breast cancer cell lines differing in their receptor expression (estrogen receptor (ER), progesterone receptor (PR), and HER-2). A series of 10 molecules (coded 5a-5j) were synthesized through multicomponent and alkylation reactions. FTIR, MS, 1H, and 13C NMR spectral analyses confirmed the structures and purity of the synthesized molecules. Subsequently, these molecules were tested for their ability to inhibit the viability of cell lines representing carcinoma of the breast, viz., MDA-MB-468 (ER-, PR-, and HER-), BT-474 (ER+, PR+, and HER+), T-47D (ER+, PR+, and HER-), and MCF-7 (ER+, PR+, and HER-) in vitro. Among these 10 molecules, 5a, 5c, 5d, and 5e exhibited better potency, as evidenced by IC50 < 50 μM at 24 h of treatment against BT-474 and MDA-MB-468 cell lines. However, except for 5d, the IC50 value is much higher than 50 μM when tested against T47D and MCF-7 cell lines at 24h. Extended treatment for 48 h reduced the effect of these molecules, as an increase in IC50 was observed. In mice, intraperitoneal administration of 5e retarded the Ehrlich ascites carcinoma (EAC) growth without causing any organ toxicity at the doses tested. In summary, we report the synthesis scheme and key structural requirements for a new series of imidazole-pyridine molecules for in vitro inhibition of the feasibility of breast cancer cells and in vivo inhibition of EAC tumors.© 2023 The Authors. Published by American Chemical Society.