Life and Health Sciences Research Institute (ICVS), University of Minho, Campus of Gualtar, Braga, Portugal; ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Department of Chemistry, University of Minho, Campus of Gualtar, Braga, Portugal.
Bioorg Chem. 2020 Jul;100:103942. doi: 10.1016/j.bioorg.2020.103942. Epub 2020 May 17.
A selection of new chromeno[2,3-b]pyridines was prepared from chromenylacrylonitriles and N-substituted piperazines, using a novel and efficient synthetic procedure. The compounds were tested for their anticancer activity using breast cancer cell lines MCF-7, Hs578t and MDA-MB-231 and the non-neoplastic cell line MCF-10A for toxicity evaluation. In general, compounds showed higher activity towards the luminal breast cancer subtype (MCF-7), competitive with the reference compound Doxorubicin. The in vivo toxicity assay using C. elegans demonstrated a safe profile for the most active compounds. Chromene 3f revealed a promising drug profile, inhibiting cell growth and proliferation, inducing cell cycle arrest in G/M phase, apoptosis and microtubule destabilization. The new compounds presented exciting bioactive features and may be used as lead compounds in cancer related drug discovery.
从色烯基丙烯腈和 N-取代哌嗪中选择了一系列新的色烯并[2,3-b]吡啶，采用了新颖有效的合成方法。使用乳腺癌细胞系 MCF-7、Hs578t 和 MDA-MB-231 以及非肿瘤细胞系 MCF-10A 对化合物进行了抗癌活性测试，以评估其毒性。总的来说，化合物对腔型乳腺癌亚型（MCF-7）表现出更高的活性，与参考化合物阿霉素相当。使用秀丽隐杆线虫进行的体内毒性试验表明，最活跃的化合物具有安全的特性。色烯 3f 显示出有希望的药物特性，能抑制细胞生长和增殖，诱导 G/M 期细胞周期停滞、细胞凋亡和微管去稳定化。这些新化合物具有令人兴奋的生物活性特征，可作为癌症相关药物发现的先导化合物。
