Amoroso Rosa, De Lellis Laura, Florio Rosalba, Moreno Nazaret, Agamennone Mariangela, De Filippis Barbara, Giampietro Letizia, Maccallini Cristina, Fernández Inmaculada, Recio Rocío, Cama Alessandro, Fantacuzzi Marialuigia, Ammazzalorso Alessandra
Department of Pharmacy, "G. d'Annunzio" University of Chieti-Pescara, Via Dei Vestini 31, 66100 Chieti, Italy.
Center for Advanced Studies and Technology CAST, Via Luigi Polacchi 11, 66100 Chieti, Italy.
Pharmaceuticals (Basel). 2022 Jul 28;15(8):937. doi: 10.3390/ph15080937.
The antiproliferative effects played by benzothiazoles in different cancers have aroused the interest for these molecules as promising antitumor agents. In this work, a library of phenylacetamide derivatives containing the benzothiazole nucleus was synthesized and compounds were tested for their antiproliferative activity in paraganglioma and pancreatic cancer cell lines. The novel synthesized compounds induced a marked viability reduction at low micromolar concentrations both in paraganglioma and pancreatic cancer cells. Derivative showed a greater antiproliferative effect and higher selectivity index against cancer cells, as compared to other compounds. Notably, combinations of derivative with gemcitabine at low concentrations induced enhanced and synergistic effects on pancreatic cancer cell viability, thus supporting the relevance of compound in the perspective of clinical translation. A target prediction analysis was also carried out on by using multiple computational tools, identifying cannabinoid receptors and sentrin-specific proteases as putative targets contributing to the observed antiproliferative activity.
苯并噻唑在不同癌症中发挥的抗增殖作用引发了人们对这些分子作为有前景的抗肿瘤药物的兴趣。在这项工作中，合成了一个含有苯并噻唑核的苯乙酰胺衍生物库，并测试了这些化合物在副神经节瘤和胰腺癌细胞系中的抗增殖活性。新合成的化合物在低微摩尔浓度下对副神经节瘤和胰腺癌细胞均诱导了显著的活力降低。与其他化合物相比，衍生物 表现出更大的抗增殖作用和对癌细胞更高的选择性指数。值得注意的是，衍生物 与吉西他滨的低浓度组合对胰腺癌细胞活力诱导了增强的协同作用，从而支持了化合物 在临床转化方面的相关性。还通过使用多种计算工具对 进行了靶点预测分析，确定大麻素受体和类泛素特异性蛋白酶为可能导致观察到的抗增殖活性的靶点。
