Microtubule-targeting agents (MTA) have enjoyed significant clinical success for decades. However, several mechanisms may cause inactivation of such drugs, leading to acquired resistance in patients treated with them. Therefore, drugs containing a stilbene-like skeleton and possessing dual inhibitory activity may provide a new and differentiated treatment for patients to overcome challenging acquired resistance. A new compound (16c) displays promising anticancer activity with GI50 of 22 ± 2 and 12 ± 0.1 nM in vincristine-resistant nasopharyngeal (KB-Vin) cancer cells and etoposide-resistant nasopharyngeal (KB-7D) cancer cells and is better than vincristine, etoposide, ABT-751, and MS-275. A mechanistic study revealed that 16c interferes with the cell cycle distribution and induces cell cycle arrest at the G2/M phase and severe mitotic spindle defects followed by apoptosis. In addition, it produces much more significant cytotoxicity than vincristine and etoposide in the corresponding resistant cells, indicating that it may be a promising candidate to overcome drug resistance in cancer cells. Compound 16c also displays inhibitory activity against HDAC 1 and HDAC 2 with IC50 values of 1.07 μM, and 1.47 μM, respectively. These findings may lead to a new type of structural motif for future development of drugs that could overcome acquired resistance to MTAs.

中文翻译：

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N-苯基-4-（2-苯基磺酰胺基）-苯甲酰胺类药物在抗药性癌细胞中作为微管靶向剂的设计，合成和评估，显示出HDAC抑制作用。

靶向微管的药物（MTA）在临床上已经取得了数十年的成功。但是，多种机制可能导致此类药物失活，从而导致接受该药物治疗的患者获得抵抗力。因此，含有二苯乙烯类骨架并且具有双重抑制活性的药物可能为患者克服挑战性的获得性耐药提供新的差异化治疗方法。一种新化合物（16c）在耐长春新碱的鼻咽（KB-Vin）癌细胞和依托泊苷抗性的鼻咽（KB-7D）癌细胞中显示出有希望的抗癌活性，GI50为22±2和12±0.1 nM。 ，依托泊苷，ABT-751和MS-275。一项机理研究表明，16c干扰细胞周期分布并诱导细胞周期停滞在G2 / M期，并导致严重的有丝分裂纺锤体缺陷，随后发生凋亡。此外，它在相应的耐药细胞中比长春新碱和依托泊苷产生的细胞毒性要大得多，这表明它可能是克服癌细胞耐药性的有前途的候选药物。化合物16c还显示出对HDAC 1和HDAC 2的抑制活性，IC50值分别为1.07μM和1.47μM。这些发现可能会为药物的未来开发带来一种新型的结构基序，从而可以克服对MTA的获得性耐药性。表明它可能是克服癌细胞耐药性的有前途的候选者。化合物16c还显示出对HDAC 1和HDAC 2的抑制活性，IC50值分别为1.07μM和1.47μM。这些发现可能会为药物的未来开发带来一种新型的结构基序，从而可以克服对MTA的获得性耐药性。表明它可能是克服癌细胞耐药性的有前途的候选者。化合物16c还显示出对HDAC 1和HDAC 2的抑制活性，IC50值分别为1.07μM和1.47μM。这些发现可能会为药物的未来开发带来一种新型的结构基序，从而可以克服对MTA的获得性耐药性。