Synthesis, anticancer and antibacterial evaluation of novel spiramycin-acylated derivatives†

IF 3.9 3区 化学 Q2 CHEMISTRY, MULTIDISCIPLINARY
RSC Advances Pub Date : 2024-12-09 DOI:10.1039/D4RA03126A
Zhiwei Wang, Junxiang Cheng, Hui Wen, Tao Hou, Fengbin Luo, Yaodong Wang, Xingjun Xu, Yanfang Liu, Yaopeng Zhao and Xinmiao Liang
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Abstract

Spiramycin and its derivatives are commonly used antimicrobials, and its derivative, carrimycin, has recently been found to have good anticancer potential. Here, we found that the 4′′-OH of spiramycin can be selectively acylated, resulting in a series of novel spiramycin derivatives with a structure similar to carrimycin. Anticancer studies showed that most of the derivatives exhibited moderate to good anti-proliferative activity against four cancer cell lines, including HGC-27, HT-29, HCT-116 and HeLa, especially compound 14, which has the strongest activity against HGC-27 cells with an IC50 value of 0.19 ± 0.02 μM. Pharmacological studies on HGC-27 cells revealed that compound 14 could arrest the cell cycle in the S phase, raise ROS levels, and induce cell apoptosis via activation of Erk/p38 MAPK signaling pathways. In addition, antibacterial studies showed that most of the spiramycin I derivatives modified at the 4′′-OH group enhanced antibacterial activity on the four tested strains, including S. aureus, S. aureus MRSA, S. epidermidis, and B. subtilis. In particular, compound 16 was the most effective one and comparable to linezolid, a commonly used first-line antimicrobial. These results suggest that spiramycin I derivatives may provide an opportunity to design new anticancer or antibacterial agents, even dual-function agents.

Abstract Image

新型螺旋霉素酰化衍生物的合成、抗癌及抗菌评价
螺旋霉素及其衍生物是常用的抗菌剂,其衍生物carrimycin最近被发现具有良好的抗癌潜力。在这里,我们发现螺旋霉素的4”-OH可以选择性地被酰化,从而产生一系列具有类似于carrimycin结构的新型螺旋霉素衍生物。抗癌研究表明,大部分衍生物对HGC-27、HT-29、HCT-116和HeLa等4种肿瘤细胞均有中等至良好的抗增殖活性,其中化合物14对HGC-27细胞的抗增殖活性最强,IC50值为0.19±0.02 μM。对HGC-27细胞的药理研究表明,化合物14可以通过激活Erk/p38 MAPK信号通路,使细胞周期停留在S期,提高ROS水平,诱导细胞凋亡。此外,抗菌研究表明,大部分经4”-OH基团修饰的螺旋霉素I衍生物对金黄色葡萄球菌、金黄色葡萄球菌MRSA、表皮葡萄球菌和枯草芽孢杆菌等4种被试菌株的抗菌活性均增强。特别是,化合物16是最有效的,可与常用的一线抗菌剂利奈唑胺相媲美。这些结果表明,螺旋霉素I衍生物可能为设计新的抗癌或抗菌药物,甚至是双功能药物提供了机会。
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来源期刊
RSC Advances
RSC Advances chemical sciences-
CiteScore
7.50
自引率
2.60%
发文量
3116
审稿时长
1.6 months
期刊介绍: An international, peer-reviewed journal covering all of the chemical sciences, including multidisciplinary and emerging areas. RSC Advances is a gold open access journal allowing researchers free access to research articles, and offering an affordable open access publishing option for authors around the world.
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