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

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 IC 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 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 , MRSA, , and . 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.