Bi Yi, Liu Xian-Xuan, Zhang Heng-Yuan, Yang Xiao, Liu Ze-Yun, Lu Jing, Lewis Peter John, Wang Chong-Zhi, Xu Jin-Yi, Meng Qing-Guo, Ma Cong, Yuan Chun-Su
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China.
State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Molecules. 2017 Apr 7;22(4):590. doi: 10.3390/molecules22040590.
Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20()-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria ( 168 and MRSA USA300) and Gram-negative bacteria ( PAO1 and ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2-16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives and enhanced the susceptibility of 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.
由于细菌对抗生素的耐药性迅速增加以及研发中的新型药物稀缺，细菌感染仍然是一个全球性问题。因此，迫切需要新型抗菌剂，其单独使用以及与传统抗生素联合使用均有效。本文合成了一系列从天然20（S）-原人参二醇修饰而来的抗菌奥科梯隆型C-24差向异构体，并对其抗菌活性进行了评估。根据体外对革兰氏阳性菌（168和MRSA USA300）和革兰氏阴性菌（PAO1和ATCC19606）的筛选结果，这些衍生物表现出良好的抗菌活性，尤其是对革兰氏阳性菌，其最低抑菌浓度（MIC）值为2-16μg/mL。随后的协同抗菌试验表明，衍生物和增强了168和MRSA USA300对氯霉素（CHL）和卡那霉素（KAN）的敏感性（FICI<0.5）。我们的数据表明，在C-3位带有长链氨基酸取代基的奥科梯隆型衍生物是对抗抗生素耐药病原体MRSA USA300的良好先导化合物，其可以提高KAN和CHL在低得多的浓度下表现出抗菌活性的能力，同时降低毒性。
