Design, Synthesis and Antibacterial Evaluation of 3-Substituted Ocotillol-Type Derivatives

• Published in: Molecules (Basel, Switzerland) Switzerland), 2018-12, Vol.23 (12), p.3320
• Main Authors: Wang, Kai-Yi, Zhou, Zhi-Wen, Zhang, Heng-Yuan, Cao, Yu-Cheng, Xu, Jin-Yi, Ma, Cong, Meng, Qing-Guo, Bi, Yi
• Format: Article
• Language: English
• Subjects: Antibacterial activity; Antibiotic resistance; Antibiotics; Bacteria; Drug resistance; E coli; Gram-negative bacteria; Gram-positive bacteria; Health risks; Metabolism; Minimum inhibitory concentration; Natural products; ocotillol; Pharmacophores; Public health; Saponins; Staphylococcus infections; structure-activity relationship; Structure-activity relationships; Substitutes; synthesis; triterpenoid saponin
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23123320

Antibiotic resistance has become a serious global problem that threatens public health. In our previous work, we found that ocotillol-type triterpenoid saponin showed good antibacterial activity. Based on preliminary structure-activity relationship, novel serious C-3 substituted ocotillol-type derivatives ⁻ were designed and synthesized. The in vitro antibacterial activity was tested on five bacterial strains ( 168, RN4220, DH5α, ATCC19606 and MRSA USA300) and compared with the tests on contrast. Among these derivatives, C-3 position free hydroxyl substituted compounds ⁻ , showed good antibacterial activity against Gram-positive bacteria. Furthermore, compound exhibited excellent antibacterial activity with minimum inhibitory concentrations (MIC) values of 2 μg/mL against MRSA USA300 and 4 μg/mL against . The structure-activity relationships of all current ocotillol-type derivatives our team synthesised were summarized. In addition, the prediction of absorption, distribution, metabolism, and excretion (ADME) properties and the study of pharmacophores were also conducted. These results can provide a guide to further design and synthesis works.