13.

Synthesis and Antibacterial Evaluation of Novel Hydrophilic Ocotillol-Type Triterpenoid Derivatives from 20(S)- Protopanaxadiol

Yi Bi, Cong Ma, Zhiwen Zhou, Tingting Zhang, Hengyuan Zhang, Xiaochen Zhang, Jing Lu, Qingguo Meng, Peter J. Lewis and Jinyi Xu

School of pharmacy, Yantai University, Yantai 264005, P . R . China

Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia

State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China, Pharmaceutical University, Nanjing 210009, P . R . China

Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Guangxi Normal University, Guilin 541004, China

Abstract: Triterpenoid saponins are involved in plant defense systems to inhibit bacterial invasion. A new series of hydrophilic ocotillol-type triterpenoid derivatives 5-26 have been synthesi z ed with antibacterial activity against Gram-positive bacteria, including a community associated methicillin-resistant Staphylococcus aureus (CA-MRSA; strain USA300). From this series, compounds 6 and 15 were found to be the most active, both with MIC values of 2 μg/mL against B. subtilis 168 and 8 μg/mL against S. aureus USA300, respectively. Furthermore, subsequent assays showed that compounds 6 and 15 displayed strong synergistic effects at sub-MIC levels against both S. aureus USA300 and B. subtilis 168 when combined with two commercial antibiotics, kanamycin and chloramphenicol. Preliminary structure-activity relationship studies were also performed.

Keywords: Ocotillol; triterpenoid; antibacterial activity; synergistic effect. © 2015 ACG Publications. All rights reserved.