2. Academic Validation
  3. Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads

Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads

  • Molecules. 2017 Apr 7;22(4):590. doi: 10.3390/molecules22040590.
Yi Bi 1,  Xian-Xuan Liu 2,  Heng-Yuan Zhang 3,  Xiao Yang 4,  Ze-Yun Liu 5,  Jing Lu 6,  Peter John Lewis 7,  Chong-Zhi Wang 8 9,  Jin-Yi Xu 10,  Qing-Guo Meng 11,  Cong Ma 12,  Chun-Su Yuan 13 14
Affiliations

Affiliations

  • 1 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. beeyee_413@163.com.
  • 2 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. opendekevin@163.com.
  • 3 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. panacea0928@163.com.
  • 4 Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. xiaoyang@cuhk.edu.hk.
  • 5 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. 18766565610@163.com.
  • 6 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. tainche@126.com.
  • 7 Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. peter.lewis@newcastle.edu.au.
  • 8 Tang Center for Herbal Medicine Research, the University of Chicago, Chicago, IL 60637, USA. czwang@dacc.uchicago.edu.
  • 9 Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA. czwang@dacc.uchicago.edu.
  • 10 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. jinyixu@china.com.
  • 11 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. qinggmeng@163.com.
  • 12 Department of Applied Biology and Chemical Technology, and State Key Laboratory of Chirosciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China. cong.ma@polyu.edu.hk.
  • 13 Tang Center for Herbal Medicine Research, the University of Chicago, Chicago, IL 60637, USA. cyuan@dacc.uchicago.edu.
  • 14 Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA. cyuan@dacc.uchicago.edu.
PMID: 28387737 DOI: 10.3390/molecules22040590
Abstract

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(S)-protopanaxadiol were synthesized and evaluated for their Antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum 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 5c and 6c enhanced the susceptibility of B. subtilis 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.

Keywords

antibacterial activity; derivatives; ocotillol; synergistic effect; synthesis.

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