title: Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads.
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. subtilis168 and MRSA USA300) and Gram-negative bacteria (P. aerPAO1 andA. baumATCC19606) 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 derivatives5cand6cenhanced the susceptibility ofB. subtilis168 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.
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Bi
authors.affiliation: 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.
authors.forename: Xian-Xuan
authors.initials: XX
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. panacea0928@163.com.
authors.forename: Heng-Yuan
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong, China. xiaoyang@cuhk.edu.hk.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Ze-Yun
authors.initials: ZY
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Lu
authors.affiliation: Biological Sciences, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia. peter.lewis@newcastle.edu.au.
authors.forename: Peter John
authors.initials: PJ
authors.lastname: Lewis
authors.affiliation: Tang Center for Herbal Medicine Research, the University of Chicago, Chicago, IL 60637, USA. czwang@dacc.uchicago.edu.|Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA. czwang@dacc.uchicago.edu.
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China. jinyixu@china.com.
authors.forename: Jin-Yi
authors.initials: JY
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Cong
authors.initials: C
authors.lastname: Ma
authors.affiliation: Tang Center for Herbal Medicine Research, the University of Chicago, Chicago, IL 60637, USA. cyuan@dacc.uchicago.edu.|Department of Anesthesia and Critical Care, The University of Chicago, Chicago, IL 60637, USA. cyuan@dacc.uchicago.edu.
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004357:Drug Synergism; D036145:Ginsenosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D036145:Ginsenosides; C524540:ocotillol
keywords: antibacterial activity; derivatives; ocotillol; synergistic effect; synthesis