Design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives.
In an effort to develop novel potent antitubercular drugs, thirty-one oridonin derivatives were designed and prepared. All the compounds obtained were screened for their in vitro activities against Mycobacterium phlei, Mycobacterium smegmatis and Mycobacterium marinum. Among them, thirteen compounds showed significant inhibitory activity against M. phlei with MICs less than 2 μg/mL. Compounds 2k, 8d, 10c, 10d containing trans-cinnamic acid moiety were the most potent (MIC=0.5 μg/mL), comparable to the well-known antitubercular drug streptomycin. The preliminary structure-activity relationships (SARs) were also analyzed.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Shengtao
S
Xu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education and School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, 103 Wen Hua Road, Shenyang 110016, China.
Dahong
D
Li
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Lingling
L
Pei
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Hong
H
Yao
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Chengqian
C
Wang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Hao
H
Cai
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Hequan
H
Yao
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Xiaoming
X
Wu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China; Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China. Electronic address: jinyixu@china.com.
Jinyi
J
Xu
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009161:Mycobacterium / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D045786:Diterpenes, Kaurane; C011959:oridonin
Antimycobacterial activity; Oridonin; Tuberculosis; trans-Cinnamic acid