Design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives

Shengtao Xu; Dahong Li; Lingling Pei; Hong Yao; Chengqian Wang; Hao Cai; Hequan Yao; Xiaoming Wu; Jinyi Xu

doi:10.1016/j.bmcl.2014.04.119

Design, synthesis and antimycobacterial activity evaluation of natural oridonin derivatives

Bioorg Med Chem Lett. 2014 Jul 1;24(13):2811-4. doi: 10.1016/j.bmcl.2014.04.119. Epub 2014 May 9.

Authors

Shengtao Xu¹, Dahong Li², Lingling Pei¹, Hong Yao³, Chengqian Wang³, Hao Cai¹, Hequan Yao¹, Xiaoming Wu¹, Jinyi Xu⁴

Affiliations

¹ 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.
² 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.
³ State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
⁴ 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.

PMID: 24835198
DOI: 10.1016/j.bmcl.2014.04.119

Abstract

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.

Keywords: Antimycobacterial activity; Oridonin; Tuberculosis; trans-Cinnamic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Diterpenes, Kaurane / chemical synthesis
Diterpenes, Kaurane / chemistry*
Diterpenes, Kaurane / pharmacology*
Dose-Response Relationship, Drug
Drug Design*
Microbial Sensitivity Tests
Molecular Structure
Mycobacterium / drug effects*
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Diterpenes, Kaurane
oridonin