The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: Modifications at C-12

Ming-Liang Liu; Xue-Ying Pan; Teng Yang; Wen-Ming Zhang; Tian-Qi Wang; He-Yun Wang; Hai-Xia Lin; Cai-Guang Yang; Yong-Mei Cui

doi:10.1016/j.bmcl.2016.10.018

The synthesis and antistaphylococcal activity of dehydroabietic acid derivatives: Modifications at C-12

Bioorg Med Chem Lett. 2016 Nov 15;26(22):5492-5496. doi: 10.1016/j.bmcl.2016.10.018. Epub 2016 Oct 12.

Authors

Ming-Liang Liu¹, Xue-Ying Pan², Teng Yang³, Wen-Ming Zhang¹, Tian-Qi Wang¹, He-Yun Wang¹, Hai-Xia Lin¹, Cai-Guang Yang⁴, Yong-Mei Cui⁵

Affiliations

¹ Department of Chemistry, Innovative Drug Research Center, College of Sciences, Shanghai University, Shanghai 200444, China.
² Nano Science and Technology Institute, University of Science and Technology of China, Suzhou 215123, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
³ Center for Research and Development of Fine Chemicals, Guizhou University, Guiyang 550025, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: yangcg@simm.ac.cn.
⁵ Department of Chemistry, Innovative Drug Research Center, College of Sciences, Shanghai University, Shanghai 200444, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: ymcui@t.shu.edu.cn.

PMID: 27777007
DOI: 10.1016/j.bmcl.2016.10.018

Abstract

A series of 12-oxime and O-oxime ether derivatives of dehydroabietic acid were synthesized and investigated for the antibacterial activity against Staphylococcus aureus Newman strain and five multidrug-resistant strains (NRS-1, NRS-70, NRS-100, NRS-108, and NRS-271). The aromatic oximate derivative 11a showed the highest activity with MIC of 0.39-0.78μg/mL against S. aureus Newman. Of note, compounds 10b, 11 and 14 showed the most potent antibacterial activity against five multidrug-resistant S. aureus with MIC values of 1.25-3.13μg/mL. These results offered useful information for further strategic optimization in search of the antibacterial candidates against infection of multidrug-resistant Gram-positive bacteria.

Keywords: Antistaphylococcal; Dehydroabietic acid; Multidrug-resistant; Oxime; Synthesis.

MeSH terms

Abietanes / chemical synthesis
Abietanes / chemistry*
Abietanes / pharmacology*
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacology*
Drug Resistance, Multiple, Bacterial
Humans
Microbial Sensitivity Tests
Oximes / chemical synthesis
Oximes / chemistry*
Oximes / pharmacology*
Staphylococcal Infections / drug therapy
Staphylococcus aureus / drug effects*
Structure-Activity Relationship

Substances

Abietanes
Anti-Bacterial Agents
Oximes
dehydroabietic acid