Design, synthesis, and antimicrobial activities of new tanshinone IIA esters

Abstract

Sixteen new ester derivatives with various partition coefficient (ClogP) values of tanshinone IIA (TSIIA), a major lipophilic component of Salvia miltiorrhiza, were designed and synthesised, including six aliphatic esters (3a–e, 5a), one phosphate ester (4c) and nine aromatic esters (5b–j). Their antimicrobial activities against three Gram-positive bacteria strains, Staphylococcus aureus, Bacillus subtilis, and Bacillus amyloliquefaciens, and two Gram-negative bacteria strains, Pseudomonas aeruginosa and Escherichia coli, as well as two fungi species, Candida albicans and Saccharomyces cerevisiae, were evaluated in vitro by broth microdilution susceptibility tests. The results showed that keeping ClogP values in a certain range is necessary for their antimicrobial activities. For those compounds with ClogP values between 5 and 10, their MIC values showed positive correlations with ClogP values. In particular, compound 3e exhibited fourfold and twofold higher potency than the standard drug amphotericin B against fungi C. albicans and S. cerevisiae with MIC values of 1.95 and 7.81 μg/mL, respectively.

Graphical abstract

Keywords:

• Tanshinone IIA
• ester derivatives
• ClogP
• synthesis
• antimicrobial

Acknowledgements

We thank Ms. Jian-Yang Pan (Pharmaceutical Informatics Institute, Zhejiang University) for performing the NMR and Mass spectrometry.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by the National Natural Science Foundation of China [grant number 21372198], [grant number 81473103)]; Zhejiang Provincial Natural Science Foundation of China [grant number Y14B020033].