Enhancement of water solubility and anti-tuberculosis activities by a novel artemisinin derivative
10.16438/j.0513-4870.2018-0876
- VernacularTitle:新型青蒿素衍生物改善溶解度及其抗结核活性研究
- Author:
Ning ZHANG
1
;
Yang LIU
2
;
Ye LI
2
;
Ping HU
3
Author Information
1. School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China
2. Shanxi Chinese Medicine Research Institute, Xi'an 710003, China
3. School of Pharmaceutical Sciences, Chongqing University, Chongqing 401331, China; Shanxi Chinese Medicine Research Institute, Xi'an 710003, China
- Publication Type:Research Article
- Keywords:
artemisinin;
erivative;
tuberculosis;
arginine;
solubility
- From:
Acta Pharmaceutica Sinica
2019;54(1):36-40
- CountryChina
- Language:Chinese
-
Abstract:
Artemisinin and its derivatives have been proved for their anti-tuberculosis activities, despite its low water solubility which hampered its efficacy and corresponding formulation development. In this study we designed and synthesized a novel artemisinin analog by conjugating an arginine through a succinic acid linker. This design not only enhanced the water solubility of the artemisinin, but also increased the efficacy of the molecule towards tuberculosis bacteria due to disruption by arginine. The results showed that the solubility of the synthesized derivatives A-2 and A-3 increased 19.8-27.8 folds compared to artemisinin. In vitro cytotoxicity experiment showed that compound A-3 had negligible toxicity to THP-1 cells up to 1 mg·mL-1, the minimal inhibitory concentration (MIC) of A-2 and A-3 was 20 and 10 μg·mL-1, respectively, which was 5 or 10 times lower than that of artemisinin. Intracellular bacteria inhibition experiment showed that compound A-3 at lower concentrations such as 100 or 200 μg·mL-1 significantly inhibited the growth of tuberculosis bacteria (P<0.05 or P<0.01), which efficacy was stronger than artemisinin at the concentration of 100 μg·mL-1. These results strongly suggested that compound A-3 was a potential anti-tuberculosis lead compound.
