RESUMO
Multi-drug-resistant microbial pathogens are a serious global health problem. New compounds with antibacterial activity serve as good candidates for developing novel antibacterial drugs which is very urgent and important. In this work, based on the unique scaffold of indirubin, an active ingredient of traditional Chinese medicine formulation Danggui Luhui Wan, we synthesized 29 indirubin-3'-monoximes and preliminarily evaluated their antibacterial activities. The antibacterial activity results demonstrated that the synthesized indirubin-3'-monoximes 5a-5z and 5aa-5ad displayed good potency against S. aureus ATCC25923 (MIC = 0.4-25.6 µg mL-1). Among them, we found that the 5-F, 5-Cl and 7-CF3 substituted indirubin-3'-monoximes 5r, 5s and 5aa also showed better antibacterial efficiency for S. aureus (MICs up to 0.4 µg mL-1) than the prototype natural product indirubin (MIC = 32 µg mL-1). More importantly, indirubin-3'-monoxime 5aa has certain synergistic effect with levofloxacin against clinic multidrug-resistant S. aureus (fractional inhibitory concentration index: 0.375). In addition, relevant experiments including electron microscopy observations, PI staining and the leakage of extracellular potassium ions and nucleic acid (260 nm) have been performed after treating S. aureus with indirubin-3'-monoxime 5aa, and the results revealed that indirubin-3'-monoximes could increase the cell membrane permeability of S. aureus. Although indirubin-3'-monoxime 5aa showed some cytotoxicity toward SH-SY5Y cells relative to compounds 5r and 5s, the skin irritation test of male mice after shaving showed that compound 5aa at a concentration of 12.8 µg mL-1 had no toxicity to mouse skin, and it could be used as a leading compound for skin antibacterial drugs.
RESUMO
OBJECTIVE: To evaluate the cost-effectiveness of comprehensive control strategy which mainly controls the schistosomiasis infection source in Lushan County from 2007 to 2012. METHODS: The data of the schistosomiasis endemic, Oncomelania hupensis snail status, control technology, and funding were collected and analyzed statistically in the endemic villages of Lushan County from 2007 to 2012. RESULTS: The schistosome infection rate of the residents decreased from 0.04% in 2007 to 0 in 2012. The numbers of advanced schistosomiasis patients decreased from 128 in 2007 to 121 in 2012. No acute schistosomiasis patients were found. The average density of living snails decreased from 0.06 snial/0.1 m2 to 0.05 snail/0.1 m2, with the decreased rate of 16.67%, and no schistosome infected snails were found. However, the snail area increased from 15.84 hm2 in 2007 to 52.12 hm2 in 2012, with the rise rate of 229.04%. The year per capita was 200.48 yuan, the cost of the infection rate decreasing by 1% was 949,900 yuan, and the cost of living snail density decreasing by 1% was 5,698,200 yuan. CONCLUSION: The cost-effectiveness of comprehensive control strategy which mainly controls the schistosomiasis infection source is relatively good in Lushan County from 2007 to 2012.
