The Toxicity And Pharmacodynamics Study Of Chemical Compounds Pleuromutilin-sulfonamides

With the rapid development of China's animal husbandry and aquaculture, animal diseases, especially infectious diseases is increasing. Antibiotics as the primary means of prevention and treatment of aquaculture infectious diseases, using the amount has increased, resulting in the growing phenomenon of bacterial resistance, particularly methicillin-resistant Staphylococcus aureus(MRSA), penicillin-resistant Streptococcus pneumonia(PRSP), multidrug-resistant Pseudomonas aeruginosa(MDRPA) and vancomycin-resistant enterococci(VRE) and other resistant bacteria appear. The bacterial resistance posed a serious threat to human health, study effective new antibiotic is imminent.Currently, the use of the principles of synthesis of new compounds split method by many research institutions and pharmaceutical companies alike. Pleuromutilins antibacterial antibiotics with unique mechanisms rarely conventional antibiotics cross-resistance, which is a known antibiotic or pharmacophore put together, are expected to screen out effective new drug-resistant compound. To this end, our group split reference drugs principle, design synthesized 46 new pleuromutilins- sulfa split was screened out of six have good antimicrobial activity.In this paper, we choose one representative split was(A1, A3), to determine their in vivo efficacy and toxicity, the class was split to provide evidence for the role of law set forth in the animals. Toxicity Test Reference GB GB 15193.3-2003 principles and methods, the results show that the split was A1, A3 on mice acute oral toxicity LD50 of 1694 mg / kg, 1356.7mg / kg, according to toxicity grading belong to the low toxicity substance, the toxicity or quite low compared to the control drug valnemulin(LD50 = 1374.4 mg / kg). Thigh and abdomen of mice by subcutaneous injection of Staphylococcus aureus ATCC29213, create two infection models. In valnemulin to control drugs, oral administration, research was split A1 therapeutic effect of the two disease models. The results showed that the split was A1 high, medium and low(507 mg/kg ?338 mg/kg?169mg/kg)dose group of the number of viable cells in vivo in mice infected with Staphylococcus thigh after 24 h is:(7.01 ± 0.32) × 106 CFU / g,(2.32 ± 0.12) × 107 CFU / g,(9.9 ± 0.43) × 107 CFU / g, compared with the control group, the difference was significant(P <0.01), with valnemulin fairly. A1 high school low dose of subcutaneous infection suppurative disease cure rate was 88.89%, 77.78% and 50%, respectively, before and after administration of purulent area average reduction 2.08 cm2,1.59 cm2,1.42 cm2. Valnemulin high school low-dose group were reduced by an average of purulent 1.42 cm2,0.69 cm2,0.49 cm2 area before and after the administration, while the control group fester area increased by an average 0.36 cm2. The results show that A1 good for subcutaneous suppurative disease treatment, has good prospects for application development, and laid a foundation for further study of these compounds.