两种AZT-氟喹诺酮偶联物体外抗HIV-1及抗菌活性的研究  

The anti-HIV-1 and antibacterial activities of two novel AZT-fuoroquinolones conjugates

作　　者：龙晶[1,3] Dharmarajan Sriram 张高红[1] 郑永唐[1] 

机构地区：[1]中国科学院昆明动物研究所动物模型和人类疾病机理重点实验室、分子免疫药理学实验室,云南昆明650223 [2]Birla Institute of Technology ＆ Science, Pilani 333031, India [3]中国科学院研究生院,北京100039

出　　处：《中国药理学通报》2009年第1期30-34,共5页Chinese Pharmacological Bulletin

基　　金：国家科技攻关计划资助项目(No2004BA719A14);中国科学院知识创新工程重要方向资助项目(NoKSCX1-YW-R-24);云南省科技攻关计划资助课题(No2004NG12)

摘　　要：目的体外测定两种AZT-氟喹诺酮偶联物SRLZ和SROZ的抗HIV-1活性及抗菌活性。方法通过合胞体抑制、HIV-1感染细胞保护、HIV-1 p24抗原测定等方法检测急性感染中化合物对HIV-1实验株、临床分离株的抑制作用和对慢性感染细胞中的病毒复制影响;通过体外金黄色葡萄球菌的抑制实验检测化合物的抗菌活性。结果AZT-氟喹诺酮偶联物SRLZ和SROZ能抑制HIV-1实验株诱导的合胞体形成,减少病毒感染细胞的死亡和抑制病毒在细胞内的复制;SRLZ和SROZ对HIV-1临床分离株也有较好的抑制作用;SRLZ和SROZ对HIV-1的抑制活性与AZT相近;AZT-氟喹诺酮偶联物也能抑制金黄色葡萄球菌,其MIC值与其相应的阳性药物相近。结论SRLZ和SROZ有很好的抗HIV-1活性和抗菌活性。Aim To study the anti-HIV-1 and antibac- terial activities of two novel AZT-fuoroquinolones conjugates, SRLZ and SROZ. Methods The inhibition of syncytia formation induced by HIV - 1 was determined under microscopy, protection of HIV-1 induced MT-4 cell lytic effects was measured by MTT assay, level of HIV-1 p24 antigen in acute and chronic HIV-1 infection were assayed by ELISA; ELISA reader was detected through the concentration of Staphylococcus aureus. Results AZT-fuoroquinolones conjugates SRLZ and SROZ markedly inhibited syncytium formation and protected HIV-1 induced MT-4 cell lytic effects and also showed obviously inhibitory effect on the HIV-1 clinical isolate. The anti-HIV-1 activities of the AZT-fuoroquinolones conjugates were similar to the AZT; SRLZ and SROZ also showed significant inhibition effect on the Staphylococcus aureus, the MICs were similar to their corresponding positive drugs, lomefloxacin hydro- chloride and ofloxacin. Conclusion The novel AZT- fuoroquinolones conjugates SRLZ and SROZ are potent anti-HIV-1 and antibacterial agents.

关 键 词：AZT氟-喹诺酮偶联物 HIV-1 金黄色葡萄球菌 抗HIV-1 抗菌 

分 类 号：R373.9[医药卫生—病原生物学] R378.11[医药卫生—基础医学]