Dinakaran Murugesan, Senthilkumar Palaniappan, Yogeeswari Perumal, Sriram Dharmarajan
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani, Rajasthan, India.
Biomed Pharmacother. 2009 Jan;63(1):11-8. doi: 10.1016/j.biopha.2007.10.009. Epub 2007 Nov 20.
Sixteen novel 3-nitro-2-(sub)-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8-naphthyridine-6-carboxylic acids were synthesized from 2,6-dimethoxynicotinic acid and 2-aminothiophenol and evaluated for their antitubercular activities in vitro and in vivo against Mycobacterium tuberculosis H(37) Rv (MTB) and multi-drug resistant M. tuberculosis (MDR-TB). Among the synthesized compounds, 2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)-3-nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]-1,8-naphthyridine-6-carboxylic acid (10n) was found to be the most active compound in vitro with MIC of 0.19 and 0.04 microM against MTB and MTR-TB, respectively. Compound 10n showed promising activity against MDR-TB and was 208 and 1137 times more potent than gatifloxacin and isoniazid, respectively. In the in vivo animal model 10n decreased the mycobacterial load in lung and spleen tissues with 2.81 and 4.94-log(10) protections, respectively, at a dose of 50 mg/kg body weight.
以2,6 - 二甲氧基烟酸和2 - 氨基苯硫酚为原料合成了16种新型的3 - 硝基 - 2 -（取代基）- 5,12 - 二氢 - 5 - 氧代苯并噻唑并[3,2 - a] - 1,8 - 萘啶 - 6 - 羧酸，并对其针对结核分枝杆菌H(37)Rv（MTB）和耐多药结核分枝杆菌（MDR - TB）的体外和体内抗结核活性进行了评估。在合成的化合物中，2 -（1,4 - 二氧杂 - 8 - 氮杂螺[4.5]癸 - 8 - 基）- 3 - 硝基 - 5,12 - 二氢 - 5 - 氧代苯并噻唑并[3,2 - a] - 1,8 - 萘啶 - 6 - 羧酸（10n）被发现是体外活性最高的化合物，对MTB和MTR - TB的MIC分别为0.19和0.04微摩尔。化合物10n对MDR - TB显示出有前景的活性，分别比加替沙星和异烟肼强208倍和1137倍。在体内动物模型中，10n在50毫克/千克体重剂量下，使肺和脾组织中的分枝杆菌载量分别降低了2.81和4.94个对数（10）级的保护。
