新型四环素衍生物：合成、抗HIV、抗分枝杆菌活性及对HIV-1整合酶的抑制作用

Newer tetracycline derivatives: synthesis, anti-HIV, antimycobacterial activities and inhibition of HIV-1 integrase.

作者信息

Sriram Dharmarajan, Yogeeswari Perumal, Senchani Geetha, Banerjee Debjani

机构信息

Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani 333031, India.

出版信息

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2372-5. doi: 10.1016/j.bmcl.2006.11.055. Epub 2006 Nov 19.

DOI:10.1016/j.bmcl.2006.11.055

PMID:17376679

Abstract

A series of new tetracycline derivatives has been synthesized by reacting appropriate tetracyclines, formaldehyde and secondary amino (piperazino) function of fluoroquinolones using microwave irradiation with the yield ranging from 41 evaluated for its anti-HIV, antimycobacterial activities and HIV-1 integrase (IN) enzyme inhibition studies. Among the synthesized compounds, compound 10 was found to be the most promising compound active against HIV-1 replication with EC(50) of 5.2 microM and was nontoxic to the CEM cells until 200 microM, and MIC of 0.2 microg/mL against Mycobacterium tuberculosis, with moderate inhibition of both 3'-processing and strand transfer steps of HIV-1 IN.

摘要

通过使用微波辐射使适当的四环素、甲醛和氟喹诺酮的仲氨基（哌嗪基）官能团反应，合成了一系列新的四环素衍生物，产率在41%范围内。对其进行了抗HIV、抗分枝杆菌活性以及HIV-1整合酶（IN）酶抑制研究。在合成的化合物中，化合物10被发现是最有前景的抗HIV-1复制活性化合物，其EC(50)为5.2 microM，在200 microM浓度下对CEM细胞无毒，对结核分枝杆菌的MIC为0.2 microg/mL，对HIV-1 IN的3'-加工和链转移步骤均有适度抑制作用。