Newer tetracycline derivatives: synthesis, anti-HIV, antimycobacterial activities and inhibition of HIV-1 integrase.
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.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani 333031, India. dsiram@bits-pilani.ac.in
Yogeeswari
Perumal
P
Senchani
Geetha
G
Banerjee
Debjani
D
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D024841:Fluoroquinolones; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013754:Tetracyclines / Q000138:chemical synthesis* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D024841:Fluoroquinolones; D019428:HIV Integrase Inhibitors; D013754:Tetracyclines