Nitroimidazoles, part 2: Synthesis, antiviral and antitumor activity of new 4-nitroimidazoles.

Abstract

A series of 5-alkylamino and 5-alkylsulfanyl derivatives of 1-aryl-2-alkyl-4-nitro-1H-imidazoles 12-21, 31, and 34 were synthesized by a simple method with the aim to develop novel HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs). All the new compounds were tested against HIV-1 and HIV-2 in MT-4 cells. Compound 21, with an arylsulfanyl group at C(5) of the 4-nitro-1H-imidazole backbone showed an EC(50) value of 0.22 microg/ml against HIV-1 with a therapeutic index of 13. This means that compound 21 was cytotoxic to MT-4 cells at a CC(50) value of 2.57 microg/ml; also compounds 8, 22-25, 28, and 29 were cytotoxic to MT-4 cells within the 0.4-4 microg/ml concentration range. Compounds 8, and 12-21 were evaluated, as a rule, but found inactive at non-toxic concentrations against hepatitis C virus, herpes simplex type 1 and 2, cytomegalovirus (CMV), varicella-zoster virus (VZV), vaccinia virus, and vesicular stomatitis virus, and a number of other viruses. Yet, the therapeutic index of compounds 17 and 21 for CMV and VZV approached the tenfold cut-off point. Compounds 8 and 21 exhibited some cytostatic activity against leukemia and melanoma cell lines.

• Authors: Najim A Al-Masoudi, Yaseen A Al-Soud, Aris Kalogerakis, Christophe Pannecouque, Erik De Clercq
• Journal: Chemistry & biodiversity (Chem Biodivers) Vol. 3 Issue 5 Pg. 515-26 (May 2006) ISSN: 1612-1880 [Electronic] Switzerland
• PMID: 17193287 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Nitroimidazoles

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytomegalovirus (drug effects)
• HIV (drug effects)
• Hepacivirus (drug effects)
• Humans
• Magnetic Resonance Spectroscopy
• Molecular Structure
• Nitroimidazoles (chemical synthesis, chemistry, pharmacology)