Synthesis and anti-HIV-1 activity of N-hydroxy-N1-aminoguanidines.
The synthesis of 13 new Schiff bases of N-hydroxy-N1-aminoguanidines starting from thiosemicarbazide are reported. These new derivatives were for the first time tested against infection by the Human Immunodeficiency Virus Type 1 (HIV-1) using the human T-lymphocyte cell line. Four N-hydroxy-N1-aminoguanidines exhibited HIV-1 inhibition in the micromolar range. The most active compound, [1-(1'-chloro-2'-hydroxy-3'-methoxybenzylidene)amino]-3-hydroxy guanidine inhibited HIV-1 by 96% at 10 micrograms/ml concentration. All the derivatives exhibited substantial cytotoxicity at 320 micrograms/ml concentration. The results indicate that the activity against HIV-1 increases with increasing hydrophobicity and substituents with electron-donating properties.
Doubell
P C
PC
Department of Pharmaceutical Chemistry, Pretoria College of Pharmacy, University of Pretoria, Republic of South Africa.
Oliver
D W
DW
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D006146:Guanidines / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D012545:Schiff Bases / Q000737:chemistry; D013601:T-Lymphocytes / Q000382:microbiology; D015215:Zidovudine / Q000494:pharmacology
D000998:Antiviral Agents; D006146:Guanidines; D012545:Schiff Bases; D015215:Zidovudine