ABSTRACT
Ten 2-aryl or heteroaryl-3-nitrosoimidazo[1,2-a]pyridine derivatives were synthesised as potential antiretroviral agents. The new compounds were characterized by elemental analysis, 1H NMR, and by crystallography for (14). The compounds were devoid of any activity against HIV-1 or HIV-2.
Subject(s)
Anti-HIV Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Nitroso Compounds/chemical synthesis , Nitroso Compounds/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Retroviridae/drug effects , Cells, Cultured , Crystallography, X-Ray , Humans , Magnetic Resonance SpectroscopyABSTRACT
The synthesis and antiviral activity of original dibromoimidazo[1,2-a]pyridines bearing a thioether side chain are reported. Molecular modeling was used to identify biophoric structural patterns that are common to 16 compounds. Structure-activity relationship (SAR) studies identified hydrophobicity (logP) as the most important factor for activity. From these SAR studies, the antiviral activity could be predicted.
Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Pyridines/chemical synthesis , Pyridines/pharmacology , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Giant Cells/drug effects , Giant Cells/virology , HIV-1/drug effects , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Molecular Conformation , Quantitative Structure-Activity RelationshipABSTRACT
This work reports the synthesis and the antiviral activities of 3-benzamido, 3-phenylureido and 3-phenylthioureido derivatives in the imidazo[1,2-a]pyridine series. The structure was proven by NMR spectroscopy. The synthesized compounds were evaluated against a large number of viruses. The 3-phenylthioureido derivative 7 showed moderate activity against human cytomegalovirus (HCMV) in vitro. The crystallographic data for 8 are also reported and explain the absence of activity against human immunodeficiency virus (HIV).
Subject(s)
Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Imidazoles/chemical synthesis , Imidazoles/pharmacology , Phenylurea Compounds/chemical synthesis , Phenylurea Compounds/pharmacology , Thiourea/analogs & derivatives , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Cells, Cultured , Crystallography, X-Ray , Cytomegalovirus/drug effects , Humans , Magnetic Resonance Spectroscopy , Models, Molecular , Structure-Activity Relationship , Thiourea/chemical synthesis , Thiourea/pharmacology , Viral Plaque AssayABSTRACT
From the latex of Lapsana communis L. subps. communis, five guaianolide glycosides were identified: crepiside E, tectoroside and three new ones: 3-O-beta-D-glucopyranosyl-8-O-beta-acetyl-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-4(15),10(14),11(13)-triene-6,12-olide, 3-O-beta-D-glucopyranosyl-8-O-beta-acetyl-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-3(4),10(14), 11(13)-triene-15-methyl-6,12-olide, and 3-O-beta-glucopyranosyl-8-O-beta-(4-hydroxyphenyl)-lactyl-1 alpha H,5 alpha H,6 beta H,7 alpha H-guai-3(4),10(14),11(13)-triene-15-methyl-6,12-olide. Their structures were established by spectroscopic methods.
Subject(s)
Asteraceae/chemistry , Glycosides/isolation & purification , Lactones/chemistry , Sesquiterpenes/chemistry , Animals , Drug Screening Assays, Antitumor , Glycosides/chemistry , Glycosides/pharmacology , Leukemia L1210/pathology , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular StructureABSTRACT
The anticancer activity of 4-methylaminopyridol[1,2-e]purine 6a, 4-(piperidin-1-yl)pyrido[1,2-e]purine 7a and their 7-methyl derivatives 6b, 7b was investigated against the human MCF7 cancer cell line in vitro. The sensitive cell line showed a range of sensitivities to 6a, 6b, 7a, 7b (IC50: 1.6 to 7.2 x 10(-4) M) and sensitivity to doxorubicin (IC50: 7.5 x 10(-7) M). A resistant cell line with the multidrug resistant phenotype was sensitive to these derivatives (IC50: 1.8 to 6.7 x 10(-4) M), doxorubicin (IC50: 5 x 10(-5) M) and drug activity seems to be not affected by MDR resistance. Our data show that 6a, 6b, 7a and 7b appear to exert a low cytotoxicity on sensitive and MDR resistant MCF7 human cancer cell lines.
