ABSTRACT
The title compounds, that hold the deaza skeleton of temozolomide, exhibited potent in vitro antiproliferative activity. An evaluation of such a biological activity indicates that the mode of action of these compounds differs from that of temozolomide and is also mechanistically unrelated to that of any known antitumor drug.
Subject(s)
Antineoplastic Agents, Alkylating/chemical synthesis , Dacarbazine/analogs & derivatives , Heterocyclic Compounds, 2-Ring/chemical synthesis , Antineoplastic Agents, Alkylating/pharmacology , Dacarbazine/chemical synthesis , Dacarbazine/pharmacology , Heterocyclic Compounds, 2-Ring/pharmacology , TemozolomideABSTRACT
Acyclic glycosidopyrroles of type 1, synthesized in good overall yields, were evaluated for anti-viral activity. Compound 10i was found to inhibit the HIV-1 replication at concentrations that were very close to those cytotoxic for MT-4 cells. Compounds 10a,f,i inhibited both strains HSV-1 and HSV-2 at concentrations slightly below those cytotoxic for Vero cells. However for this series of glycosidopyrroles some relationship between calculated log P values and the observed cytotoxicity was found.
Subject(s)
Antiviral Agents/chemical synthesis , Pyrroles/chemical synthesis , Animals , Antiviral Agents/pharmacology , Chlorocebus aethiops , Pyrroles/pharmacology , Vero CellsABSTRACT
Acyclic glycosidopyrroles of type 3 were synthetized in good overall yields, according to the Scheme. When evaluated for antiviral activity against DNA and RNA viruses, only compound in which R1 = R2 = Ph, R3 = NH2 was found to inhibit the HIV-1 replication at concentrations that were not cytotoxic for MT-4 cells.
Subject(s)
Antiviral Agents/chemical synthesis , Ganciclovir/analogs & derivatives , Antiviral Agents/pharmacologyABSTRACT
The series of 1-(1,3-dihydroxy-2-propoxy)methylpyrroles 2a-o were prepared in good overall yields according to Scheme I. When evaluated for antiviral activity against HIV-1, only compounds of the triphenyl series (R3 = NH2, N3, Br) were found to inhibit the HIV-1 replication at concentrations that were very not cytotoxic for MT-4 cells, with selectivity index 1.5-9.3. None of these compounds showed antibacterial or antifungal activity.
Subject(s)
Anti-HIV Agents/pharmacology , Pyrroles/pharmacology , Animals , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Chlorocebus aethiops , HIV-1/drug effects , HIV-1/physiology , Humans , Pyrroles/chemical synthesis , Pyrroles/chemistry , Vero Cells , Virus Replication/drug effectsABSTRACT
The title compounds were synthesised in preparative yields by diazotization of the corresponding 2-aminopyrroles. In preliminary screening tests as antileukemic agents they showed modest activity against the murine and human leukemic cell lines FLC and K562S and their multidrug-resistant daunorubicin selected sublines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Leukemia/drug therapy , Pyrroles/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Humans , Mice , Pyrroles/pharmacology , Tumor Cells, CulturedABSTRACT
Indolo[3,2-c]cinnolines of type 5, variously substituted either in the indole and in the cinnoline moieties, were prepared in good overall yields, by intramolecular cyclization of indolo derivatives 4. Compounds 5a-d showed a good cytotoxic activity against FLC and K562 leukemic cell lines, both sensitive and multi-drug resistant.
Subject(s)
Antineoplastic Agents/chemical synthesis , Heterocyclic Compounds/chemical synthesis , Leukemia/drug therapy , Antineoplastic Agents/pharmacology , Humans , Tumor Cells, CulturedABSTRACT
Pyrrolo-, pyrazolo- and triazolo-phenanthridines were synthetized by using a Pschorrtype cyclization reaction or an intramolecular cyclization of arylnitrenium ions. By using these synthetic methods several azolo-phenanthridines, variously functionalized either in the azolo ring and in the phenanthridine moiety, were prepared. The title compounds, tested against murine leukemia cell lines, sensible and multidrug resistant, showed moderate activity with IC50 in the range 5-50 microM.
Subject(s)
Antineoplastic Agents/chemical synthesis , Phenanthridines/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Humans , Phenanthridines/pharmacologyABSTRACT
Some 3-triazenopyrroles were prepared by coupling 3-diazopyrroles and secondary amines. In preliminary in vitro screening tests derivatives 3 showed to be cytotoxic and exhibited mutagenic effects.
Subject(s)
Antineoplastic Agents/chemical synthesis , Pyrroles/chemical synthesis , Triazines/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/toxicity , Cell Survival/drug effects , Friend murine leukemia virus , Lethal Dose 50 , Leukemia, Erythroblastic, Acute/drug therapy , Melanoma, Experimental/drug therapy , Mice , Mice, Inbred DBA , Pyrroles/pharmacology , Pyrroles/toxicity , Triazines/pharmacology , Triazines/toxicity , Tumor Cells, CulturedABSTRACT
3-Diazo-2-phenylpyrroles 3a-g showed antimicrobial activity against Gram-positive bacteria, whereas against Gram-negative strains the inhibitory activity is limited to derivatives 3a and 3c. The substituents at 4 and 5 positions strongly influence the inhibitory activity, but the presence of the diazo group is crucial for appearance of activity.