ABSTRACT
The preparation of new analogues of lignans carrying an imidazole ring has been achieved. Starting from L-histidinol, cis and trans stereoisomers have been obtained. The synthesized products lack the cytotoxicity displayed by related podophyllotoxins and azatoxin.
Subject(s)
Lignans/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Division/drug effects , Heterocyclic Compounds/chemical synthesis , Heterocyclic Compounds/pharmacology , Humans , Lignans/chemical synthesis , Pyridines/chemical synthesis , Pyridines/pharmacology , Structure-Activity Relationship , Tumor Cells, Cultured/drug effectsABSTRACT
Two new indolocarbazole alkaloids, 4'-N-methyl-5'-hydroxystaurosporine (2) and 5'-hydroxystaurosporine (3), were isolated together with the known staurosporine (1) from the culture broth of a marine Micromonospora sp. (strain L-31-CLCO-002). The fermentation, structural data and cytotoxic activities of these compounds against various tumor cell lines are given.
Subject(s)
Antineoplastic Agents/isolation & purification , Carbazoles/isolation & purification , Indoles/isolation & purification , Micromonospora/chemistry , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/pharmacology , Animals , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Carbazoles/chemistry , Carbazoles/pharmacology , Drug Screening Assays, Antitumor , HT29 Cells , Humans , Indoles/chemistry , Indoles/pharmacology , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mice , Micromonospora/growth & development , Micromonospora/metabolism , Staurosporine/analogs & derivatives , Tumor Cells, Cultured , Water MicrobiologyABSTRACT
Taking into account the structure of Combretastatins, we have synthesized and assayed for cytotoxic activity of new indole derivatives. Two aryl groups are maintained in the cis orientation required for activity by means of an indole moiety built up on less active ketoderivatives used as starting materials.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Antineoplastic Agents, Phytogenic/pharmacology , Bibenzyls/chemical synthesis , Bibenzyls/pharmacology , Stilbenes , Antineoplastic Agents, Phytogenic/chemistry , Bibenzyls/chemistry , Drug Screening Assays, Antitumor , Humans , Tumor Cells, CulturedABSTRACT
The hexane extract of aerial parts of Santolina rosmarinifolia subsp. canescens afforded eight new sesquiterpenes in addition to known compounds. Their structures were determined by spectroscopic methods and chemical transformations. The conformational analysis of the germacrane constituents was carried out by spectroscopic methods, including NMR at varying temperature and by molecular mechanics calculations. The antifeedant, antibacterial and antitumoral activity of selected compounds has been tested.
Subject(s)
Asteraceae/chemistry , Sesquiterpenes/chemistry , Animals , Anti-Infective Agents/chemistry , Anti-Infective Agents/isolation & purification , Anti-Infective Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Mass Spectrometry , Mice , Microbial Sensitivity Tests , Molecular Structure , Sesquiterpenes/isolation & purification , Sesquiterpenes/pharmacology , Tumor Cells, CulturedABSTRACT
Several chloro- and iodo-lignanolides have been obtained by direct halogenation of aromatic rings from yatein and 4'-O-demethylyatein. They were assayed as antineoplastics, in order to check the influence in the activity of substitution in both aromatic rings. Although these compounds show a modest antineoplastic activity, it is far from that displayed by yatein and podophyllotoxin. These results confirm that demethylation and the introduction of halo substituents diminish the activity of lignans of the dibenzylbutyrolactone type.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Antiviral Agents/chemical synthesis , Antiviral Agents/pharmacology , Lignans/chemical synthesis , Lignans/pharmacology , Animals , Antineoplastic Agents/chemistry , Antiviral Agents/chemistry , Drug Evaluation, Preclinical , Humans , Lignans/chemistry , Molecular Structure , Tumor Cells, CulturedABSTRACT
A new class of heteroaromatic analogs of lignans, called heterolignanolides, have been tested against several tumor cell lines. These compounds carry diverse heterocyclic rings, instead of the trimethoxyphenyl ring found in the natural lignans yatein and podorhizol. They have moderate antineoplastic activity (P-388, A-549, HT-29) compared with that of yatein. None of the tested compounds has discernible antiviral (HSV-1, VSV) or enzyme inhibitor (ADA, DHFR, GST) activity.
