ABSTRACT
2-methylfuro[2,3-g]isoquinoline-4,7,9-trione (4) and 2-methylfuro[3,2-g]isoquinoline-4,6,9-trione (5) were prepared regiospecifically from 2-azadiene 9 and bromobenzofuran-4,7-diones 1 or 11. The activity of these two compounds and some other quinonic derivatives was evaluated in vitro against a virulent strain of Toxoplasma gondii. Compounds 4 and 7 were found to be as active as pyrimethamine.
Subject(s)
Antiprotozoal Agents/chemical synthesis , Furans/chemical synthesis , Quinolines/chemical synthesis , Toxoplasma/drug effects , Animals , Antiprotozoal Agents/pharmacology , Cell Line , Furans/pharmacology , Humans , Monocytes/drug effects , Monocytes/parasitology , Quinolines/pharmacology , Toxoplasma/growth & developmentABSTRACT
The cycloaddition reactions of o-indoloquinone 4 to azadienes are described. With 1-azadiene 2, quinone 4 works as a dienophile to give the directly aromatized cycloadduct 6. In contrast, when 2-azadiene 3 is used, the cycloaddition occurs with CO-4, indicating that this system functions as a heterodienophile.
Subject(s)
Aza Compounds/chemistry , Quinones/chemistry , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
Hetero Diels-Alder reactions between 2- or 3-bromocarbazolequinones 1a or 1b and azadiene 5 afford regiospecifically pyrido[3,4-b]- and pyrido[4,3-b]carbazole-3,5,11-triones 6a and 6b. The regiochemistry of the cycloadditions is controlled by the position of the bromine atom at C-2 or C-3 of the bromoquinone. The corresponding N- and O-methyl derivatives 7 and 8 are prepared. Structural assignment of the regioisomers is made by 1H-NMR nuclear Overhauser effect difference experiments performed on a diacetoxy derivative of pyrido[4,3-b]carbazole 9b. The in vitro antifungal and antiprotozoological activities of some prepared derivatives have been evaluated against Candida albicans, Candida krusei, Cryptococcus neoformans and Trichomonas vaginalis. None of the tested compounds have shown significant activity towards the yeasts or protozoa.
Subject(s)
Antifungal Agents/chemical synthesis , Antiprotozoal Agents/chemical synthesis , Carbazoles/chemical synthesis , Animals , Antifungal Agents/pharmacology , Antiprotozoal Agents/pharmacology , Carbazoles/pharmacology , Fungi/drug effects , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Trichomonas vaginalis/drug effectsABSTRACT
Some naphtho[1,2-b]furan, furo[2,3-f], furo[2,3-g] and furo[3,2-g]quinoline derivatives have been submitted to in vitro cytotoxic tests towards L 1210, MDA-MB 231 and PC3 cell lines. Among them, the furoquinone structures exhibited the most interesting IC50 values.
Subject(s)
Antineoplastic Agents/chemical synthesis , Furans/chemical synthesis , Naphthalenes/chemical synthesis , Quinolones/chemical synthesis , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Furans/pharmacology , Humans , Naphthalenes/pharmacology , Quinolones/pharmacology , Tumor Cells, CulturedABSTRACT
The synthesis of dihydro furonaphth[1,3]oxazine derivatives 3 was performed through a Mannich-type condensation between 2-cyano-5-hydroxy-3-methylnaphtho[1,2]furan 2a, 1.5 eq of a primary amine and 3 eq of formaldehyde. Similarly, 2-cyano-5-hydroxy-3-methylfuro[2,3-f]quinoline 2b gave the dihydro furo[1,3]oxazino-quinoline compounds 4. Heating a mixture of the naphthofuran 2a, tert-butylamine and formaldehyde at toluene reflux led to the furonaphthoxazine 3e, which decomposes to afford an o-quinonemethide intermediate 5. The latter was trapped with 1-morpholinopropene to give a dihydro furonaphthopyran derivative 6. All compounds 2, 3, 4 and 6 were assayed for in vitro cytotoxic activity toward L 1210, MDA-MB 231 and PC tumor cells. Among them, furonaphth[1,3]oxazines 3b, 3c, and furo[1,3]oxazinoquinolines 4c, 4d showed significant activity against L 1210 cells, while furoquinoline 2b was the most cytotoxic compound towards all three cell lines.
Subject(s)
Antineoplastic Agents/chemical synthesis , Oxazines/chemical synthesis , Quinolines/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Humans , Leukemia L1210/drug therapy , Oxazines/pharmacology , Quinolines/pharmacology , Tumor Cells, CulturedABSTRACT
Some 1,4-dihydro aza- and 1,4-dihydro diazaanthraquinone derivatives have been synthesized and submitted to in vitro cytotoxicity tests towards L 1210, MDA-MB 231 and PC3 cell lines. Some of the new substances showed significant activity.
Subject(s)
Anthraquinones/chemical synthesis , Antineoplastic Agents/chemical synthesis , Animals , Anthraquinones/pharmacology , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Female , Humans , Leukemia L1210/drug therapy , Male , Mice , Tumor Cells, CulturedSubject(s)
Antineoplastic Agents/chemical synthesis , Furans/chemical synthesis , Hydrazones/chemical synthesis , Animals , Antineoplastic Agents/pharmacology , Drug Screening Assays, Antitumor , Furans/pharmacology , Humans , Hydrazones/pharmacology , Leukemia L1210/drug therapy , Mice , Tumor Cells, CulturedSubject(s)
Antineoplastic Agents/pharmacology , Naphthols/pharmacology , Nitrogen Mustard Compounds/pharmacology , Animals , Cystadenoma/drug therapy , Female , Humans , Leukemia L1210/drug therapy , Male , Mice , Neoplasm Transplantation , Ovarian Neoplasms/drug therapy , Tumor Cells, Cultured/drug effectsSubject(s)
Antifungal Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Furans/chemical synthesis , Oxazines/chemical synthesis , Animals , Fungi/drug effects , Furans/pharmacology , Humans , Leukemia L1210/drug therapy , Microbial Sensitivity Tests , Oxazines/pharmacology , Tumor Cells, CulturedSubject(s)
Antineoplastic Agents/chemical synthesis , Naphthoquinones/chemical synthesis , Adenoma/drug therapy , Adult , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Ehrlich Tumor/drug therapy , Cystadenoma/drug therapy , Cystadenoma/pathology , Female , Humans , Mammary Neoplasms, Experimental/drug therapy , Mice , Mice, Inbred Strains , Naphthoquinones/pharmacology , Neoplasm Transplantation , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/pathologyABSTRACT
Mannich bases of 5-hydroxynaphthalene-1,8-carbolactone 1 were prepared from various secondary amines or bulky primary amines and formaldehyde. They were isolated in almost all cases as hydrochlorides. These derivatives were submitted to in vitro antifungal and cytotoxic assays. The antifungal assays were performed against three strains of yeasts and five strains of human pathogenic fungi. Two of the tested compounds, 2i and 2j, exhibited interesting antifungal activities against Candida albicans and Candida tropicalis. The cytotoxic activity was evaluated towards L 1210 leukemia cells. Almost all of the Mannich bases had shown significant activity against this tumor cell line as values of IC50 less than or equal to 4 micrograms/ml are considered interesting. Only one derivative 2 developed better cytotoxicity than the parent compound 1.
Subject(s)
Antifungal Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Lactones/chemical synthesis , Mannich Bases/chemical synthesis , Naphthols/chemical synthesis , Animals , Fungi/drug effects , Lactones/pharmacology , Leukemia L1210/drug therapy , Mannich Bases/pharmacology , Microbial Sensitivity Tests , Naphthols/pharmacologyABSTRACT
Tetrahydronaphthoquinones and tetrahydroanthraquinones bearing an amido group have been prepared by Diels-Alder reactions between (E)-1-(N-carbobenzyloxyamino)-1,3-butadiene (2) or (E)-1-(N-benzoyl-N-benzylamino)-1,3-butadiene (5) and benzoquinone or 5-substituted naphthoquinones. The stereochemistry of the cycloadditions was investigated. A high regioselectivity was observed in the reaction of the diene carbamate 2 with 5-methoxy and 5-acetoxy naphthoquinones. This latter gave the unexpected 1,8-regioisomer 3d. The cycloadditions of the dienamide 5 with naphthoquinones 1 (R = OH, OMe, OAc) are regiospecific. Assignment of the structure of the tetrahydroanthraquinone 6b is in good agreement with the known directing effect of the 5-hydroxy group of juglone 1b in analogous Diels-Alder reactions. With 5-methoxy and 5-acetoxy naphthoquinones, the opposite regiochemistry observed is consistent with the electron-donating influence of the methoxy or acetoxy group, making the C-3 carbon atom more electron deficient. Aromatization of the adducts 6b and 7c was accompanied by an unusual elimination of the amido moiety. Thus, 1-hydroxy and 1-methoxy anthraquinones were obtained. Reactions of the dienes 2 and 5 with benzoquinone gave the tetrahydronaphthoquinones 9 and 10 with an endo stereospecificity. Oxidation of 9 by activated manganese dioxide gave the naphthoquinone 11. These compounds were submitted to in vitro cytotoxic assays towards murine L 1210 leukemia cells and clonogenic human tumor cell line MDA-MB 231. The naphthoquinone derivatives 9, 10 and 11 had significant activities with IC50 less than or equal to 0.4 microgram/ml towards these two tumor cell systems.
Subject(s)
Amides/chemical synthesis , Anthraquinones/chemical synthesis , Antineoplastic Agents/chemical synthesis , Cell Survival/drug effects , Naphthoquinones/chemical synthesis , Amides/pharmacology , Animals , Anthraquinones/pharmacology , Chemical Phenomena , Chemistry , Humans , Mice , Naphthoquinones/pharmacology , Tumor Cells, Cultured/drug effectsABSTRACT
Naphthalene-1,8 carbolactone derivatives have been investigated in order to compare their activities using antitumoral, antibacterial and antifungal tests in vitro. The effect of 5-substitution is the reduction of the toxicity and the suppression of the antibiotic activity. The best results were obtained with the ester series (5-acetoxy and 5-propionyloxy) on both antitumoral and antifungal tests.
Subject(s)
Anti-Infective Agents/chemical synthesis , Antifungal Agents/chemical synthesis , Antineoplastic Agents/chemical synthesis , Lactones/chemical synthesis , Naphthalenes/chemical synthesis , Animals , Carbamates/chemical synthesis , Carbamates/pharmacology , Cell Survival/drug effects , Chemical Phenomena , Chemistry , Clone Cells , Humans , Lactones/pharmacology , Leukemia L1210/drug therapy , Microbial Sensitivity Tests , Naphthalenes/pharmacologySubject(s)
Antineoplastic Agents/pharmacology , Lactones/pharmacology , Naphthalenes/pharmacology , Animals , Antineoplastic Agents/analysis , Carbamates/analysis , Carbamates/pharmacology , Carcinoma, Ehrlich Tumor/drug therapy , Chemical Phenomena , Chemistry, Physical , Lactones/analysis , Leukemia L1210/drug therapy , Mice , Naphthalenes/analysis , Structure-Activity Relationship , Tumor Cells, Cultured/drug effectsSubject(s)
Antineoplastic Agents/chemical synthesis , Naphthols/chemical synthesis , Tumor Cells, Cultured/drug effects , Adenocarcinoma/pathology , Animals , Antineoplastic Agents/pharmacology , Carcinoma, Ehrlich Tumor/pathology , Mammary Neoplasms, Experimental/pathology , Mice , Naphthols/pharmacologyABSTRACT
The important discovery by Pasteur of optical isomerism and the recent developments of stereochemistry showed that a complementarity exist between the geometry of molecules and their pharmacological receptors. The stereochemical bases and the principal configurational nomenclatures are briefly overviewed. The stereospecificity of the biological response and theories leading to an approach to stereochemical structures of main pharmacological receptors are developed. So, the biological activity of steroids is due to junctional modes of cycles and alpha or beta configurations of substituents. Acetylcholine has a skew conformation but it react by an anticlinal/anti-planar conformation with muscarinic receptor. To explain the difference in activity of adrenaline enantiomers, Easson and Stedman proposed a "three points" fixation to the adrenergic receptor. Dopaminergic receptor present a good degree of stereoselectivity: dopamine act by an anti-planar conformation in which the N-O distance is the same as in apomorphine (N-O10). The analgesic activity of morphinans is due to a cis junction of B and C cycles and to the stereoelectronic effect of the unshared lone pair on nitrogen. In the cyclamate sweeteners, some authors proposed for the sweet taste receptor a model with two points fixation (one acceptor and one donor) and two spatial barriers located at precise distances from this two sites. The stereoselectivity of molecules acting as substrates or inhibitors of enzymes is described. For example some oxazolidinone derivatives showed a selective inhibition toward monoamine oxidase A. Finally, the pharmacological activity falls often when molecules are administrated in racemic form. It seems that xenobiotics need to be dissymmetric for chiral recognition by biological systems.