ABSTRACT
The synthesis and the study of the binding affinity to human receptors of glucocorticoids, mineralcorticoids, androgens, estrogens and progesterone of 3-phenoxy-4-hydroxycoumarins and 3-phenoxy-4-phenylcoumarins were performed. It shows the absence of any binding affinity of all these derivatives to glucocorticoid and mineralcorticoid receptors and a non-selective binding affinity to androgen, oestrogen and progesterone receptors with 3-phenoxy-4-phényl-coumarins.
Subject(s)
4-Hydroxycoumarins/chemical synthesis , 4-Hydroxycoumarins/pharmacology , Coumarins/chemical synthesis , Coumarins/pharmacology , Receptors, Steroid/drug effects , Binding, Competitive/drug effects , Hormones/metabolism , Humans , Substrate SpecificityABSTRACT
The synthesis of a set of substituted 3-aryl-7-hydroxycoumarins was performed. The study of the relations between their structure and their relative binding affinity (RBA) to human alpha and B estrogen receptors was achieved.
Subject(s)
Coumarins/chemical synthesis , Receptors, Estrogen/metabolism , Cells, Cultured , Coumarins/metabolism , Estrogen Receptor alpha , Estrogen Receptor beta , Humans , Indicators and ReagentsABSTRACT
The thermal condensation of diethyl 3,4-methylenedioxyphenylmalonate with 3,5-dimethoxyphenol (di-O-methylphloroglucinol) leads to the corresponding 3-(3,4-méthylenedioxyphenyl)-4-hydroxy-5,7-dimethoxycoumarine which is methylated further into derrusnine.
Subject(s)
4-Hydroxycoumarins/chemical synthesis , Indicators and Reagents , Magnetic Resonance Spectroscopy , Spectrophotometry, InfraredABSTRACT
The biological, pharmacological and therapeutic properties of estrogens/antiestrogens are related to their chemical structure. Tamoxifen, used for the treatment of hormone-dependent breast cancer, and other analogue derivatives of triarylethylene or presenting a cyclic or heterocyclic structure, mimic some of the activities of estrogens. They have major therapeutic potential as selective estrogen receptor modulators in the prevention of breast cancer and various post-menopausal conditions.
Subject(s)
Breast Neoplasms/drug therapy , Estradiol Congeners/therapeutic use , Estrogen Receptor Modulators/therapeutic use , Estrogens/therapeutic use , Receptors, Estrogen/drug effects , Breast Neoplasms/prevention & control , Estradiol Congeners/chemistry , Estradiol Congeners/pharmacology , Estrogen Receptor Modulators/chemistry , Estrogen Receptor Modulators/pharmacology , Estrogen Replacement Therapy , Estrogens/chemistry , Estrogens/pharmacology , Female , Humans , PostmenopauseABSTRACT
The study of the relative binding affinity of a set of 2,3-disubstituted indenes to the receptors of steroid hormones indicates a weak effect of some derivatives on estrogen, progesterone and androgen receptors. The antiproliferative effect on human MCF-7 cells also shows a weak activity for three derivatives.
Subject(s)
Antineoplastic Agents/chemical synthesis , Indenes/chemical synthesis , Receptors, Steroid/metabolism , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Female , Humans , Indenes/metabolism , Indenes/pharmacology , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
The study of the relative binding affinity to steroïd hormonal receptors and of the antiproliferative action on MCF-7 cells of 3-arylcoumarines, 3-aryl-4-hydroxycoumarines, isoflavanones, isoflavan-4-ols and isoflavones, indicates a weak activity in the case of some representatives of coumarines.
Subject(s)
Coumarins/pharmacology , Isoflavones/pharmacology , Receptors, Progesterone/metabolism , Receptors, Steroid/metabolism , Adrenalectomy , Animals , Breast Neoplasms , Cell Division/drug effects , Coumarins/pharmacokinetics , Female , Humans , Isoflavones/pharmacokinetics , Kidney/metabolism , Male , Rats , Receptors, Estrogen/metabolism , Receptors, Glucocorticoid/metabolism , Receptors, Mineralocorticoid/metabolism , Recombinant Proteins/metabolism , Structure-Activity Relationship , Thymus Gland/metabolism , Tumor Cells, CulturedABSTRACT
The study of the relationships between the structure and the free radical scavenging activity of substituted 4-hydroxycoumarine derivatives, indicates the favorable effect of electron donating substituents.
Subject(s)
4-Hydroxycoumarins/chemistry , Free Radical Scavengers/chemistry , Picrates , 4-Hydroxycoumarins/pharmacology , Bepridil/analogs & derivatives , Bepridil/chemistry , Biphenyl Compounds , Free Radical Scavengers/pharmacology , Free Radicals/chemistry , Structure-Activity RelationshipABSTRACT
The study of parahydroxybenzonitrile on the cardiovascular system of the Rat shows alpha blocker properties.
Subject(s)
Blood Pressure/drug effects , Epinephrine/pharmacology , Heart Rate/drug effects , Isoproterenol/pharmacology , Norepinephrine/pharmacology , Phenylephrine/pharmacology , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Adrenergic beta-Agonists/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , RatsABSTRACT
Butyric acid is a potent antineoplastic agent with a well-documented differentiation activity on a wide variety of tumor cells. However, its clinical development is strongly limited by its very short metabolic half-life. In this study we report on the in vitro effects of new original piperazine derivatives of butyric acid on the induction of differentiation and the growth inhibition of human erythroleukemia K562 cells and myeloid leukemia HL60 cells. 1-(2-hydroxyethyl) 4-(1-oxobutyl)-piperazine (HEPB) and [1-(2-hydroxyethyl) 4-(1-oxobutyl)-piperazine] butyrate (HEPDB) were efficient in acting on the differentiation and proliferation of both cell lines, whereas 1-phenyl 4-(1-oxobutyl)-piperazine (PPB) and 1-(3,4-methylene dioxybenzyl) 4-(1-oxobutyl)-piperazine (POB) acted only on proliferation rates. Such derivatives did not induce significant toxicity in mice. These preliminary results should enable, by the development of new series of piperazine derivatives, a better understanding of the mechanisms of action of butyric acid and its analogues on the coupling of growth and differentiation of neoplastic cells.
Subject(s)
Butyrates/pharmacology , Piperazines/pharmacology , Tumor Cells, Cultured/drug effects , Animals , Butyrates/therapeutic use , Cell Division/drug effects , Humans , Lethal Dose 50 , Leukemia, Myeloid/drug therapy , Male , Mice , Structure-Activity RelationshipABSTRACT
A set of heterocyclic N-acetamidinium hydrochlorides were prepared from the corresponding N-acetonitriles. The antiparasitic screening showed that, while all amidines are practically inactive, some nitriles present leishmanicide properties.
Subject(s)
Acetonitriles/pharmacology , Amidines/pharmacology , Antiprotozoal Agents/pharmacology , Acetonitriles/chemical synthesis , Amidines/chemical synthesis , Amidines/chemistry , Animals , Antiprotozoal Agents/chemical synthesis , Leishmania donovani/drug effects , Leishmania major/drug effects , Molecular Structure , Rhabditoidea/drug effects , Trichomonas vaginalis/drug effectsSubject(s)
Antiprotozoal Agents/chemical synthesis , Antiprotozoal Agents/pharmacology , Chalcone/analogs & derivatives , Chalcone/chemical synthesis , Indoles/chemical synthesis , Indoles/pharmacology , Animals , Chalcone/pharmacology , Entamoeba histolytica/drug effects , Female , In Vitro Techniques , Trichomonas vaginalis/drug effectsSubject(s)
Antihypertensive Agents/chemical synthesis , Dioxoles/chemical synthesis , Piperazines/chemical synthesis , Animals , Antihypertensive Agents/pharmacology , Antihypertensive Agents/toxicity , Dioxoles/pharmacology , Lethal Dose 50 , Male , Molecular Structure , Piperazines/pharmacology , Piperazines/toxicity , Rats , Rats, Inbred SHRABSTRACT
The pharmacological study of 3-(4-chlorophenylsulfonyl) 4-hydroxy-7-methoxy- coumarine and 3-(4-methylphenylsulfonyl) 4-hydroxy-7-methoxy-coumarine shows that these derivatives present low sedative effects on the central nervous system, particularly due to their actions upon temperature and motility, more accentuated for the chloro-substituted derivative.
Subject(s)
4-Hydroxycoumarins/pharmacology , Vitamin K/antagonists & inhibitors , Vitamin K/pharmacology , Animals , Behavior, Animal/drug effects , Coumarins/pharmacology , Drug Interactions , Male , Mice , Mice, Inbred Strains , Psychopharmacology , Psychotropic Drugs/pharmacologyABSTRACT
The synthesis and the study of the antiparasitic properties of various 1-(nitro-phényl)-3-(méthyl-3-indolyl)-prop-2-ene-1-ones (Nitroindolylchalcones) show interesting antiprotozoal activities on E. histolytica and T. vaginalis. No significative activity appears in vivo with animals on helminthes.
Subject(s)
Chalcone/analogs & derivatives , Entamoeba histolytica/drug effects , Hymenolepis/drug effects , Nippostrongylus/drug effects , Trichomonas vaginalis/drug effects , Animals , Chalcone/chemistry , Chalcone/pharmacology , Female , In Vitro Techniques , Male , Mice , RatsABSTRACT
The pharmacological study of heterocyclic N-ethylacetic and N-ethylmalonic esters indicate a stimulating effect on central nervous system. Some derivatives show antidepressive and psychostimulant activities.
Subject(s)
Acetates/chemical synthesis , Acetates/pharmacology , Malonates/pharmacology , Acetates/toxicity , Animals , Central Nervous System/drug effects , Esters , Male , Malonates/chemical synthesis , Malonates/toxicity , MiceABSTRACT
For access to structure/activity/specificity of a serie of eight 3-benzylchromones (homoisoflavones), the authors used multivariate analysis. The obtained results allow to envisage the synthesis of molecules more specific of one of the three types of activities studied: angioprotective, antihistaminic, antiallergic.
