ABSTRACT
BACKGROUND: It is generally accepted that morphine affords cardioprotection against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability transition pore (MPTP) is considered an end target for cardioprotection. The aim of this study was to investigate the involvement of opioid receptors (OR) and MPTP in morphine-induced postconditioning (M-Post). METHODS: Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 1 microM morphine, with or without the OR antagonists or a MPTP opener at early reperfusion. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining. RESULTS: There were no significant differences in cardiodynamic variables except a decrease in heart rate in the M-Post group (P 0.05). The nonspecific OR antagonist naloxone (25.7 +/- 1.9%, P < 0.01), the delta-OR antagonist naltrindole (27.8 +/- 4.3%, P < 0.05) and delta1-OR antagonist 7-benzylidenenaltrexone (24.7 +/- 3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post. In addition, the anti-infarct effect by M-Post was also totally blocked by the MPTP opener atractyloside (26.3 +/- 5.2%, P < 0.05). CONCLUSIONS: M-Post effectively reduces myocardial infarction. The anti-infarct effect by M-Post is mediated via activation of delta-OR, especially delta1-OR, and inhibition of the MPTP opening.
Subject(s)
Animals , Rats , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine , Atractyloside , Benzylidene Compounds , Heart , Heart Rate , Ischemia , Ischemic Postconditioning , Mitochondrial Membrane Transport Proteins , Morphine , Myocardial Infarction , Naloxone , Naltrexone , Permeability , Receptors, Opioid , Reperfusion , Reperfusion Injury , Tetrazolium SaltsABSTRACT
<p><b>AIM</b>To design and synthesize new compounds of prandial glucose regulator with more simple structure.</p><p><b>METHODS</b>The target compounds were synthesized from diethyl succinate and benzaldehyde or 4-fluorobenzaldehyde by four-step reactions. Thus 18 compounds were synthesized. Their structures were comfirmed by NMR, MS and IR.</p><p><b>RESULTS</b>Seventeen compounds had different hypoglycemic activity in mice, among them, 9 compounds had higher hypoglycemic activity and 6 compounds had character of prandial glucose regulator.</p><p><b>CONCLUSION</b>Part of the compounds have higher hypoglycemic activity deserve to be further investigated.</p>
Subject(s)
Animals , Mice , Benzylidene Compounds , Chemistry , Pharmacology , Blood Glucose , Metabolism , Carbamates , Chemistry , Cyclohexanes , Chemistry , Hypoglycemic Agents , Chemistry , Pharmacology , Indoles , Chemistry , Isoindoles , Molecular Structure , Phenylalanine , Chemistry , Piperidines , Chemistry , Structure-Activity Relationship , Succinates , Chemistry , PharmacologyABSTRACT
<p><b>AIM</b>To study the structure and crystal forms of chlorobenzylidine.</p><p><b>METHODS</b>Karl Fischer titrimetry, FTIR, thermal analysis, single and powder X-ray diffraction were used for the studies of the structure of chlorobenzylidine and for the identification of two forms of chlorobenzylidine.</p><p><b>RESULTS</b>Chlorobenzylidine and its diastereoisomer have been studied in this article. They can be distinguished by their different melting points. Two crystal forms of chlorobenzylidine (form A and form B) have also been detected and studied. Form A was studied by single-crystal X-ray diffraction, it crystallized in the triclinic system, space group P1(-), with two formula units per cell, is monohydrate. Karl Fischer titrimetry, FTIR, thermal analysis and powder X-ray diffraction were used for identification of the two forms.</p><p><b>CONCLUSION</b>The studies of structure and crystal forms of chlorobenzylidine are very useful for the clinical research and the selection of recrystallization process.</p>
Subject(s)
Benzylidene Compounds , Crystallization , Crystallography, X-Ray , Differential Thermal Analysis , Molecular Conformation , Molecular Structure , Polycyclic Compounds , Chemistry , StereoisomerismABSTRACT
A series of E-2-benzylidene-1-indanones and E-2-benzlididene-1-benzosuberones were synthesized to investigate their in vitro antifungal activity against 24 strains belonging to important human pathogenic yeasts, such as Cryptococcus neoformans, Candida spp. and Trichosporon cutaneum. These strains were shown to be resistant to miconazole and isoconazole. There was a diversity in response among the different strains. Many of the compounds tested were shown to have good activity and many had minimum inhibitory concentrations [MICs] of 6 micro g/ml or lower against most of the strains. The standard systemic and topical commercial drugs also showed a great degree of diversity, exhibiting MICs that ranged from 6 to >100 micro g/ml against the same yeast strains. The in vivo toxicity of the synthesized compounds tested by an acute toxicity procedure in mice [MFI strain] and the in vitro activity in HeLa cells suggests that most of the active compounds were of lower toxicity, while only a few were of a toxicity similar to that of the least toxic commercial antifungal agent investigated in our animal and cell culture modles [amphotericin B]. The relatively low LD50 and good MIC values of most of our compounds in comparison to the least toxic and most active commercial agents tested [amphotericin B and haloprogin, respectively] justifies the testing of these synthetic agents for further development
Subject(s)
Antifungal Agents , Benzylidene Compounds/chemistryABSTRACT
The charge transfer complexes formed between some benzylidine aniline derivatives and p-benzoquinones have been investigated conductimetrically. The results indicate the formation of 1:1 and 1:2 [D: A] complexes. The stoichiometric conductance sigma p and molar conductance of the complexes have been calculated at 22 degree. The effects of electron affinity of the acceptor, ionization potential of the donor and temperature have been investigated and discussed
Subject(s)
Benzylidene Compounds/analysis , Schiff Bases , BenzoquinonesABSTRACT
The carbanions of several dithioacetals of aromatic aldehydes were treated with nitrochlorobenzenes, alpha-chloroacetic acid and beta- bromopropionic acid to give nucleophilic substitution products. The postulated mechanism is discussed as an aromatic nucleophilic reaction in which the halogen atom was replaced by sulfur containing carbanions. Vicarious nucleophilic substitution reactions for nitroaromatic rings were excluded, due to the occupation of p- position and steric factor
Subject(s)
Benzylidene Compounds/chemistryABSTRACT
Oral treatment of compound IIIA exhibited dose related inhibitory action in acute tests of carrageenan, histamine and dextran-induced oedema in rats. Marked inhibitory action of the compound was found when it was administered intraperitoneally in animals. It displayed prominent anti-arthritic activity in chronic tests of adjuvant and formaldehyde-induced arthritis in rats. It prevented the arthritis associated rise in total leucocyte count and erythrocyte sedimentation rate. It also lowered the levels of exudate volume and migration of leucocytes in carrageenan induced pleurisy in rats. It did not exhibit any analgesic, antipyretic or ulcerogenic effect. No mortality was recorded up to 2 g/kg in mice on oral or intraperitoneal treatment over a period of 72 hr.
Subject(s)
Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Benzylidene Compounds/pharmacology , Female , Male , Mice , Pyrazolones , Rats , Rats, Inbred StrainsABSTRACT
Fifty-five new compounds belonging to the naturally occurring benzylidene chromanones were synthesised and their activity against the important human pathogenic yeasts Cryptococcus neoformans, Candida spp., Trichosporon cutaneum and Torulopsisgh brata was assessed in vitro using a microtitre technique. These yeasts had already been found resistant to miconazole, at a minimum inhibitory concentration [MIC] of 100 micro g/ml or more The structural differences between the molecules of the new compounds, such as their three dimensional shape, the presence of oxygen or sulphur hetero-atoms, or a cyclic bridge, were studied to establish models for their structure-to-antimycotic activity. Twenty-eight of the compounds were found active against the tested yeasts and had an MIC of 6 micro g/ml. There was a heterogeneity in the response of the yeasts to the active compounds, which could be linked to structural factors in C. neoformans
Subject(s)
Fungi/drug effects , Benzylidene Compounds , Miconazole/pharmacologyABSTRACT
The mechanism of formation of benzylidene derivatives was deduced from the mode of the condition of benzylidenation as well as from their assigned structures. The absolute configuration has been assigned to the various isomeric forms for each diastereoisomer. The protection of hydroxyl groups in a polyhydroxymolecule can be achieved by various ways, e.g. by acylation and/or acetalization. The latter protecting groups possess the advantage, in most cases, of being stable towards, alkaline conditions but could be successively cleaved under acidic conditions, whereas, the acylated products possesses a reverse character. Acetalization may promise the direct protection of two hydroxyl groups out of three or more existing in the same molecule. Perprotection of the hydroxyl groups can be easily accomplished without much problems, whereas their partial protection needs much care and it is very important in organic synthesis