Ten novel compounds were designed and synthesized on the basis of compound 1, their insulin-sensitizing activities were evaluated in 3T3-L1 cells. Results showed that compound 10 exhibited strong differentiation-stimulating activity on 3T3-L1 cells model, which indicated that compound 10 may possess well insulin-sensitizing activity.
3T3-L1 Cells ; Animals ; Benzopyrans ; chemical synthesis ; pharmacology ; Drug Design ; Hypoglycemic Agents ; chemical synthesis ; pharmacology ; Insulin ; pharmacology ; Mice

A series of novel N-acyl-thiochromenothiazol-2-amine derivatives were designed and synthesized, furthermore, their inhibition effect on acetylcholinesterase was investigated. N-Acyl-thiochromenothiazol-2-amines were prepared from thiophenol by Hantzsch reaction, acylation reaction and substitution reaction. Moreover, their bioactivities as AChE inhibitors in vitro were measured with Ellman spectrophotometry. The results showed that most of them had a certain inhibition activity on AChE, and the compound 10a was the best in them. The IC50 of 10a to AChE is 7.92 μmol x L(-1), and the value is better than that of rivastigmine. N-Acyl-thiochromenothiazol-2-amine derivatives showed a certain bioactivity in vitro, which were worth further investigation.
Acetylcholinesterase ; metabolism ; Amines ; chemical synthesis ; pharmacology ; Benzopyrans ; chemical synthesis ; pharmacology ; Cholinesterase Inhibitors ; chemical synthesis ; pharmacology ; Rivastigmine ; Structure-Activity Relationship ; Thiazoles ; chemical synthesis ; pharmacology

A new chromene (1) and six known compounds identified as 6-hydroxymellein (2), 6-hydroxy-5-methylmellein (3) nectriapyrone (4), chermesinone A(5), chermesinone B(6), and pomopxanthone A(7), were isolated in our investigation of the cytotoxic constituents from the fermented rice substrate of endophytic fungus Phomopsis sp. HCCB03519. The structures of these com pounds were elucidated through spectroscopic data analysis. All compounds exhibited inhibitory activities against cancer cell lines. Compound 7 showed stronger inhibition against cancer cells than the positive control 5-Fu.
Antineoplastic Agents ; chemistry ; pharmacology ; Ascomycota ; chemistry ; Benzopyrans ; chemistry ; pharmacology ; Cell Line, Tumor ; Fluorouracil ; chemistry ; pharmacology ; Humans ; Isocoumarins ; chemistry ; pharmacology ; Molecular Structure

Previous studies have demonstrated that rottlerin, a specific PKCdelta inhibitor, potentiates death receptor- mediated apoptosis through a cytochrome c-dependent or -independent pathway. However, its ability to regulate necrotic cell death, as well as the underlying mechanism, remains unknown. We found that in murine fibrosarcoma L929 cells, treatment with rottlerin protected the cells against TNF-induced necrosis, whereas it sensitized the cells to apoptosis induced by co-treatment with Hsp90 inhibitor geldanamycin and TNF, in a manner independent of its ability to inhibit PKC-delta. TNF treatment induced rapid accumulation of mitochondrial superoxide (O2") through the Nox1 NADPH oxidase when cells undergo necrosis. Moreover, pretreatment with rottlerin failed to induce the GTP-bound form of small GTPase Rac1 by TNF treatment, and subsequently suppressed mitochondrial O2(-) production and poly(ADP-ribose) polymerase activation, thus inhibiting necrotic cell death. Therefore, our study suggests that Nox1 NADPH oxidase is a new molecular target for anti-necrotic activity of rottlerin upon death-receptor ligation.
Acetophenones/*pharmacology ; Animals ; Benzopyrans/*pharmacology ; Cell Death/*drug effects ; Cell Line, Tumor ; Mice ; Protein Kinase Inhibitors/*pharmacology ; Superoxides/metabolism ; Tumor Necrosis Factor-alpha/*antagonists & inhibitors/pharmacology

AIMIn search of more potent, less toxic and selective potassium channel openers.

METHODSAccording to the structure-activity relationships of benzopyran compounds and the features of structures of aprikalim, dofetilide and nifekalant, twenty benzopyran-4-one hydrazone derivatives have been designed and synthesized from 4-cyanophenos through acetylation, Fries rearrangment, cyclization, hydrazone, substitution reaction and so on. The compounds were tested for their vasorelaxant activity in low (30 mmol.L-1) and high (80 mmol.L-1) KCl-induced contraction of rat aorta to identify potential potassium channel openers in vitro.

RESULTSThree series of twenty benzopyran-4-one hydrazone derivatives, nominated N-aminoacetyl-(6-cyano-3,4-dihydrospiro [2H-1-benzopyran-2,1'-cyclohexane]-4)-one hydrazone (I), 2-(6-cyano-3, 4-dihydro-2H-1-benzopyran-4-ylene) hydrazinethiocarboxamide derivatives (II) and N-(2-arylethyl) aminoacetyl-(6-cyano-3,4-dihydro-2H-1-benzopyran)-4-one hydrazone (III), have been synthesized. They (I1-9, II1-4 and III1-7) are new compounds. Their chemical structures were determined by IR, 1HNMR, MS and elemental analysis. The vasorelaxant effects of those novel compounds indicated that some of the compounds have vasorelaxant activities at 1 x 10(-6) mol.L-1.

CONCLUSIONThe vasorelaxant activities of compounds I9, III2 and III5 in inhibiting low KCl-induced vasocontraction at 1 x 10(-6) mol.L-1 are less potent than the reference compound emakalim. However they are more potent than emakalim to inhibition high concentration KCl-induced vasocontraction at 1 x 10(-5) mol.L-1. It is worthy of further study.

Animals ; Aorta ; drug effects ; Benzopyrans ; chemical synthesis ; pharmacology ; Molecular Structure ; Potassium Channels ; agonists ; Rats ; Vasodilation ; drug effects ; Vasodilator Agents ; chemical synthesis ; pharmacology

This study was performed to investigate the action of potassium channel openers on the mechanical activity of detrusor muscle isolated from rats. Detrusor muscle strips, 15 mm in length, were myographied isometrically in an isolated organ bath. P 1060, RP 49356 and BRL 38277, potassium channel activators, reduced the basal tone and diminished the phasic activity of detrusor concentration-dependently. P 1060, RP 49356 and BRL 38227 suppressed the maximal responses to bethanechol and shifted the concentration-response curves of bethanechol-induced contraction to the right. RP 49356 and BRL 38227 reduced the contraction by low (20 mM) concentration of potassium. P 1060, however, diminished the high (80 mM) and low (20 mM) concentration of potassium-induced contraction. Glibenclamide, an inhibitor of ATP-dependent potassium channel, antagonized the suppressive action of P 1060, RP 49356 and BRL 38227 on the basal tone. Apamin or procaine did not antagonize it significantly. Based on these results, it is suggested that the relaxation of detrusor muscle strip caused by P 1060, RP 49356 and BRL 38227 may predominantly involve opening of the same potassium channel, i.e., the ATP-dependent potassium channel.
Animals ; Benzopyrans/*pharmacology ; Cromakalim ; Guanidines/*pharmacology ; Muscle Contraction/drug effects ; Muscle, Smooth/*drug effects ; Picolines/*pharmacology ; Potassium Channels/*drug effects ; Pyrans/*pharmacology ; Pyrroles/*pharmacology ; Rats ; Rats, Sprague-Dawley ; Urinary Bladder/*drug effects/physiology

In order to investigate the impact of fulvic acid (FA) on the hydroxylysyl glycosylation in collagen bio-synthesis, 40 NMRI mice were divided into two groups (n = 20 in each group, consisting 10 females and 10 males). The animal was maintained for two generations by different diets: control group with normal water and food and study group with water containing 30 mg/L FA and normal food. The second generation of the animal was slaughtered, and the biochemical parameters of collagen content and the degree of collagen hydroxylysyl glycosylation in skin, rib and tibia were detected by biochemical methods. The mean value of collagen in the study group was increased slightly, and no significant difference between study group and control group was found (P > 0.05), but the content of glucose-glactose-hydroxylysine (GGH) was significantly decreased in the study group in comparison with the control group (P<0.01). It was suggested that through the decrease of GGH 30 mg/L FA could inhibit the activity of galactosyl-hydroxylysylglucosyl-transferase and further disturb the post-translational modification of collagen intracellularly.
Animals ; Benzopyrans ; pharmacology ; Bone Development ; Bone and Bones ; chemistry ; metabolism ; Collagen ; biosynthesis ; Female ; Glycosylation ; Hydroxylysine ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Osteoarthritis ; etiology ; Selenium ; deficiency

In order to investigate the impact of fulvic acid (FA) on the hydroxylysyl glycosylation in collagen bio-synthesis, 40 NMRI mice were divided into two groups (n = 20 in each group, consisting 10 females and 10 males). The animal was maintained for two generations by different diets: control group with normal water and food and study group with water containing 30 mg/L FA and normal food. The second generation of the animal was slaughtered, and the biochemical parameters of collagen content and the degree of collagen hydroxylysyl glycosylation in skin, rib and tibia were detected by biochemical methods. The mean value of collagen in the study group was increased slightly, and no significant difference between study group and control group was found (P > 0.05), but the content of glucose-glactose-hydroxylysine (GGH) was significantly decreased in the study group in comparison with the control group (P<0.01). It was suggested that through the decrease of GGH 30 mg/L FA could inhibit the activity of galactosyl-hydroxylysylglucosyl-transferase and further disturb the post-translational modification of collagen intracellularly.
Benzopyrans/*pharmacology ; Bone Development ; Bone and Bones/chemistry ; Bone and Bones/*metabolism ; Collagen/*biosynthesis ; Glycosylation ; Hydroxylysine/*metabolism ; Mice, Inbred Strains ; Osteoarthritis/etiology ; Selenium/deficiency

Caesalpinia sappan L., belonging to the family Leguminosae, is a medicinal plant that is distributed in Southeast Asia. The dried heartwood of this plant is used as a traditional ingredient of food, red dyes, and folk medicines in the treatment of diarrhea, dysentery, tuberculosis, skin infections, and inflammation. Brazilin is the major active compound, which has exhibited various pharmacological effects, including anti-platelet activity, anti-hepatotoxicity, induction of immunological tolerance, and anti-inflammatory and antioxidant activities. The present study aimed to evaluate the antioxidant activity and expression of antioxidant enzymes of C. sappan L. extract and its major compound, brazilin, in human epidermal keratinocytes exposed to UVA irradiation. Our results indicated that C. sappan L. extract reduced UVA-induced HO production via GPX7 activation. Moreover, brazilin exhibited antioxidant effects that were similar to those of C. sappan L. via glutathione peroxidase 7 (GPX7), suggesting that C. sappan L. extract and its natural compound represent potential treatments for oxidative stress-induced photoaging of skin.
Antioxidants ; pharmacology ; Benzopyrans ; pharmacology ; Caesalpinia ; chemistry ; Humans ; Hydrogen Peroxide ; toxicity ; Keratinocytes ; cytology ; drug effects ; enzymology ; radiation effects ; Oxidative Stress ; drug effects ; radiation effects ; Peroxidases ; genetics ; metabolism ; Plant Extracts ; pharmacology ; Protective Agents ; pharmacology ; Ultraviolet Rays

Apoptosis is an essential factor in keeping homeostasis of the organism. Apoptosis is regulated by a series of cytokines. Bcl-2 family proteins are key regulators of apoptosis. The Bcl-2 family includes both anti- and pro-apoptotic proteins with opposing biological functions. Their interaction regulates the transmission of the apoptosis signal. High expression of anti-apoptotic members such as Bcl-2 and Bcl-xL are commonly found in human cancers. In recent years, following the disclosing of the crystal structures of Bcl-2 family proteins, researchers have paid attention to the development of the small molecule inhibitors of Bcl-2 family proteins. This article reviews the progress in this field from the view of drug design.
Antimycin A ; chemistry ; pharmacology ; Antineoplastic Agents ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Benzopyrans ; chemistry ; pharmacology ; Biphenyl Compounds ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Design ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Gossypol ; chemistry ; pharmacology ; Humans ; Nitriles ; chemistry ; pharmacology ; Nitrophenols ; chemistry ; pharmacology ; Piperazines ; chemistry ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; pharmacology ; Structure-Activity Relationship ; Sulfonamides ; chemistry ; pharmacology ; Thiazoles ; chemistry ; pharmacology ; bcl-X Protein ; antagonists & inhibitors ; pharmacology