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Biomedical subjects

S X Peng

Publications and source records attributed to S X Peng.

At least 37 records · Page 2Linked to original sources
PubMed1998

Permeability of articular cartilage to matrix metalloprotease inhibitors.

PURPOSE: To develop an in vitro cartilage permeation model for cartilage permeability study and to evaluate the effects of molecular hydrophilicity and cartilage location on the permeability of articular cartilage to matrix metalloprotease inhibitors. METHODS: An in vitro cartilage permeation model was developed and utilized to determine the permeability of articular cartilage to the matrix metalloprotease inhibitors of different hydrophilicity. Permeability coefficients were obtained by measuring the steady-state flux of the inhibitor compounds. HPLC methods were also developed and employed for the analysis of drug levels in assay media. RESULTS: The relationship between permeability and hydrophilicity of drug molecules was examined. Results indicated that the permeability coefficient increased with increasing hydrophilicity of the molecule. Additionally, the relationship between the permeability and the location of the cartilage section within the animal joint was investigated. Our results showed that the drug molecules penetrated faster in the surface layer cartilage than in the deep layer cartilage. CONCLUSIONS: Increasing the hydrophilicity of a molecule would increase its permeability across articular cartilage. The in vitro cartilage permeation model developed could be used to rank order drug compounds according to their cartilage permeability profiles and to aid in drug selection and development.

Animals↗
PubMed1997

[Synthesis and bioactivity of some 3,4-diacyloxybenzopyrans].

Considerable attention is now being given to the potassium channel openers of benzopyrans as potential therapeutical agents for hypertension. In order to search for novel antihypertensive with high efficacy and low toxicity, integrating structural features of cromakalim and praeruptorin C, twenty-four compounds of 3,4-diacyloxybenzopyrans were designed and synthesized. Some of them exhibited hypotensive activity in Sprague Dawley rats.

Animals↗
PubMed1997

[Synthesis and antiarrhythmic activity of some (erythro)-phenylpropanediolamine compounds].

For the purpose of searching for new drug with high potency and simple chemical structure, the dominant conformation and structural parameters of Guan-Fu base (GFA) molecule were modelled and calculated with a SGI-4D 25G computer. The propanediolamine chain in GFA might be considered to be a pharmacophore responsible for the bioactivity and the configuration of the chain seemed important. Thus, thirteen compounds of (erythro)-p-x-PhCHOHCHOHCH2NHR(x = H, I1-7; X = NO2, II1-6) were prepared. Among them, 10 compounds showed antiarrhythmic effect on aconitine-induced arrhythmia in rats. The ED50(to stop VT) of I2 and ED50(to stop VP) of I3 were shown to be comparable with those of GFA. In the synthesis, no stereoselectivity was found in the Prevost reaction with allylamine analogues (a1-7). After a1-7 were acetylated, the erythro type products(I1-7) were obtained.

Aconitine↗
PubMed1994

[Synthesis and biological activity of substituted benzyl/naphthylmethylisoquinolines and related quaternary ammonium derivatives].

In an attempt to search for novel antihypertensive or antiarrhythmic agents, especially compounds mainly acting on calcium or potassium channels, with the isoquinoline alkaloids which possessed cardiovascular effects as lead compounds, and on the basis of previous works of our laboratory as well as integration of the structural feature of certain potassium channel blockers, 28 compounds (I1-6 and II1-22) were designed and synthesized among which 24 were not reported previously. 3,4-Dihydroisoquinolines were first synthesized by the Bischler-Napieralski cyclization with 3,4-disubstituted phenethylamine and aromatic acetic acid as starting materials. N-alkyl substituted tetrahydroisoquinolines were prepared by the alkylation of tetrahydroisoquinolines with corresponding substituted benzyl halides, or by the reduction of dihydroisoquinoline quaternary ammonium derivatives. Preliminary pharmacological studies in vivo showed that most of these compounds exhibited various degrees of hypotensive and bradycardial effects except I4 which exhibited hypertensive activity. The hypotensive effect of II1 was the most potent among these compounds in anaesthetized normotensive Sprague-Dawley rats. Analysis of the QSAR between hypotensive/bradycardial activities of certain compounds and their structural parameters of molecular mechanics (MM2) showed that the hypotension/bradycardia increased with the increase/decrease of the charge of the nitrogen atom in the isoquinoline nucleus. Thus, the charge of the nitrogen atom might be one of the important factors which could enhance the selectivity of the compounds acting on blood vessels or cardiac tissues.

Animals↗
PubMed1993

[Traumatic lens dislocation-related glaucoma].

Among 106 patients of traumatic lens dislocation, comprising 70 males and 36 females aged 3-90 years, secondary glaucoma occurred in 93 cases (87.7%). The authors are of the opinion that lenses dislocated into the anterior chamber should be removed as soon as possible, and dislocated lens in the vitreous cavity without adhesion to the retina should also be extracted with vitrectomy. For patients with pupil block glaucoma that indicate peripheral iridectomy, the locations of operation should be carefully selected.

Adolescent↗
PubMed1993

[Structural congeners of guanfu base A and their antiarrhythmic activity].

Guanfu base A (GFA) is an alkaloid isolated from the root of Aconitum coreanum and is effective in several experimental arrhythmia models. GFA can effectively antagonize aconitine-induced arrhythmia, significantly reduce CaCl2-induced incidence of ventricular fibrillation in rats and markedly raise the ventricular fibrillation threshold to electrical stimulation in rabbits and cats. It would be valuable in clinic to treat ventricular fibrillation. Thus, we chose GFA as lead compound for chemical modification. From the view point of stereochemistry, GFA is a rigid structure and can be considered as composed of two layers. The first layer is a hydrogenated phenanthrene ring; the second is the alkylamino chain containing hydroxy and acetoxy groups [formula: see text]. It was speculated that the skeleton of such chain might play as pharmacophore contributing to the biological activity. In order to reduce the size of the molecule and simplify the chemical structure of GFA, the hydrogenated phenanthrene was removed and an aryl residue commonly occurred in the structure of antiarrhythmic agents was introduced. Thus, fourteen derivatives of phenylpropanediolamine were designed and synthesized. There is a hydrogenated indolizine ring in the structure of GFA and a indolizine ring in the structure of class III antiarrhythmic agent--butoprizine. By combing the structural feature of GFA with that of butoprizine, nine indolizine derivatives were also designed and synthesized. Screening test of 23 compounds indicated that phenylpropanediolamine derivatives--I1, I2, I3, I7, I8, I14, and indolizine derivatives--II2 markedly antagonized chloroform-induced arrhythmias in rats. Among them I2, I3, I7 and I8, appeared to be more potent than GFA.

Alkaloids↗
PubMed1992

Cardiovascular effects of substituted tetrahydroisoquinolines in rats.

1. A series of substituted tetrahydroisoquinolins derived from the cleavage products of tetrandrine were found to inhibit [3H]-nitrendipine binding to rat cerebral cortical membranes. Those compounds which displaced [3H]-nitrendipine binding were also able to inhibit high KCl-induced contraction of rat aorta in vitro. 2. There was a significant correlation between the ability of these tetrahydroisoquinolines to inhibit [3H]-nitrendipine binding and KCl-induced contraction (r = 0.99, P less than 0.001). 3. CPU-23 (1-(1-[(6-methoxy)-naphth-2-yl])-propyl-2-(1-piperidine)-acetyl- 6,7- dimethoxy-1,2,3,4-tetrahydroisoquinoline), one of the most potent compounds identified in this series, behaved as a simple competitive inhibitor at the [3H]-nitrendipine binding site and reduced the apparent affinity but not the maximal number of binding sites in saturation analysis. 4. In contrast to nifedipine which caused hypotension and tachycardia, CPU-23 induced both hypotension and bradycardia in a dose-dependent manner in pentobarbitone-anaesthetized Sprague-Dawley rats, spontaneously hypertensive and age-matched normotensive WKY rats. 5. It is suggested that CPU-23 may exert its cardiovascular effects via interaction with the dihydropyridine binding site on the L-type calcium channel.

Alkaloids↗
PubMed1992

[Synthesis and biological activity of some Val(Ala)-Tyr and Val-Tyr-Tyr peptides].

15B2 and WF-10129, reported as potent angiotensin-converting enzyme inhibitors (ACEI), were used as lead compounds for design of novel ACEI. Some of Val-Tyr-Tyr and Val-Tyr peptides were synthesized and tested for ability to inhibit ACE in vitro and in Vivo. The most potent compound was found to be N-(1-benzoyl-1-carboxymethyl)-L-Alanyl-L-Tyrosine (II5, IC50 = 7.9 x 10(-10) mol/L) which was prepared by the addition of Ala-Tyr to benzoyl-acrylic acid in the presence of triethylamine. The structure-activity relationships were also discussed.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1992

[The anterior chamber depth after trabeculectomy].

The anterior chamber depth was measured with the Haag-Streit Pachymeter in 26 cases (33 eyes) of primary angle-closure glaucoma preoperatively and postoperatively on days 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 30, 45 and 60. After successful trabeculectomy, the anterior chamber depth became shallower, particularly on days 2 to 4 postoperative, and then gradually deepened after day 5. By day 14 after surgery, the anterior chamber depth was recovered up to 91% of the preoperative level, and by day 30 up to 93%, to remain essentially stable thereafter.

Aged↗
PubMed1992

[Synthesis of molluscacidal synergists].

Chemical molluscicides are useful in schistosomiasis control. A synergist can potentiate the efficacy and reduce the dosage of a molluscicide, thus decreasing the toxicity and environmental pollution. In order to search for potential molluscicidal synergists, 13 compounds of O,O-dialkyl-O-(2-substituted-3-benzofurylacetonitrile-alpha-oxi mino)phosphate or thiophosphate (VI1-13) and 2 compounds of O,O-dialkyl-O-(2-thienylacetonitrile-alpha-oximino)phosphate (X14,15) were prepared. Preliminary test demonstrated that compound X15 had strong synergic effect with sodium pentachlorophenol in combating mollusks. Compounds X14 and VI1,2,3,6,8,10,12,13, also showed some molluscicidal synergistic activity.

Animals↗
PubMed1992

[Rejection of physico-chemical indices for pathological matrix in a quantitative drug design].

In a quantitative drug design, correlation of coefficient matrix of physico-chemical indices Xi is often pathological when these indices are highly correlated. The regression equation of biological activity Y about these indices Xi obtained in this case is not stable. In this paper, a method is given to obtain a stable regression equation: giving a critical valne alpha and finding out the indices among which correlation coefficient is not less than alpha. The following are the rules to reject some of them. If Xi and Xj is highly correlated (magnitude of rij greater than or equal to alpha, rij is the correlation coefficient of Xi and Xj), and magnitude of rin greater than magnitude of rjn (rin and rjn are correlation coefficients of Xi and Xj about Y, respectively), than the index Xj is rejected, otherwise, Xi is rejected. Stable equation can be obtained by stepwise regression with the remaining indices.

Drug Design↗
PubMed1991

Anti-arrhythmic activities of six indole derivatives of changrolin.

The indole-derived compounds, which possessed side chains resembling those of changrolin (4-[3',5'-bis[(N-pyrrolidinyl)methyl]-4'-hydroxyaniline]-quinazoline) showed potent anti-arrhythmic activity by restoration of sinus rhythm from ouabain-induced tachycardia in guinea pigs. The potency was assessed by comparison of the maintenance time of sinus rhythm recovered from tachyarrhythmias induced by ouabain. The promising compound was MI2 with piperidyl residue on position 3 & 5 of phenol moiety. There was no difference in anti-arrhythmic activities resulting from substitutions between a benzene ring and methyl residue at position 2 of indole, but the latter had weaker parasympatholytic activity. The anti-arrhythmic activity of MI2 (greater than 60 min) was 2.4 times more potent then changrolin (25 min), but its anti-cholinergic activity was only half of the latter. To compare the suppressive effect on reperfusion-induced arrhythmias by iv MI2 at different time in relation to the ligation-reperfusion protocol, it was the most effective when administered either 30 min prior to coronary occlusion or at the moment of reperfusion. The compound MI might belong to the Ic group shown by the slowing impulse conduction within the heart.

Animals↗
PubMed1990

[The synthesis and biological activity of substituted tetrahydroisoquinoline compounds].

Tetrandrine possesses calcium antagonistic and hypotensive effects. It was cleaved into two compounds O-methylcoclaurine (I) and N-methylarmepavine (II) by Na/NH3. Pharmacological test indicated that I and II showed weaker calcium antagonistic activity but having alpha-adrenoceptor antagonistic effect. With I and II as lead compounds as well as integration of some structural feature of calcium antagonists and SAR of antiarrhythmic drugs, two kinds of substituted tetrahydroisoquinoline derivatives III, IV were designed and synthesized in order to search for novel cardiovascular drugs. Tetrahydroisoquinoline compounds were first synthesized by the Bischler-Napiraski cyclization with substituted phenethylamine and aromatic acetic acid or substituted cinnamic acid as starting materials. N-alkylsubstituted tetrahydroisoquinoline compounds were prepared by the reaction of 4 with alkyl halide to produce 5, then reduction of 5 by KBH4 to give III13-25. The synthesis of N-alkylaminoethyl substituted tetrahydroisoquinoline compounds involved the reaction of 6 with chloroacetyl chloride to obtain IV1-3, the reaction of IV1-3 with secondary amine to produce 9, and then reduction of 9 with LiA1H4 to give IV16-19. Preliminary tests showed that most of these compounds exhibited varied degree of alpha-adrenoceptor antagonistic effect, and some of them possess calcium antagonistic activity. In anesthetic normal rats III15, 19 showed certain degree of hypotensive effect. IV10, 11 exhibited significant protective effect on experimental arrhythmic animals. The results of quantum chemical calculation of some compounds demonstrate that the compounds might act with alpha 1-adrenoceptor by forming charge-transfer complex.

Adrenergic alpha-Antagonists↗
PubMed1990

[Hypotensive effect of naphthylmethyl isoquinoline].

Naphthylmethyl isoquinoline (NI), a modified structure of tetrandrine, was synthesized by the China Pharmaceutical University. The effects of NI on blood pressure of animals and its possible mechanism were studied. In anesthetized rats and cats, iv NI lowered the mean arterial pressure. Meanwhile, the total peripheral vascular resistance was reduced markedly, but the heart rate, cardiac output and cardiac index showed no noticeable change. In rats its hypotensive effect was stronger than tetrandrine when equal toxic doses were compared. In conscious normotensive rats, renal hypertensive rats and SHR, oral administration of this compound resulted in a marked fall of systolic blood pressure which remained at a steady low level. It decreased the pressor response of adrenaline in rats. Intra-arterial injection of NI into the perfusing system decreased the posterior limb and renal vascular resistance immediately in constant-rate perfusion of the posterior limb and renal blood vessel of rats. It shifted the cumulative dose-response curves of noradrenaline, KCl and CaCl2 to the right in isolated rabbit aortic rings and depressed their maximal responses with IC50 9.7, 7.2 and 1.6 mumol/L, respectively, which were 2.9, 9.1 and 1.8 times stronger than that of tetrandrine, correspondingly. These results suggest that the hypotensive effect of naphthylmethyl isoquinoline is mainly attributable to its arteriolar dilatation by inhibiting calcium influx.

Animals↗
PubMed1990

[Synthesis of 2-formyl (acetyl) substituted quinoline thiosemicarbazones].

A series of 2-formyl (acetyl) substituted quinoline thiosemicarbazones (III, XII, XIII) were prepared in order to evaluate their antimalarial activity. Oxidation of substituted quinolines (IV) with selenium dioxide gave 2-formyl substituted quinolines (V). 2-Acetyl substituted quinoline (IX) was obtained from IV by oxidation, esterification, Claisen condensation and decarboxylation. III1-9 were synthesized by two methods; one was by condensation of 2-formyl (acetyl) substituted quinolines with methyl hydrazinecarbodithioat to form methyl-3-[1-(2-quinolinyl)-alkylidene] hydrazinecarbodithioate (XI), then the S-methyl group of XI was displaced by substituted amines to form the desired substituted thiosemicarbazones. The other was by condensation of 2-formyl (acetyl) substituted quinolines with 4-substituted-3-thiosemicarbazide (X) to afford directly III1-9, III10-12 were obtained by selective reduction of corresponding nitro compounds with stannous chloride and XII as a by-product was obtained by the nonselective reduction of III7 with stannous chloride. 3-Hexyl-4-oxothiazolin-2-yl(2-formyl or acetyl substituted quinoline) hydrazones (XIII1,2) were prepared from III1,4 via cyclization under sodium acetate condition. Eighteen compounds were found to be inactive in mice infected with ANKA strain of Plasmodium berghei.

Animals↗