Biomedical subjects
Publications and source records attributed to K Takeya.
Eighteen dammarane-type triterpenes were obtained from the whole plant of Cleome africana by means of cytotoxic bioassay-directed fractionation. Twelve of them were novel compounds whose structures were elucidated by various spectroscopic methods.
Two new cyclic octapeptides, dichotomin H, cyclo(-Ala-Pro-Thr-Phe-Tyr-P ro-Leu-Ile-), and dichotomin I, cyclo(-Val-Pro-Thr-Phe-Tyr-Pro-Leu-Ile-) have been isolated from the roots of Stellaria dichotoma L. var lanceolata Bge., and their structures were elucidated by extensive two-dimensional NMR methods and chemical degradation.
Four new flavonoids, luteolin 6-C-(4"-methyl-6"-O-trans-caffeoylglucoside), luteolin 6-C-(6"-O-trans-caffeoylglucoside), luteolin 6-C-(2"-O-trans-caffeoylglucoside), and luteolin 7-O-(6"-p-benzoylglucoside), together with four known ones 5, 4'-dihydroxy-3,6,7,3'-tetramethoxyflavone, luteolin, artemetin and isorhamnetin, were isolated from the root bark of Vitex agnus-castus. The structures were elucidated by spectroscopic means.
Thionation of estrogen-like active cyclic peptides, segetalins A (1) and B (2), with Lawesson's reagent provided each two thiosegetalins; thiosegetalin A1 [Gly-1-psi(CS-NH)-Val-2; Trp-5-psi (CS-NH)-Ala-6]segetalin A, thiosegetalin A2 [Gly-1-psi(CS-NH)-Val-2; Ala-6-psi(CS-NH)-Gly-1]segetalin A, thiosegetalin B1 [Gly-1-psi (CS-NH)-Val-2; Ala-3-psi(CS-NH)-Trp-4]segetalin B, and thiosegetalin B2 [Gly-1-psi(CS-NH)-Val-2; Trp-4-psi(CS-NH)-Ala-1]segetalin B. Thiosegetalin A2 only showed estrogen-like activity against ovariectomized rats. On the basis of their conformations analysed by NMR experiments, the backbone conformation was considered to play an important role in estrogen-like activity for segetalins.
Three-dimensional structures in DMSO-d0 of segetalins G [cyclo(-Gly-Val-Lys-Tyr-Ala-)] and H [cyclo(-Gly-Tyr-Arg-Phe-Ser-)], cyclic pentapeptides from seeds of Vaccaria segetalis, showing estrogen-like activity, were determined by the distance geometry calculation and restrained energy minimization from NMR data. The backbone structure of segetalin G contains one beta-turn: a beta II-like turn at Tyr4-Ala5, and that of segetalin H one beta-turn: a beta II' turn at Gly1-Tyr2 and one gamma-turn at Arg3-Phe4-Ser5 sequence. The results of distance comparison analysis proposed a pharmacophore model of estrogen-like cyclic peptides, segetalins.
Segetalins G and H (1-2) possessing estrogen-like activity are cyclic pentapeptides from the seeds of Vaccaria segetalis. Their structures, cyclo(-Gly-Ala-Lys-Tyr-Val) (1) and cyclo(-Gly-Phe-Ser-Tyr-Arg-) (2), were determined by interpretation of spectral data.
New taxoids, taxuspinanane A (1), showing potent cytotoxic activity, and taxuspinanane B (2), have been isolated from the stems of Taxus cuspidata Sieb. et. Zucc. var. nana Rehder. Their structures were elucidated by extensive 2D NMR and MS spectroscopic analysis.
Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.
A new cyclic heptapeptide, segetalin E, cyclo(-Gly-Tyr-Val-Pro-Leu-Trp-Pro-), has been isolated from the seeds of Vaccaria segetalis and the structure elucidated by extensive two-dimensional NMR methods and chemical degradation.
Four new limonoids, 1-tigloyl-3,20-diacetyl-11-methoxymeliacarpinin, 3-tigloyl-1,20-diacetyl-11-methoxymeliacarpinin, 1-cinnamoyl-3-hydroxy-11-methoxymeliacarpinin, and 1-deoxy-3-methacrylyl-11-methoxymeliacarpinin, together with a known limonoid, 1-cinnamoyl-3-acetyl-11-methoxymeliacarpinin, were isolated from the extract of the root bark of Melia azedarach. The structures were elucidated by spectroscopy.
The new anthraquinones, 6,7-dimethoxy xanthopurpurin, 6-hydroxy-7-methoxy rubiadin, 5-hydroxy-6-hydroxymethyl anthragallol 1, 3-dimethyl ether, 7-carboxy anthragallol 1,3-dimethyl ether, anthragallol 1-methyl ether 3-O-beta-D-glucopyranoside, anthragallol 1-methyl ether 3-O-rutinoside, anthragallol 3-O-rutinoside and alizarin 1-methyl ether 2-O-primeveroside were isolated from the CH2Cl2 and n-BuOH extracts of Galium sinaicum roots and their structures were established by various spectroscopic techniques. In addition, two known anthraquinones were also isolated and fully characterized.
Five new trichilin-type limonoids, named 12-deacetyltrichilin I (1), 1-acetyltrichilin H (2), 3-deacetyltrichilin H (3), 1-acetyl-3-deacetyltrichilin H (4), 1-acetyl-2-deacetyltrichilin H (5), together with four known trichilins, meliatoxin B1 (6), trichilin H (7), trichilin D (8) and 1,12-diacetyltrichilin B (9) were isolated from the extract of the root bark of Melia azedarach. The structures were elucidated by spectroscopic means and their cytotoxic activities against P388 cells in vitro were tested by means of MTT assay.
The effects of 5-(N,N-dimethyl)amiloride, a potent and specific Na(+)-H+ exchange inhibitor, were investigated in isolated perfused rabbit hearts subjected to ischemia and reperfusion. Phosphorus 31-nuclear magnetic resonance spectroscopy was used to monitor intracellular pH, creatine phosphate, beta-adenosine triphosphate, and inorganic phosphate. After cardioplegic arrest with St. Thomas' Hospital solution, normothermic (37 degrees C) global ischemia was induced for 45 minutes, and the hearts were reperfused for 50 minutes. Dimethyl amiloride at 10 mumol/L, which has minimal inotropic and chronotropic effects on the nonischemic heart, was added to the cardioplegic solution. Treatment with dimethyl amiloride reduced the elevation of left ventricular end-diastolic pressure during and after the ischemia and improved the postischemic recovery of developed pressure from 76% +/- 3.2% at 30 minutes of reperfusion in control hearts (n = 6) up to 99% +/- 1.9% in hearts treated with dimethyl amiloride (n = 8). Dimethyl amiloride did not affect the decline in intracellular pH during ischemia for up to 30 minutes but enhanced the intracellular acidosis thereafter. The intracellular pH at the end of ischemia was 6.21 +/- 0.05 in control hearts compared with 5.24 +/- 0.17 in hearts treated with dimethyl amiloride (p < 0.05). During reperfusion, intracellular pH of hearts treated with dimethyl amiloride was less than control for 5 minutes, but subsequent recovery of intracellular pH was similar to control. Treatment with dimethyl amiloride did not affect creatine phosphate breakdown, inorganic phosphate accumulation, and beta-adenosine triphosphate depletion during 45 minutes of ischemia. The creatine phosphate resynthesis and inorganic phosphate reduction during reperfusion were also unaffected. These findings suggest that Na(+)-H+ exchange plays an important role not only during reperfusion but also during ischemia for the development of postischemic cardiac dysfunction most likely by inducing primary Na+ and secondary Ca2+ overload. Specific Na(+)-H+ exchange inhibitors like dimethyl amiloride would have a potential therapeutic profile in cardiac surgery, especially if added before ischemia.
A novel cytotoxic cyclic heptapeptide, yunnanin C (1), was isolated from the roots of Stellaria yunnanensis. The structure of 1, cyclo(-Gly-Ile-Gly-Phe-Tyr-Ser-Pro-), was elucidated from spectroscopic evidence and by chemical degradation.
A 50% EtOH extract of Eucalyptus globulus leaves yielded eight phloroglucinol--sesquiterpene-coupled constituents, including three novel compounds named macrocarpals, H, I, and J. Some of these compounds possessed antibacterial activity against oral pathogenic microorganisms with MIC values ranging from 0.20 micrograms/mL to 6.25 micrograms/mL. Inhibition of glucosyltransferase activity by these compounds was also noted.
Antitumor activities on Sarcoma 180A of a series of cyclic pentapeptides, astins, isolated from the roots of Aster tataricus, were examined. The activities on various congeners of the dichlorinated proline residues prepared by chemical conversion and a hepatic microsomal biotransformation in rats suggested that 1,2-cis dichlorinated proline residues of astins A, B and C play an important role in the antitumor activity of astins.
Restrained molecular dynamics calculation in vacuo using AMBER force field implemented in MacroModel/Batchmin showed a major solution conformation in dimethyl sulfoxide-d6 of pseudostellarin D, cyclo(Gly-Tyr-Gly-Pro-Leu-Ile-Leu-). This is a cyclic heptapeptide isolated from Pseudostellaria heterophylla possessing characteristics of a beta-bulge motif with three intramolecular hydrogen bonds, two beta-turns (one type I at Pro4 and Leu5 residues, and one type II at Leu7 and Gly1 residues) and all trans amide bonds. The solution form of pseudostellarin D, which was homologous to that observed in the solid state, was also supported by Monte Carlo simulation study.
Cytosolic fura-2 Ca2+ transient signals (TCa) and the left ventricular pressure or contraction of myocardium under the positive inotropic effects of the beta-adrenoceptor agonist, isoproterenol, and the cardiac glycoside, dihydroouabain, were measured simultaneously and the results were compared. TCa was observed preceding the onset of force development and showed a steeper rise and slower decay than did the contraction curve of papillary muscle. Isoproterenol increased the steepness and the amplitude of TCa, reflecting the speed and peak force of contraction, and clearly biphasic TCa were observed with biphasic contractions developed at low frequency. Ryanodine reduced not only the early component of the contraction but also TCa, without affecting the diastolic Ca2+ level. These effects of isoproterenol were attributed to the enhanced uptake of Ca2+ by the sarcoplasmic reticulum. In contrast, dihydroouabain elevated the Ca2+ level at diastole without any change in the amplitude of TCa, suggesting that dihydroouabain inhibits the membrane Na pump thereby increasing the intracellular Ca2+ via Na(+)-Ca2+ exchange. Furthermore, a comparison of the time course of the isometric twitch curve with that of TCa in rested state contraction indicated that there are distinct differences between the mechanisms of the positive inotropic effects of isoproterenol and of dihydroouabain.