Structure-Activity Correlations with Compounds Related to Abscisic Acid

Inhibition of cell expansion of excised embryonic axes of Phaseolus vulgaris was used to evaluate the growth-inhibiting activity of abscisic acid and related compounds. None of the 13 compounds tested was as active as abscisic acid. 4-Hydroxyisophorone, a substance representative of the abscisic acid ring system was essentially inactive; cis, trans-3-methylsorbic acid, a compound resembling the side chain of abscisic acid, had low activity; and cis, trans-beta-ionylideneacetic acid was one-sixth as active. Loss of the ring double bond results in a drastic decrease in biological activity. Comparison of our results with those reported previously leads to the suggestion that the double bond of the cyclohexyl moiety may have an important function in determining the degree of activity of cis, trans-ionylideneacetic acids. Two modes of action are discussed. It seems possible that the ring double bond is involved in covalent bonding in binding of the abscisic acid analogue to macromolecules. This may require formation of an intermediate epoxide. It can also be argued that stereochemical differences between cyclohexane derivatives are important factors in determining the degree of biological activity.     

Inhibition of Zinc Metallopeptidases by Flavonoids and Related Phenolic Compounds: Structure-Activity Relationships

Abstract

Flavonoids and other benzopyrone substances, having an appropriate hydroxylation profile, may inhibit the metalloenzymes leucine aminopeptidase (LAP), aminopeptidase M (AP-M), and carboxypeptidase A (CP-A). A structural feature that evidently favours the interaction between flavonoids and the three metalloenzymes is the 2,3-double bond conjugating the A and B rings and conferring a planar structure. This can be considered virtually indispensable for inhibition of the three metallopeptidases, though the hydroxylation profile required differed for each of the enzymes, and the interaction mechanism and behaviour also differed. The inhibitory effect of flavonoids on LAP was reversible, and to be effective the flavonoid had to have conjugated A and B rings and or tho-dihydroxylation on at least one of the aromatic rings. This same requirement was essential for inhibition by coumarins and was attributed to a catechol-like mechanism of interaction. The inhibitory effects on AP-M were due to inactivation of the enzyme, irreversibly altered by flavonoids with a 2,3-double bond and a minimum of one hydroxyl substituent on each of the aromatic rings. With CP-A, conjugation of the A and B rings enhanced the inhibitory effect of flavonoids, though it was not strictly required. The interaction between the polyphenolic substances tested and the two zinc aminopeptidases was not reversed by adding zinc to the reaction medium, indicating that the inhibition is not due to the coordination of the phenolic hydroxyl groups with the catalytical zinc of active site, though the presence of zinc affected the interaction behaviour differently according to each substance's hydroxylation profile.     

茉莉酸类化合物结构与活性之间的关系及参与茉莉酸生物合成的酶

概述了茉莉酸类化合物的结构与生物活性之间的关系和参与茉莉酸生物合成的主要酶类的研究进展 ,并就这一问题的研究前景作了论述     

The Structure-Activity Relationships in Coronatine Analogs and Amino Compounds Derived from (+)-Coronafacic Acid

In order to investigate the active site of coronatine, the coronatine stereoisomers and analogs were synthesized by replacing the coronamic acid moiety with other amino compounds. The hypertrophy response of potato tubers was used for the bioassay of the compounds. A carboxyl group in coronamic acid was indispensable for the induction of activity. Moreover, the configuration at α-carbon atom in the amino acid was closely related to increase in activity Some alkyl groups of the amino acid also concerned with the activity.     

Syntheses of Thiadiazolopyrimidine and Related Compounds

A homologous transformation system was developed using the endogenous ATP-sulfurylase gene, AasC, as a selectable marker in Aspergillus aculeatus. Spontaneous mutation was proved to be beneficial in isolating AasC-deficient mutants. Molecular analysis of sC ⁺ transformants revealed that the frequency of single copy integration at ATP-sulfurylase locus was more than 40%.     

Syntheses of Paromamine and Its Related Compounds

Paromamine and its related compounds were synthesized by a modified Königs-Knorr reaction of 3,4,6-tri-O-acetyl-2-(2′,4′-dinitroanilno)-α-d-glucopyranosyl bromide with isopropylidene derivatives of 2-deoxystreptamine, streptamine and dihydroconduramine F–4. The condensed products were isolated as their poly N-acetyl derivatives and proved to have α-configuration by PMR spectroscopy in D₂O.     

Inhibitory Activities of 3-Thiophenecarboxylic Acid and Related Compounds on Plant Growth

3-Thiophenecarboxylic acid (1) showed strong growth-inhibitory activity toward the following plants but not Glycine max Merrill; Brassica campestris subsp. rapa Hook. fil. et Anders, Sesamum indicum L., Lactuca sativa L. var. longifolia Lam, Echinochloa utilis Ohwi et Yabuno and Allium tuberosum Rottler. Compound 1 strongly inhibited the growth of roots of S. indicum and L. sativa even at the low concentration of 5.0 × 10^?5 m. The growth-inhibitory activity of 1-related compounds (2–6) on S. indicum was also studied. Among the compounds, 3-thiopheneacetic acid (6) showed the strongest inhibitory activity, but 3-thiophenecarboxaldehyde (2), 3-thiophenemethanol (3), and 3-thiophenecarboxamide (5) showed no activity. The radicles of plants treated with these active compounds showed negative geotropism.     

在伤信号传导中茉莉酸与水杨酸的关系

近年来,发现茉莉酸和水杨酸都是植物体对外界伤害作出反应,表达抗性基因的信号分子。水杨酸可抑制茉莉酸类的合成及其所诱导的蛋白基因的表达;茉莉酸能阻止病原侵染后所产缮乃钏岬脑黾印＼岳蛩嵝藕抛纪揪逗退钏嵝藕抛纪揪洞嬖谧沤徊妫。牵裕薪岷蛋白和细胞分裂素可能起着信号开关的作用。     

在伤信号传导中茉莉酸与水杨酸的关系

近年来,发现茉莉酸和水杨酸都是植物体对外界伤害作出反应,表达抗性基因的信号分子。水杨酸可抑制茉莉酸类的合成及其所诱导的蛋白基因的表达;茉莉酸能阻止病原侵染后所产生的水杨酸的增加。茉莉酸信号转导途径和水杨酸信号转导途径存在着交叉,小GTP结合蛋白和细胞分裂素可能起着信号开关的作用。     

Syntheses of Naturally Occurring Terphenyls and Related Compounds

Naturally occurring terphenyls and related compounds such as terferol and its corresponding quinone and phlebiarubrone were synthesized from 2,5-diphenyl-1,4-benzoquinone. According to the proposed biosynthetic pathway, chemical conversion of phlebiarubrone to ustalic acid, a toxic compound isolated from the poisonous mushroom, Tricholoma ustale, was examined to find a low-yield conversion to the ustalic acid dimethyl ester.     

Structure-activity Relationships of Podolactones and Related Compounds

The plant-growth inhibitory activities of a number of compounds related to the podolactones were determined using a pea-stem growth system. Some conclusions regarding the effects of structure on activity are presented.     

Arginine Vasotocin: Structure-Activity Relationships and Influence on Gonadal Growth and Function

When AVT (arginine vasotocin) was given neonatally during theperiod when the brain is undergoing sexual differentiation,increased growth of the reproductive organs was observed inadulthood. Injection of AVT after this neonatal period in immatureanimals led to diminished growth of the accessory organs andin some cases the gonads themselves. The hypertrophic responseof the in situ ovary in adult mice following unilateral ovariectomy(UO) was inhibited in a dose-related manner by a single intraperitonealinjection of freshly prepared AVT. Much less AVT was requiredfor this response when injected into the third ventricle. Afterintraperitoneal injection, arginine vasopressin (AVP), lysinevasopressin (LVP), and 4-leucine vasotocin (4-leu-AVT) alsoinhibited compensatory ovarian hypertrophy whereas oxytocindid not. The commonality in die structure of these antigonadotrophicpeptides include a closed ring and a basic amino acid in position8. After opening the disulfide bond of these nonapeptides withmercaptoethanol, a single injection of the reduced AVT, AVP,LVP, or 4-leu-AVT into UO mice causes exaggerated hypertrophyof the remaining ovary. When added with leuteinizing hormone-releasinghormone (LRH) to culture medium containing hemipituitaries fromcastrated estrogen-progesterone primed female rats, AVT significantlyincreased the release of radioimmunoassayable LH above thatdue to LRH alone. AVT might interact at all levels of the hypothalamo-hypophysealgonadalaxis.     

茉莉酸对水稻侧根发生的影响

实验材料为水稻(Oryza sativa L.)栽培品种"IR8"(国际水稻所8号)及其少侧根突变体MT10.将2 d水稻幼苗种子根全部浸入0.016～50 μmol/L 茉莉酸(JA)溶液处理2 d,结果表明JA显著抑制种子根的伸长,其抑制程度与JA浓度成正比.不高于2 μmol/L的JA显著促进侧根的发生,每cm的侧根数目随浓度的增加而增加,最多可增加到原来的168%("IR8")和285%(MT10).10 μmol/L的JA仍促进处理过程中和处理后生成根区段的侧根数目的增加,但明显抑制处理前生成根区段侧根的发生,每cm的侧根数目有所下降.     

茉莉酸生物合成的调控及其信号通路

茉莉酸类化合物作为一种细胞信号分子,在植物的生长发育、机械损伤、代谢调节及诱导防御相关基因表达等方面起着重要的作用。本文概述了茉莉酸的生物合成调控以及人们目前对茉莉酸信号通路的认识,并对该研究领域存在的问题及今后可能的研究方向进行展望。     

Syntheses and Biological Activities of New Plant Growth Inhibitors Structurally Related to Abscisic Acid

Several analogs of abscisic acid (ABA) were prepared and their biological activities were assayed. Among the compounds tested, 5-(l, 2-epoxy-2, 6, 6-trimethyl-l-cyclohexyl)-, 5-(l-hydroxy-2, 6, 6-trimethyl-2-cyclohexen-l-yl)- and 5-(l-hydroxy-2-methylene-6, 6-dimethyl-l-cyclohexyl)-3-methyl-cis, trans-2, 4-pentadienoic esters (V, IX, XXIII and XXV) were found to be potent plant growth inhibitors. Their activities were superior or comparable to that of ABA.     

Halogenated Kojic Acid Derivatives,Related Compounds,and their Physiological Eflects on Plant Growth

Kojic acid has a slight stimulatory effect on plant growth as measured by the use of duckweed grown under aseptic conditions on a synthetic liquid medium. It is thought that this stimulation is due to the formation of chelatcs. This presentation is primarily concerned with the effect of various derivatives of kojic acid, particularly halogenated derivatives, on plant growth as measured by this same system. Halogenation of the 2-position results in toxic compounds. Substitution in the 6-position results in compounds with beneficial growth effects. Blockage of the 5-position causes a loss of stimulatory ability, interpreted as a loss of chelating power.     

Structure-Activity Relationships for the Antifungal Activity of Selective Estrogen Receptor Antagonists Related to Tamoxifen

Cryptococcosis is one of the most important invasive fungal infections and is a significant contributor to the mortality associated with HIV/AIDS. As part of our program to repurpose molecules related to the selective estrogen receptor modulator (SERM) tamoxifen as anti-cryptococcal agents, we have explored the structure-activity relationships of a set of structurally diverse SERMs and tamoxifen derivatives. Our data provide the first insights into the structural requirements for the antifungal activity of this scaffold. Three key molecular characteristics affecting anti-cryptococcal activity emerged from our studies: 1) the presence of an alkylamino group tethered to one of the aromatic rings of the triphenylethylene core; 2) an appropriately sized aliphatic substituent at the 2 position of the ethylene moiety; and 3) electronegative substituents on the aromatic rings modestly improved activity. Using a cell-based assay of calmodulin antagonism, we found that the anti-cryptococcal activity of the scaffold correlates with calmodulin inhibition. Finally, we developed a homology model of C. neoformans calmodulin and used it to rationalize the structural basis for the activity of these molecules. Taken together, these data and models provide a basis for the further optimization of this promising anti-cryptococcal scaffold.     

Gene-Expression Patterns and Levels of Jasmonic Acid in Rice Treated with the Resistance Inducer 2,6-Dichloroisonicotinic Acid

Acquired disease resistance can be induced in rice (Oryza sativa) by a number of synthetic or natural compounds, but the molecular mechanisms behind the phenomenon are poorly understood. One of the synthetic inducers of resistance, 2,6-dichloroisonicotinic acid (INA), efficiently protected rice leaves from infection by the rice blast fungus Magnaporthe grisea (Hebert) Barr. A comparison of gene-expression patterns in plants treated with INA versus plants inoculated with the compatible pathogen M. grisea or the incompatible pathogen Pseudomonas syringae pv syringae revealed only a marginal overlap: 6 gene products, including pathogenesis-related proteins (PR1-PR9), accumulated in both INA-treated and pathogen-attacked leaves, whereas 26 other gene products accumulated only in INA-treated or only in pathogen-attacked leaves. Lipoxygenase enzyme activity and levels of nonconjugated jasmonic acid (JA) were enhanced in leaves of plants treated with a high dose of INA (100 ppm). Exogenously applied JA enhanced the gene induction and plant protection caused by lower doses of INA (0.1 to 10 ppm) that by themselves did not give rise to enhanced levels of endogenous (-)-JA. These data suggest that INA, aside from activating a pathogen-induced signaling pathway, also induces events that are not related to pathogenesis. JA acts as an enhancer of both types of INA-induced reactions in rice.