Studies on plant growth-regulating substances: XXXIII. The influence of ring substituents on the plant growth-regulating activity of phenylacetic acid

A comprehensive range of phenylacetic acids substituted with nitro, halogen, methyl, amino, hydroxyl and N-acetylamino groups have been synthesized and their growth-regulating activities assessed in the wheat cylinder, pea curvature and pea segment tests. The influence of substituents on molecular shape is shown to be more important in determining activity than their effects on electron distribution. Studies with 2,6-disubstituted phenylacetic acids have indicated that the most active compounds can attain a certain spatial configuration in which one surface of the molecule, including the plane of the ring system, is flat and the carboxyl group is above with its axis of rotation perpendicular to this surface. Positional requirements for growth-regulating activity in phenylacetic acids are shown to be less important than in the phenoxyacetic and benzoic acids.     

Studies on plant growth-regulating substances

Nitrophenols structurally similar to 4-hydroxy-3-nitrobenzoic acid and 4-hydroxy-3-nitrobenzaldehyde have been examined for their ability to inhibit chloroplast development in linseed and oat seedlings, and their activity has been estimated quantitatively in specifically designed clover and Lemna bioassays. Twelve compounds were found to be active and activity is considered in relation to chemical structure. A nitro group in the 3-position and a hydroxyl group or ether linkage in the 4-position were found to be essential for activity whereas the nature of the functional group in the 1-position could vary considerably. Possibilities in which activity might arise from metabolism of the applied compound were investigated using excised wheat and pea tissue, and compounds with various groupings in the 1-position were shown to be converted to the corresponding active benzoic acid derivative.     

Studies on plant growth-regulating substances XXVIII. Halogen-substituted benzoic acids

The plant growth-regulating activities of chloro-, bromo- and iodo-isomers in 2,5-, 2,3,5- and 2,3,6-substituted benzoic acids were assessed in the wheat cylinder, pea segment and pea curvature tests. Their effects in the tomato-leaf epinasty test were also investigated. Replacing an ortho-chloro atom by bromine had little or no effect on activity. An ortho-iodo substituent, however, reduced activity in the 2,3,6-substituted series and almost completely inhibited it in the 2,5- substituted series. This decreased activity of ortho-iodo-substituted isomers is visualized as being due to a steric inhibition of the attachment of the carboxyl group to its receptor unit prior to the initiation of the growth response.     

Studies on plant growth-regulating substances XXV. The plant growth-regulating activity of cinnamic acids

Effects of ring substitution on the plant growth-regulating activities of trans- and cis-cinnamic acids have been investigated in the wheat cylinder, pea segment and pea curvature tests. Most of the cis- acids were shown to be active. Substitution of fluorine, chlorine or bromine into the ring of cis-cinnamic acid in most cases increased the activity. The results are discussed in relation to mode of action and chemical structure/biological activity relationships: 4-chlorobenzoic acid is shown to act as a competitive antagonist towards 4-chloro-cis-cinnamic acid.     

Studies on plant growth-regulating substances

The metabolism of certain 2,6-disubstituted phenols that possess high auxin activity in the pea segment, pea curvature and tomato-leaf epinasty tests, but are much less active in the wheat cylinder test, has been investigated in wheat, pea and tomato tissue. Metabolites were identified by thin-layer chromatography and a semi-quantitative assay method was developed. The low activity of 2,6-dihalogenophenols and inactivity of 2-halogeno-6-nitro-phenols and 3-halogeno-2-hydroxybenzonitriles in the wheat cylinder test was caused by rapid metabolic conversion of the compounds in this tissue to inactive compounds by a process involving hydroxylation of the aromatic ring in the para- position. No such inactivation occurred in pea and tomato tissues. Evidence for a novel detoxification of nitrophenols within both pea and wheat tissue was obtained; 2-bromo–6-nitrophenol was converted via 2-bromo-6-aminophenol to N-acetyl-2-bromo-6-aminophenol. Certain 3-halogeno-2-hydroxybenzaldehydes and corresponding aceto-phenones, although fulfilling the necessary structural and electronic criteria for auxin activity, are inactive. Metabolic studies indicate that this is because they are metabolized in wheat, pea and tomato tissues to compounds not possessing the structural requirements for auxin activity.     

Studies on plant growth-regulating substances XXVI. Isatic and anthranilic acids

The plant growth-regulating activities of isatic acid and twenty-six of its derivatives, together with the twenty-seven corresponding anthranilic acids, have been assessed in the wheat cylinder, the pea segment and the pea curvature tests. Activity was sustained by substitution in the 4- and 5-positions of isatic acid but decreased by substitution in the 3- and 6-positions. In the anthranilic acid series, the parent acid was inactive but the introduction of a large grouping (bromine or iodine) into the 5-position conferred activity. The 3,6- and 5,6-dichloro and the 3,6-dibromo acids were also active; compounds substituted in the 4-position to the carboxyl group or disubstituted in the 3,5-positions, were, as expected, inactive. In metabolism experiments on wheat and pea tissues with isatic and 5-chloroisatic acids the corresponding anthranilic acid was formed, together with an unidentified non-acidic metabolite in each case. There was no evidence that the growth regulating activity of isatic acids was related to this breakdown and it is concluded that the acids possess activity per se. The results are briefly discussed in terms of recent theories relating chemical structure to plant growth-regulating activity.     

Studies on plant growth-regulating substances. XLIII. 2 -Chloro -3 -phenoxypropionitriles

A number of ring substituted 2-chloro-3-phenoxypropionitriles have been prepared and their plant growth-regulating activity has been assessed in the wheat coleoptile, pea segment and pea curvature tests, and also by spray treatments on tomato and dwarf French bean plants. The activities of these compounds are compared with those of previously studied 2-chloro-3-phenylpropionitriles and the results are discussed in terms of chemical structure/biological activity relationships and mode of action.     

Studies on plant growth-regulating substances. XL. 2-Chloro-3-phenylpropionitriles

The complete series of chloro-, dichloro-, methyl-, dimethyl- and chloro-methyl-ring substituted 2-chloro-3-phenylpropionitriles and several related compounds have been prepared. Their auxin activities have been assessed in the wheat coleoptile, pea segment and pea curvature tests, and the results, which are discussed in relation to molecular structure, support the suggestion by other workers that the observed activity is due to rapid uptake of the nitriles by the plant tissues, followed by metabolism to the corresponding phenylacetic acid. The high growth promoting activity of 2-chloro-3-(3-chloro-2-methyl-phenyl)propionitrile (orthonil) is confirmed but 2-chloro-3-(2,3-dichloro-phenyl)propionitrile and 2-chloro-3-(2,3-dichlorophenyl)butyronitrile are shown to be the most active members of the series.     

Studies on plant growth-regulating substances. LIV. Factors affecting the production of active growth substances from structurally related amines in plants

A diamine oxidase enzyme has been isolated from pea epicotyls and purified. The in vitro rates at which a number of amines, structurally related to plant growth substances, are oxidised by this enzyme have been measured. These rates when considered together with the growth regulating activity of the acid ultimately produced, enable an assessment of the activity of the amine as a hormone-type herbicide to be made.     

Significant enhancement in radical-scavenging activity of curcuminoids conferred by acetoxy substituent at the central methylene carbon

For a compound to be a radical-trapping antioxidant, the antioxidant-derived radical must be sufficiently inert to molecular oxygen as this would generate harmful chain-propagating peroxyl radicals. Curcumin has a unique structure with phenolic hydroxyl group as well as β-diketone moiety in the same molecule, both of which are able to donate electrons to free radicals. However, due to the reactivity toward molecular oxygen, the carbon-centered radical derived from β-diketone moiety do not serve as radical-trapping antioxidants. In this study, we reasoned that stabilization of the carbon-centered radical through substitution with an electron-withdrawing group would enhance the radical-scavenging antioxidative activity of the resulting curcuminoids. Thus, various substituents (methyl, allyl, methoxy, xanthate, and acetoxy) covering broad spectrum of the polar substituent effect were introduced to the central methylene position of both phenolic and non-phenolic curcuminoids. With the free phenolic hydroxyl groups present, the methylene-substituent did not exert significant effect on the antioxidant activity of the curcuminoids (EC(50)=23.2-30.3 μM) with the exception of the acetoxy-substituted derivative (EC(50)=8.7 μM) which showed more potent activity than curcumin (EC(50)=22.6 μM). When substituted to the non-phenolic curcumin scaffold, however, the methylene-substituent enhanced antioxidant activity of the otherwise inactive curcuminoids in the increasing order of methyl相似文献   

Towards the discovery of drug-like epigallocatechin gallate analogs as Hsp90 inhibitors

(−)-Epigallocatechin gallate (EGCG) is the major flavonoid of green tea and has been widely explored for a range of biological activities including anti-infective, anti-inflammatory, anti-cancer, and neuroprotection. Existing structure–activity data for EGCG has been largely limited to exploration of simple ethers and hydroxyl deletion. EGCG has poor drug-like properties because of multiple phenolic hydroxyl moieties and a metabolically labile ester. This work reports a substantial expansion of structure–activity understanding by exploring a range of semi-synthetic and synthetic derivatives with ester replacements and variously substituted aromatic and alicyclic groups containing more drug-like substituents. Structure–activity relationships for these molecules were obtained for Hsp90 inhibition. The results indicate that amide and sulfonamide linkers are suitable ester replacements. Hydroxylated aromatic rings and the cis-stereochemistry in EGCG are not essential for Hsp90 inhibition. Selected analogs in this series are more potent than EGCG in a luciferase refolding assay for Hsp90 activity.     

Studies on plant growth-regulating substances XXIX. The plant growth-retarding properties of certain ammonium, phosphonium and sulphonium halides

Wheat, pea and dwarf bean seedlings grown under controlled environmental conditions were used to assess the growth-retardant activity of members of series of chloro-substituted benzyl-, trimethyl- and tri-n-butyl- ammonium bromides. The influence on activity of trialkyl groupings other than tri-methyl and tri-n-butyl was also studied using compounds with the 4-chloro-benzyl ring structure. 3-Chloro- and 4-chloro-benzyltributylammonium bromides were the most effective compounds. The activity was similar to that of 2,4-dichlorobenzyltributylphosphonium bromide (Phosphon-D) and they showed little phytotoxicity. A series of chlorophenoxymethyltributylammo-nium and phosphonium salts were found to have lower activity than the corresponding chlorobenzyl derivatives. Allyldimethylsulphonium bromide retarded the growth of wheat seedlings but, like the aliphatic trimethylam-monium bromides tested, it was only slightly active in the pea-seedling test. The results are considered in relation to the chemical structure of the compounds studied. In particular, the influence of chlorine substitution in the ring of benzyltributylammonium salts on their growth-retardant activity is compared with the effect of similar substitution on the auxin activity of phenoxyacetic acids.     

Design,synthesis and SAR study of hydroxychalcone inhibitors of human β-secretase (BACE1)

According to the structural characteristics of isoliquiritigenin from Glycyrrhiza uralensis, a series of hydroxychalcones has been designed, synthesized and evaluated for their in vitro inhibitory activities of β-secretase (BACE1). Structure-activity relationship study suggested that inhibitory activity against BACE1 was governed to a greater extent by the hydroxyl substituent on A- and B-ring of the chalcone, and the most active compound was substituted with four hydroxyl group (17, IC₅₀?=?0.27 μM).     

Studies on plant growth-regulating substances

The dwarfing of seedlings of Phaseolus vulgaris cv. Masterpiece by treatment with solutions of 4-chlorobenzyltributylammonium bromide (B₄) as a foliar spray or by application to the roots has been demonstrated. Dwarfing resulted from a reduction of internodal and petiolar lengths but there was no evidence of delayed leaf or flower development. A reduction in transpiration rate was accompanied by some protection against wilting and an increased ability to recover from this condition. No changes in transpiration coefficient were observed. The primary leaves of treated seedlings retained chlorophyll longer than those of control seedlings, but in other leaves, chlorophyll and carotenoid pigment levels tended to fall following treatment with B₄. Evidence was obtained that B₄ treatment delayed root nodule formation, an effect which could be associated with the antibacterial properties of quaternary ammonium salts.     

Studies on plant growth-regulating substances LIII. The conversion of certain substituted ethylamines to active growth substances in plants

A number of substituted phenylethylamines have been synthesised and their plant growth-regulating activities, in standard wheat and pea tests, have been determined and compared with those of related substituted phenoxyethylamines, phenylacetic acids and phenoxyacetic acids. The effects of applying the most active amines to various plant species are described and the results are considered in relation to the possible ability of the plant to convert the amine into the physiological active acetic acid derivative.     

Studies on plant growth-regulating substances XLV. Phenoxyacetaldehyde derivatives

Plant growth-regulating activity in a series of phenoxyacetaldehyde derivatives has been assessed in a number of tests. Metabolic experiments using labelled ¹⁴C compounds are discussed.     

The Stereodynamics of 5,5’‐Disubstituted BIPHEPs

We investigated the stereodynamics of 5,5’‐substituted tropos BIPHEP ligands (2,2’‐bis(diphenylphosphino)‐biphenyls) by enantioselective dynamic high‐performance liquid chromatography (DHPLC) to elucidate the influence of the substitution pattern and electronics of the substituents (methyl, methoxy, and hydroxyl groups). By temperature‐dependent dynamic HPLC measurements the activation parameters ΔG^╪, ΔH^╪, and ΔS^╪ could be determined with high precision, revealing that the activation barrier of these 5,5’‐substituted BIPHEP ligands ranges in a narrow band between 87.8 and 93.0 kJ mol^–1, making them highly attractive as deracemizable dynamic chiral ligands in asymmetric catalysis. Interestingly, the activation parameters are highly influenced by a hydroxyl or methoxy group in the 5,5’‐position of the BIPHEP ligands. Chirality 25:126–132, 2013. © 2012 Wiley Periodicals, Inc.     

Flavones are inhibitors of HIV-1 proteinase.

Substituted gamma-chromones were found to weakly inhibit HIV-1 proteinase, an important enzyme in the replication and processing of the AIDS virus. Chromones bearing hydroxyl substituents and a phenolic group at the 2-position (flavones) were the most active compounds and structure-activity relationships for a limited series of flavone inhibitors are presented. Dixon plots are reported and a possible mechanism for flavone-induced inhibition is proposed. The results are also compared with those for some structurally related non-peptidic inhibitors of HIV-1 proteinase. Since some flavonoid compounds have already been shown to have antiviral activity against AIDS, the present observations of anti-HIV-1 proteinase activity may be particularly significant.     

Antitumor activity of the lipid fraction of the spores of an anaerobic bacterium <Emphasis Type="Italic">Clostridium butyricum</Emphasis>

Antitumor activity of the preparation of the lipid fraction of Clostridium butyricum spore extract was demonstrated in vivo on a transplantable mouse model of breast cancer. At a specific scheme of application, inhibition of tumor growth and improved survival dynamics compared to the control group were observed. Thin-layer chromatography (TLC) of the lipid fraction of the spore extract revealed, apart from a saturated hydrocarbon, cholesterol ester, cetyl palmitate, triacyl glycerol, and palmitic acid, also a phenolic lipid bound in a complex with a peptide component. Acetone extraction of the lipid pool revealed a phenolic lipid. According to the TLC and ¹H-NMR spectrum of the acetone extract of the lipid fraction of C. butyricum spores, the structure of the phenolic lipid was proposed, n -butyl benzoate substituted in the para position. The phenolic lipid is suggested to be responsible for the biological activity of the spore’s lipid fraction.     

Specificity of 1-triacontanol as a plant growth stimulator and inhibition of its effect by other long-chain compounds

The effect of several analogs of 1-triacontanol (TRIA), differing in C-chain length (16–32), the position of the hydroxyl group and the terminal functional group, were tested alone and in combination with TRIA on the growth of rice (Oryza sativa L.), maize (Zea mays L.) and tomato (Lycopersicon esculentum Mill.) seedlings. Applied alone, none of the compounds caused an increase in growth; thus, chain length (30 C) and presence and position (terminal) of the hydroxyl group appear to be specific for the growth-promoting activity of TRIA. When applied simultaneously with TRIA, all analogs inhibited the response to the latter in all three test plants, whether applied in the nutrient solution, as foliar spray or by seed soaking. 1-Octacosanol inhibited the response of rice seedlings to 2.3 x 10^-8 M TRIA at concentrations as low as 2.4 x 10^-12 M. Thus preparations of TRIA and application equipment must be free from trace amounts of other long-chain compounds if they are to be used to increase plant growth.Abbreviation TRIA 1-triacontanol