Vitamin D and related compounds as plant growth substances

Vitamin D and related compounds (hydroxylated derivatives and glycosides) occur naturally in certain plants. The metabolism of vitamin D₃ in Solanum malacoxylon Sendtn. is similar in certain respects to that in animal systems. There is also evidence that vitamin D₃, plays a role in processes regulated by Ca²⁺ in plants. Vitamin D₃ possesses plant growth substance activities and in particular enhances adventitious root formation.     

Oleanolic acid and related derivatives as medicinally important compounds

Oleanolic acid has been isolated from chloroform extract of Olea ferruginea Royle after removal of organic bases and free acids. The literature survey revealed it to be biologically very important. In this review the biological significance of oleanolic acid and its derivatives has been discussed. The aim of this review is to update current knowledge on oleanolic acid and its natural and semisynthetic analogs, focussing on its cytotoxic, antitumer, antioxidant, anti-inflamatory, anti-HIV, acetyl cholinesterase, alpha-glucosidase, antimicrobial, hepatoprotective, anti-inflammatory, antipruritic, spasmolytic activity, anti-angiogenic, antiallergic, antiviral and immunomodulatory activities. We present in this review, for the first time, a compilation of the most relevant scientific papers and technical reports of the chemical, pre-clinical and clinical research on the properties of oleanolic acid and its derivatives.     

Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation

Until now only few data have been reported on biochemically explicable pharmacological effects of flavonoid structures. When tested against arachidonic acid metabolism many flavonoids were found to be effective against the lipoxygenase and cyclo-oxygenase pathways. Some flavonoids were predominant inhibitors of either cyclo-oxygenase or lipoxygenase, others were equally effective against both enzymes. Therefore, these compounds proved to be useful tools to elucidate fatty acid peroxidation problems.     

Halogenated epoxides and related compounds as inhibitors of epoxide hydrase

A variety of chlorinated and fluorinated epoxides and related compounds were synthesized and evaluated as inhibitors of epoxide hydrase. The compounds were tested using chicken liver microsomes and a radiometric assay based on [³H]styrene oxide, and using partially purified chicken liver microsomal epoxide hydrase and a continuous photometric assay based on p-nitrostyrene oxide, whose hydration could be monitored at 310 nm. For the 16 compounds studied both assays gave similar patterns of inhibitory activity. As expected from the relative K_m values of the two substrates, all inhibitors were considerably more active against styrene oxide (K_m =1.0 mM) than against p-nitrostyrene oxide (K_m = 4.2 μM), and styrene oxide was a weak alternate-substrate inhibitor against p-nitrostyrene oxide. 1,1,1-Trichloropropene oxide, however, was a potent alternate-substrate inhibitor against p-nitrostyrene oxide. Addition of various substituents to the α-carbon of styrene oxide generated a series of compounds whose inhibitory potency toward p-nitrostyrene oxide increased in the order H ≈ CF₃ < CH₃ < CH₂Cl < CHCl₂ < CCl₃ ≈ 1,1,1-trichloropropene oxide. In contrast, addition of a CH₃ or CCl₃ group to the β-carbon of styrene oxide resulted in only a modest increase in inhibitory potency. 2-Phenyl- and 3-phenyloxetane showed no pronounced inhibitory activity toward either styrene oxide or p-nitrostyrene oxide, but pentafluorophenyl ethylene oxide and 1,1, 1-trichlorobutane-3,4-oxide were moderately active inhibitors, although significantly less potent than 1,1,1-trichloroproene oxide. These results show that electronegativity, steric effects, and hydrophobic effects are each important in governing the interaction of epoxide hydrase substrates with the enzyme, although it is not yet possible to analyze separately the effects of each of these parameters on K_m, V, and the catalytic mechanism.     

Quinoline-3-carbothioamides and related compounds as novel immunomodulating agents

A series of quinoline-3-carbothioamides and their analogues was prepared via four synthetic routes and evaluated for their antinephritic and immunomodulating activities. The optimal compound 9g strongly inhibited the T-cell independent antibody production in mice immunized with TNP-LPS and was highly effective in two nephritis models, namely chronic graft-versus-host disease and autoimmune MRL/l mice.     

Copper complexes of 1,10-phenanthroline and related compounds as superoxide dismutase mimetics

In a preliminary study we tested CuSO4.5H2O, (Cu(II]2[3,5-diisopropylsalicylate]4.2H2O and a number of copper complexes of substituted 1,10-phenanthrolines for superoxide anion dismutase activity. It appeared that this activity depends on the ligands involved and might be governed by the redox potential of the Cu(I) complex/Cu(II) complex couple. The strong superoxide anion dismutase activity of Cu(II)[DMP]2 complex can be expected considering its high redox potential. Rather surprisingly is the superoxide anion dismutase activity of the Cu(I)[DMP]2 complex since it involves oxidation to Cu(II)[DMP]2 complex. From regression analysis it was established that steric and field effects of the substituents of the investigated phenanthrolines play an important role in SOD activity and therefore it is concluded that complex formation is important for the superoxide dismutase-like activity.     

3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).     

Structural analysis of isosteviol and related compounds as DNA polymerase and DNA topoisomerase inhibitors

Isosteviol (ent-16-ketobeyeran-19-oic acid) is a hydrolysis product of stevioside, which is a natural sweetener produced in the leaves of Stevia rebaudiana (Bertoni) Bertoni. In this report, we prepared isosteviol and related compounds from stevioside by microbial transformation and chemical conversion and assayed the inhibitory activities toward DNA metabolic enzymes and human cancer cell growth. Among twelve compounds obtained, only isosteviol (compound 3) potently inhibited both mammalian DNA polymerases (pols) and human DNA topoisomerase II (topo II), and IC50 value for pol alpha was 64.0 microM. This compound had no inhibitory effect on higher plant (cauliflower) pols, prokaryotic pols, human topo I, and DNA metabolic enzymes such as human telomerase, T7 RNA polymerase, and bovine deoxyribonuclease I. With pol alpha, isosteviol acted non-competitively with the DNA template-primer and nucleotide substrate. Isosteviol prevented the growth of human cancer cells, with LD50 values of 84-167 microM, and 500 microg of the compound caused a marked reduction in TPA (12-O-tetradecanoylphorbol-13-acetate)-induced inflammation (inhibitory effect, 53.0%). The relationship between the structure of stevioside-based compounds and these activities were discussed.     

Synthesis of prumycin and related compounds

Prumycin (1) and related compounds have been synthesized from benzyl 2-(benzyloxycarbonyl)amino-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside (4). Benzoylation of 4, followed by deisopropylidenation, gave benzyl 3-O-benzoyl-2-(benzyloxycarbonyl)amino-2-deoxy-β-d-glucofuranoside (6), which was converted, via oxidative cleavage at C-5–C-6 and subsequent reduction, into the related benzyl β-d-xylofuranoside derivative (7). Benzylation of 3-O-benzoyl-2-(benzyloxycarbonyl)-amino-2-deoxy-d-xylopyranose (8), derived from 7 by hydrolysis, afforded the corresponding derivatives (9, 11) of β- and α-d-xylopyranoside, and compound 7 as a minor product. Treatment of benzyl 3-O-benzoyl-2-(benzyloxycarbonyl)amino-2-deoxy-4-O-mesyl-β-d-xylopyranoside 10, formed by mesylation of 9, with sodium azide in N,N-dimethylformamide gave benzyl 4-azido-3-O-benzoyl-2-(benzyloxy-carbonyl)amino-2,4-dideoxy-α-l-arabinopyranoside (13), which was debenzoylated to compound 14. Selective reduction of the azide group in 14, and condensation of the 4-amine with N-[N-(benzyloxycarbonyl)-d-alaninoyloxy]succinimide, gave the corresponding derivative (15) of 1. Reductive removal of the protecting groups of 15 afforded 1. Prumycin analogs were also synthesized from compound 14. Evidence in support of the structures assigned to the new derivatives is presented.     

Mutagenicity of benzotrichloride and related compounds

Benzotrichloride (BTC), benzal chloride (BDC), benzyl chloride (BC) and benzoyl chloride (BOC) were surveyed for their mutagenicity in microbial systems such as rec-assay using Bacillus subtilis and reversion assays using E. coli WP2 and Ames Salmonella TA strains with or without metabolic activation in vitro. BTC and BDC required metabolic activation for their mutagenic activities in several strains of E. coli and Salmonella. The mutagenic metabolites of these compounds may not have been produced by hydrolysis. BC was weakly mutagenic without metabolic activation. Only BOC exhibited no mutagenic activity in the detection procedures used. The mutagenic metabolite of BTC might be very unstable under our experimental conditions. The strain E. coli WP2 try her was more sensitive than E. coli B/r WP2 try (her⁺ with regard to the mutagenicity of BTC.     

Nucleotides and related compounds in bracken

The role of sugar nucleotides in polysaccharide synthesis is discussed. The presence of acid soluble nucleotides in bracken rhizomes was demonstrated (20 μmol/kg fresh weight) and the uridine series was shown to predominate accounting for some 80% of the total. The following were identified, UDP-glucose (60%), UDP-galactose (15%), UDP-xylose (9%), UDP-arabinose (3%), UDP-glucuronic acid (4%), GDP-mannose (6%) and GDP-fucose (3%). It is probable that these sugar nucleotides supply the full complement of sugars identified in the carbohydrate fractions of bracken.     

Phenethylamine and related compounds in plants

A comprehensive and up-to-date listing is provided of the distribution of phenethylamines in the Plant Kingdom. Such a listing is of importance because of their considerable physiological activity in higher animals. Their distribution in plants is also of some taxonomic interest.     

Metabolism of camphors and related compounds

1. The metabolism of (+/-)-norcamphor, (+)-camphor, (-)-camphor, (+)-epicamphor, (+/-)-camphorquinone, (+/-)-camphane-2,5-dione and camphane was investigated in rabbits. All the compounds except camphane-2,5-dione increased the content of glucuronide in the urine. 2. (+/-)-Norcamphor was reduced to endo-norborneol; (+)-camphor, contrary to expectation, was reduced to (+)-borneol, as well as being hydroxylated to (+)-5-endo-hydroxycamphor and (+)-3-endo-hydroxycamphor, 5-endo-hydroxycamphor being the predominant product. (+)-Epicamphor was reduced mainly to (+)-epiborneol; (+/-)-camphorquinone gave 3-endo-hydroxycamphor and 2-endo-hydroxyepicamphor, the former being the major metabolite. (+/-)-Camphane-2,5-dione was reduced to 5-endo-hydroxycamphor. Camphane was hydroxylated to borneol and epiborneol, the latter predominating. 3. An explanation of these findings is given in terms of steric hindrance and thermodynamic stability. 4. The possibility was investigated that NADH was involved in the reductions.