Saturated Double Bond Research Articles

Skeletal Rearrangements in the Enzyme-Catalysed Biosynthesis of Coral-Type Diterpenes from Chitinophaga pinensis.

Two diterpene synthases from the bacterium Chitinophaga pinensis were characterised. The first enzyme mainly produced the rearranged diterpene palmatol, a compound known from octocorals, while the second enzyme made the new coral-type eunicellane chitinol. The mechanisms of both enzymes were deeply studied through isotopic labelling experiments, DFT calculations, and with a substrate analog containing a saturated double bond, resulting in the formation of derailment products that gave additional insights into the nature of the cyclisation cascade intermediates. The formation of coral-type diterpenes poses interesting questions on the functions of these compounds in organisms as different as bacteria and corals.

The role of dietary fats on cognition and sarcopenia in the elderly.

To elucidate the role of dietary fats on the relationship between mild cognitive impairment and sarcopenia and help identifying and preventing the decline of cognitive and muscle function in elderly individuals. The study conducted involving a group of 1812 individuals between the ages of 61 and 92. Body composition and BMR were assessed by bioelectrical impedance analysis. Cognitive function and dietary nutrition were evaluated by neuropsychological assessments and questionnaire of food intake frequency. Lipidomics analysis was performed using UHPLC-Qtrap-MS/MS. MCI and SA are mutual influencing factors, lower intake of MUFA, PUFA and higher intake of fat was associated with cognitive dysfunction and/or SA (p < 0.05). PUFA was important for MCI combined with SA (Compared with Q1, Q4 OR: 0.176, 95%CI: 0.058,0.533). Lipidomics analysis revealed that triacylglycerol (TAG) contain more carbon chains with saturated double bonds may be closely related to cognitive impairment and the progression of SA (p < 0.05). While, DAG with carbon chains of unsaturated double bonds is opposite. Insufficient intake of unsaturated fatty acids was associated with the development of cognitive decline and the progression of SA. MUFA affecting muscle health, fats and PUFA has a greater impact on MCI combined with SA. Less MUFA intake and increasing saturated double-bonded fatty acid intake might be the key factors on promoting cognitive impairment and SA in the elderly. They have the potential to serve as prospective biomarkers indicating a higher risk of cognitive decline and/or SA in the elderly population.

Pharmacophagy in green lacewings (Neuroptera: Chrysopidae: Chrysopa spp.)?

Green lacewings (Neuroptera: Chrysopidae) are voracious predators of aphids and other small, soft-bodied insects and mites. Earlier, we identified (1R,2S,5R,8R)-iridodial from wild males of the goldeneyed lacewing, Chrysopa oculata Say, which is released from thousands of microscopic dermal glands on the abdominal sterna. Iridodial-baited traps attract C. oculata and other Chrysopa spp. males into traps, while females come to the vicinity of, but do not usually enter traps. Despite their healthy appearance and normal fertility, laboratory-reared C. oculata males do not produce iridodial. Surprisingly, goldeneyed lacewing males caught alive in iridodial-baited traps attempt to eat the lure and, in Asia, males of other Chrysopa species reportedly eat the native plant, Actinidia polygama (Siebold & Zucc.) Maxim. (Actinidiaceae) to obtain the monoterpenoid, neomatatabiol. These observations suggest that Chrysopa males must sequester exogenous natural iridoids in order to produce iridodial; we investigated this phenomenon in laboratory feeding studies. Lacewing adult males fed various monoterpenes reduced carbonyls to alcohols and saturated double bonds, but did not convert these compounds to iridodial. Only males fed the common aphid sex pheromone component, (1R,4aS,7S,7aR)-nepetalactol, produced (1R,2S,5R,8R)-iridodial. Furthermore, although C. oculata males fed the second common aphid sex pheromone component, (4aS,7S,7aR)-nepetalactone, did not produce iridodial, they did convert ∼75% of this compound to the corresponding dihydronepetalactone, and wild C. oculata males collected in early spring contained traces of this dihydronepetalactone. These findings are consistent with the hypothesis that Chrysopa males feed on oviparae (the late-season pheromone producing stage of aphids) to obtain nepetalactol as a precursor to iridodial. In the spring, however, wild C. oculata males produce less iridodial than do males collected later in the season. Therefore, we further hypothesize that Asian Chrysopa eat A. polygama to obtain iridoid precursors in order to make their pheromone, and that other iridoid-producing plants elsewhere in the world must be similarly usurped by male Chrysopa species to sequester pheromone precursors.

Structure–activity relationship of α hormones, the mating factors of phytopathogen Phytophthora

The mating hormones α1 and α2 induce sexual reproduction of the phytopathogenic genus Phytophthora. To demonstrate the structural elements responsible to hormonal activity, 17 derivatives of α1 and α2 were synthesized and their hormonal activity (oospore-inducing activity) was evaluated. The terminal ester derivatives of α1 (diacetate and dibenzoate) retained the hormonal activity, whereas a dicarbamate derivative completely suppressed the activity. Even monocarbamates showed weak activities; among them the 1-O-carbamate was less active than 16-O-carbamate, suggesting that the 1-OH group is a little more important than 16-OH. Dihydro, dehydro, and demethyl derivatives exhibited the minimum level of activity. Surviving activity of 15-epi-α1 suggested a less importance of this stereochemistry. Contrary to α1, not only the terminal diacetate derivative but also monoacetates of α2 exhibited no or little activity. Among the monoacetates, 1-O-acetyl-α2 exhibited little yet relatively better activity than the others. No activity was observed for mono- and dicarbamoyl derivatives of α2. Dihydro α2 with the saturated double bond lost most of the activity. These findings suggest that both the mating hormones α1 and α2 require most of the functional (hydroxyl, keto, and olefinic) groups they possess in their natural form for inducing the sexual reproduction of Phytophthora.

Novel Isopentenyladenosine Analogues: Synthesis, Characterization, and Evaluation of Antiproliferative Activity on Bladder Carcinoma Cells

Isopentenyladenosine (iPA), a member of the cytokinin family of plant hormones, exerts a marked antiproliferative activity on some leukemic and epithelial cancer cell lines. To characterize the molecular moieties required for the in vitro antitumor activity of the molecule and to obtain cytostatic iPA derivatives potentially useful as chemotherapeutic agents, N9-acyclic analogues have been synthesized using regioselective Mitsunobu reaction and characterized by elemental analyses, 1H and 13C NMR. These compounds were analyzed for their activity on human bladder cancer cell lines. In this study, we report that iPA inhibited the proliferation but not the migration of human bladder cancer cells, while the newly synthesized analogues revealed no significant cytostatic activity apart from the compound with a saturated double bond of the isopentenyl chain. These results indicate that the integrity of the ribose ring is required for the cytostatic activity of iPA.

Pharmacogenomics and analogues of the antitumour agent N6‐isopentenyladenosine

N(6)-isopentenyladenosine (i(6)A), a member of the cytokinin family of plant hormones, has potent in vitro antitumour activity in different types of human epithelial cancer cell lines. Gene expression profile analysis of i(6)A-treated cells revealed induction of genes (e.g., PPP1R15A, DNAJB9, DDIT3, and HBP1) involved in the negative regulation of cell cycle progression and reportedly up-regulated during cell cycle arrest in stress conditions. Of 6 i(6)A analogues synthesized, only the 1 with a saturated double bond of the isopentenyl side chain had in vitro antitumour activity, although weaker than that of i(6)A, suggesting that i(6)A biological activity is highly linked to its structure. In vivo analysis of i(6)A and the active analogue revealed no significant inhibition of cancer cell growth in mice by either reagent. Thus, although i(6)A may inhibit cell proliferation by regulating the cell cycle, further studies are needed to identify active analogues potentially useful in vivo.

Iridoid Glycosides from Globularia davisiana.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Dynamics of Energy Transfer from Lycopene to Bacteriochlorophyll in Genetically-Modified LH2 Complexes of Rhodobacter sphaeroides

LH2 complexes from Rb. sphaeroides were modified genetically so that lycopene, with 11 saturated double bonds, replaced the native carotenoids which contain 10 saturated double bonds. Tuning the S1 level of the carotenoid in LH2 in this way affected the dynamics of energy transfer within LH2, which were investigated using both steady-state and time-resolved techniques. The S1 energy of lycopene in n-hexane was determined to be approximately 12 500 +/- 150 cm(-1), by direct measurement of the S1-S2 transient absorption spectrum using a femtosecond IR-probing technique, thus placing an upper limit on the S1 energy of lycopene in the LH2 complex. Fluorescence emission and excitation spectra demonstrated that energy can be transferred from lycopene to the bacteriochlorophyll molecules within this LH2 complex. The energy-transfer dynamics within the mutant complex were compared to wild-type LH2 from Rb. sphaeroides containing the carotenoid spheroidene and from Rs. molischianum, in which lycopene is the native carotenoid. The results show that the overall efficiency for Crt --> B850 energy transfer is approximately 80% in lyco-LH2 and approximately 95% in WT-LH2 of Rb. sphaeroides. The difference in overall Crt --> BChl transfer efficiency of lyco-LH2 and WT-LH2 mainly relates to the low efficiency of the Crt S(1) --> BChl pathway for complexes containing lycopene, which was 20% in lyco-LH2. These results show that in an LH2 complex where the Crt S1 energy is sufficiently high to provide efficient spectral overlap with both B800 and B850 Q(y) states, energy transfer via the Crt S1 state occurs to both pigments. However, the introduction of lycopene into the Rb. sphaeroides LH2 complex lowers the S1 level of the carotenoid sufficiently to prevent efficient transfer of energy to the B800 Q(y) state, leaving only the Crt S1 --> B850 channel, strongly suggesting that Crt S1 --> BChl energy transfer is controlled by the relative Crt S1 and BChl Q(y) energies.

Iridoid glycosides from Globularia davisiana.

From the ethanolic extract of the aerial parts of Globularia davisiana, a new iridoid glycoside, davisioside (1), was isolated. Davisioside (1) comprises a rare iridoid aglycone structure with a saturated double bond between C-3 and C-4. Nine known iridoid glycosides, asperuloside (2), alpinoside (3), geniposide (4), globularin (5), globularicisin (6), 10-O-benzoylcatalpol (7), lytanthosalin (8), melampyroside (9), agnuside (10), and three known phenylethanoid glycosides, verbascoside, isoacteoside and leucosceptoside A were also isolated and characterized. The structures of the isolates were established by spectroscopic methods (one-dimensional (1D)- and two-dimensional (2D)-NMR, MS).

Regulation of rat hepatic 3β-hydroxysterol Δ7-reductase: substrate specificity, competitive and non-competitive inhibition, and phosphorylation/dephosphorylation

The mechanism for the catalytic reduction of the double bond at C-7, 8 in 7-dehydrocholesterol by 3beta-hydroxysterol Delta7-reductase was investigated by testing structurally related sterols as substrates and potential inhibitors. The hepatic smooth endoplasmic reticulum was identified as the site of enzyme activity. All putative substrates contained 27 carbons, but differed from 7-dehydrocholesterol by the addition of either an ethyl substituent at C-24 (7-dehydrositosterol), a double bond at C-22 with a methyl substituent at C-24 (ergosterol), epimerization of the hydroxyl from the 3beta- to 3alpha-configuration (7-dehydroepicholesterol), or a saturated double bond at C-5,6 (lathosterol). Two non-steroidal compounds that inhibit 3beta-hydroxysterol Delta7-reductase in vivo (AY 9944 and BM 15.766) were also tested. Ergosterol, 7-dehydrositosterol, and 7-dehydroepicholesterol were reduced at C-7, 8 to form brassicasterol, sitosterol, and epicholesterol, respectively, but 75% less efficiently than 7-dehydrocholesterol. Increasing concentrations of these sterols competitively inhibited 3beta-hydroxysterol Delta7-reductase activity. The double bond at C-7,8 in lathosterol was not reduced. AY 9944 and BM 15.766 inhibited 3beta-hydroxysterol Delta7-reductase activity non-competitively. 3beta-Hydroxysterol-Delta7-reductase activity declined after microsomes were exposed to alkaline phosphatase, and enzyme activity was increased by phosphorylation with Mg2+, and ATP. These results demonstrate that the reduction of the double bond at C-7,8 requires binding of the enzyme protein with the B-ring of the sterol substrate that contains a double bond at C-5,6. The reaction is hindered by substituents located on the apolar side-chain and epimerization of the hydroxyl group in ring A to a 3alpha-configuration. 3beta-Hydroxysterol Delta7-reductase exists in two forms: an active phosphorylated form and an inactive dephosphorylated form.

Characterization of synthetic retinoids with selectivity for retinoic acid or retinoid X nuclear receptors

The broad spectrum of physiological activities of retinoids is mediated by two types of receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Though they have 9- cis retinoic acid as a common ligand, the amino acid sequence of their ligand binding domains is only distantly related (27%). This fact makes it probable that the ligand binding pockets of RARs and RXRs differ significantly with respect to their three dimensional structure. Therefore, one can expect that selective ligands for these receptor subclasses do exist. A clear example of a naturally existing RAR-selective retinoid is all- trans retinoic acid. Here we report on two synthetic retinoids which are very closely related to retinoic acid in structure yet show good receptor subclass selectivity. These compounds have a saturated double bond in the polyene side chain between either the 7, 8 or 9, 10 carbon atoms and are highly RAR or RXR selective, respectively (as shown by receptor binding, transactivation activity and the ability to induce RXR homodimer formation). In addition, we present compounds of the synthetic arotinoid class which are highly RAR selective. Interestingly, the corresponding ‘9- cis analogs’ are not able to bind or activate RXR α and show greatly reduced activity on the RARs.

Substituted vitamin K epoxide analogs. New competitive inhibitors and substrates of vitamin K1 epoxide reductase

2- and 3-substituted vitamin K 2,3-epoxide analogues were synthesized and tested as inactivators, inhibitors, and substrates for beef liver microsomal vitamin K1 epoxide reductase. 2-(X)-3-phytyl-1,4-naphthoquinone 2,3-epoxides, where X is hydroxymethyl, chloromethyl, fluoromethyl, difluoromethyl, and formyl were all competitive inhibitors, but none was an inactivator. Only the 2-hydroxymethyl analogue was reduced to a quinone that was stable enough under the conditions of the experiment to be detected. Vitamin K1 epoxide analogues with modified phytyl chains (1'-hydroxy, 3'-fluoro with isomerized double bond, 1'-hydroxy and 1'-fluoro with saturated double bond, and the corresponding unsubstituted chains) were synthesized. All of the analogues were competitive inhibitors of vitamin K1 epoxide reductase. The nonfluorinated analogues also were shown to be substrates, being reduced to the corresponding quinone without enzyme inactivation. At least one other enzyme besides vitamin K1 epoxide reductase in beef liver microsomes also metabolizes all of these analogues.

The structure of the menaquinones with a tetrahydrogenated isoprenoid side-chain

Menaquinones with a tetrahydrogenated isoprenoid side-chain of Oerskovia turbata and Brevibacterium lipolyticum were cyclized to the chromenyl acetate derivatives, which were then submitted to ozonolysis, followed by reduction with dimethylsulfide. The mass-spectrometric analyses of the ozonolysis products revealed the ion peaks at m/ e 464 (M +), 449, 422, 407, 267 and 225. These results suggest that the two saturated double bonds are located continuously in the second and third units of the chain starting from the quinone ring, and the menaquinones are designated as 2-methyl-3-II,III-tetrahydromultiprenyl-1,4-naphthoquinone.

On the chemical structure of menaquinones with the tetrahydrogenated isoprenoid side chain

New menaquinones have been isolated from Oerskovia turbata and Brevibacterium lipolyticum in the nocardioform and coryneform groups of bacteria, which have been identified to be a series of menaquinones with a tetrahyhdrogenated isoprenoid chain, designated as menaquinone-9(H 4) and menaquinone-8(H 4), respectively, by thin layer chromatography, ultraviolet and infrared spectrophotometry and mass spectrometry. The nuclear magnetic resonance spectra of the quinones have revealed that all the two saturated double bonds occur in the internal units of the isoprenoid side chain.