Filiation biochimique des acides phénoliques produits parPenicillium brevi-compactum

Résumé LeP. brevi-compactum produit onze substances phénoliques différentes: l'acide mycophénolique, les acides phénoliques C₁₀H₁₀O₅, C₁₀H₁₀O₆, C₁₀H₁₀O₇ et C₈H₆O₆ et les substances phénoliques non identifiées désignées par les chiffres VI, VII, VIII, IX, X et XI. L'acide mycophénolique et les substances X et XI qui en dérivent, sont synthétisés par la moisissure suivant un processus plus complexe que les autres substances phénoliques et sans rapport direct avec lui. Ces dernières dérivent les unes des autres par une série de transformations dont certaines sont réversibles. Il semble que les substances VI et VII soient des intermédiaires entre C₁₀H₁₀O₇ et C₈H₆O₆, tandis que les substances VIII et IX seraient des produits de réduction de C₁₀H₁₀O₅.

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Summary P. brevi-compactum produces eleven phenolic different substances, mycophenolic acid, phenolic acids C₁₀H₁₀O₅, C₁₀H₁₀O₆, C₁₀H₁₀O₇ and C₈H₆O₆, and the non-identified substances designed by the numbers VI, VII, VIII, IX, X and XI. Mycophenolic acid and its derivates X and XI are synthesized by the mould according to a process more complex than the other phenolic substances and have no direct connection with them. The latter derive the one from the other, in a succession of transformations some of which are reversible. It seems that the substances VI and III are intermediaries between C₁₀H₁₀O₇ and C₈H₆O₆, the substances VIII and IX being produced by reduction of C₁₀H₁₀O₅.

     

Salivary hydrogen peroxide produced by holding or chewing green tea in the oral cavity

Tea (Camellia sinensis) catechins have been studied for disease prevention. These compounds undergo oxidation and produce H₂O₂. We have previously shown that holding tea solution or chewing tea leaves generates high salivary catechin levels. Herein, we examined the generation of H₂O₂ in the oral cavity by green tea solution or leaves. Human volunteers holding green tea solution (0.1–0.6%) developed salivary H₂O₂ with C_max = 2.9–9.6 μM and AUC_{0 → ∞} = 8.5–285.3 μM min. Chewing 2 g green tea leaves produced higher levels of H₂O₂ (C_max = 31.2 μM, AUC_{0 → ∞} = 1290.9 μM min). Salivary H₂O₂ correlated with catechin levels and with predicted levels of H₂O₂ (C_{max(expected)} = 36 μM vs C_{max(determined)} = 31.2 μM). Salivary H₂O₂ and catechin concentrations were similar to those that are biologically active in vitro. Catechin-generated H₂O₂ may, therefore, have a role in disease prevention by green tea.     

Studies on the Chlorosis-inducing Substances Produced by a Fungus

Viridominic acids A, C₃₃H₄₈O₉, B, C₃₃H₄₈O₁₀, C, C₃₃H₅₀O₉ and cephalosporin P₁ were isolated as chlorosis-inducing substances against higher plants. The isolation, physicochemical properties and biological activities of these compounds are described in detail.     

Structure Determination of Fatty Acids from Tunicamycin Complex

The structures of ten fatty acids, which were obtained by the hydrolysis of tunicamycin complex, were determined. GLC-mass, ¹H NMR and IR spectra showed that the major acids were trans-α, β-unsaturated iso acids with the formula C₁₄H₂₈O₂, C₁₆H₂₈O₂, C₁₆H₃₀O₂ and C₁₇H₃₂O₂. The minor acids were α, β-unsaturated normal acids and saturated normal and iso acids.     

Study of the Mechanism of Action of p-Chloromercuribenzoate on Endonuclease from the Bacterium Serratia marcescens

The mechanism of action of p-chloromercuribenzoate (PCMB) on Serratia marcescens nuclease was investigated. The analysis showed that PCMB forms complexes with DNA. Binding of C₇H₅O₂Hg⁺ to DNA changes the secondary structure of the DNA. These changes alter the enzymatic activity of S. marcescens nuclease, which was previously found to be sensitive to the secondary structure of the substrates. The nuclease activity was either suppressed or stimulated in the presence of PCMB depending on the C₇H₅O₂Hg⁺ to nucleotide equivalent ratio. Binding of C₇H₅O₂Hg⁺ to DNA did not form an abortive enzyme–substrate complex. Binding of Mg²⁺ to the C₇H₅O₂Hg–DNA complex caused appropriate changes in secondary structure of the substrate. Since Mg²⁺ and C₇H₅O₂Hg⁺, though differing in the type of metal cation, are similar in their mechanisms of influence on enzymatic activity of S. marcescens nuclease, the identity of other metal-containing effectors in their mechanism of action on Serratia marcescens nuclease is assumed.     

Isolation of Novel Antifungal Antibiotics,Ezomycins A1, A2, B1 and B2

From ezomycin complex produced by a strain of Streptomyces were isolated four components named ezomycins A₁ (C₂₆H₄₀N₈O₁₆S), A₂ (C₁₉H₂₈N₆O₁₃), B₁ (C₂₆H₃₉N₇O₁₇S) and B₂ (C₁₉H₂₇N₅O₁₄) which are new pyrimidine nucleosides. Ezomycins A₁ and B₁ containing l-cystathionine were found to be responsible for specific antimicrobial activity of the complex against Sclerotinia and Botrytis species.     

Studies on Polyoxins,Antifungal Antibiotics

Seven additional components, polyoxins C, D, E, F, G, H and I were isolated from polyoxin complex. They have molecular formulae corresponding to C₁₁H₁₅N₃O₈, C₁₇H₂₃N₅O₁₄, C₁₇H₂₃N₅O₁₃, C₂₃H₃₀N₆O₁₅, C₁₇H₂₅N₅O₁₂, C₂₃H₃₂N₆O₁₃ and C₁₉H₂₄N₄O₁₂, respectively. These polyoxins except inactive polyoxins C and I were highly active against various kinds of phytopathogenic fungi. The close structural similarity among them including polyoxins A and B is also discussed.     

Synthesis and preliminary biological evaluation for the anticancer activity of organochalcogen (S/se) tethered chrysin-based organometallic RuII(η6-p-cymene) complexes

Organochalcogen (S/Se) functionalized chrysin derivatives were synthesized and coordinated with Ru^II(η⁶-p-cymene) to efficiently form ruthenium-based chemotherapeutic drug entities [C₃₁H₃₅O₄SRuCl]; [C₃₁H₃₅O₄SeRuCl]; [C₃₃H₃₁O₄SRuCl]; and [C₃₃H₃₁O₄SeRuCl]. The complexes were thoroughly characterized by analytical and various spectroscopic techniques which include elemental analysis, UV–vis, IR, NMR (¹H, ¹³C, and ⁷⁷Se NMR), and HR-MS. The interaction studies of these Ru(II) complexes were carried out with CT DNA/HSA by employing UV–vis, fluorescence and circular dichroic techniques in view to examine their chemotherapeutic potential. The complexes demonstrated predominant binding toward CTDNA via electrostatic interaction while, the extent of binding was quantified by calculating intrinsic binding constant (K_b) and binding constant (K) values which revealed higher binding affinity of selenium-based chrysin complexes as compared to their thio-analogs, following the order [C₃₁H₃₅O₄SeRuCl]?>?[C₃₃H₃₁O₄SeRuCl]?>?[C₃₁H₃₅O₄SRuCl]?>?[C₃₃H₃₁O₄SRuCl]. Moreover, interaction of these complexes with human serum albumin (HSA) was also investigated which suggested spontaneous interactions of complexes with the protein by hydrogen bonding and van der Waals forces. To visualize the preferential binding sites and affinity of complexes with DNA and HSA molecular docking studies were performed. Additionally, in vitro anticancer activity of the complexes were evaluated by SRB assay on selected cancer cell lines viz., HeLa (cervical), MIA-PA-CA-2 (pancreatic), MCF-7 (breast), Hep-G2 (Hepatoma), and SK-OV-3 (ovarian) which exhibited the superior cytotoxicity of complex [C₃₁H₃₅O₄SeRuCl] as compared to other analogs on selective cancer phenotypes.

Communicated by Ramaswamy H. Sarma     

Construction of combustion models for rapeseed methyl ester bio-diesel fuel for internal combustion engine applications

Bio-diesel fuels are non-petroleum-based diesel fuels consisting of long chain alkyl esters produced by the transesterification of vegetable oils, that are intended for use (neat or blended with conventional fuels) in unmodified diesel engines. There have been few reports of studies proposing theoretical models for bio-diesel combustion simulations. In this study, we developed combustion models based on ones developed previously. We compiled the liquid fuel properties, and the existing detailed mechanism of methyl butanoate ester (MB, C₅H₁₀O₂) oxidation was supplemented by sub-mechanisms for two proposed fuel constituent components, C₇H₁₆ and C₇H₈O (and then, by mp2d, C₄H₆O₂ and propyne, C₃H₄) to represent the combustion model for rapeseed methyl ester described by the chemical formula, C₁₉H₃₄O₂ (or C₁₉H₃₆O₂). The main fuel vapor thermal properties were taken as those of methyl palmitate C₁₉H₃₆O₂ in the NASA polynomial form of the Burcat database. The special global reaction was introduced to “crack” the main fuel into its constituent components. This general reaction included 309 species and 1472 reactions, including soot and NO_x formation processes. The detailed combustion mechanism was validated using shock-tube ignition-delay data under diesel engine conditions. For constant volume and diesel engine (Volvo D12C) combustion modeling, this mechanism could be reduced to 88 species participating in 363 reactions.     

Inactivation of Bacteriophages by ε-Poly-l-lysine Produced by Streptomyces

Degradation of a β-O-4lignin substructure model dimer by a white rot fungus, Phanerochaete chrysosporium, was investigated using a culture containing H₂¹⁸O, and the following conclusions were made. a) The direct hydrolysis at C_β of the β-O-4 dimer was not involved in formation of arylglycerol. b) About half of the oxygen at the benzyl (C_α) position of the glycerol was derived from H₂O (H₂¹⁸O) and the other half was from the oxygen at the benzyl (C_α) position of the substrate β-O-4 dimer. c) But, the oxygen at the C_α position of the substrate β-O-4 dimer did not migrate to the C_α position of the aryglycerol.     

Tuber-forming Substances in Jerusalem Artichoke (Helianthus tuberosus L.)

Four tuber-forming substances in Jerusalem artichoke were isolated from the leaves. The structures were established by spectroscopic methods as jasmonic acid (2), methyl β-D-glucopyranosyl tuberonate (3), and two new polyacetylene compounds, methyl β-D-glucopyranosyl helianthenate A (4, C₁₉H₂₄O₈) and B (5, C₁₇H₂₂O₈).     

Oxidative stress impairs autophagic flux in prion protein-deficient hippocampal cells

We previously reported that autophagy is upregulated in Prnp-deficient (Prnp^0/0) hippocampal neuronal cells in comparison to cellular prion protein (PrP^C)-expressing (Prnp^+/+) control cells under conditions of serum deprivation. In this study, we determined whether a protective mechanism of PrP^C is associated with autophagy using Prnp^0/0 hippocampal neuronal cells under hydrogen peroxide (H₂O₂)-induced oxidative stress. We found that Prnp^0/0 cells were more susceptible to oxidative stress than Prnp^+/+ cells in a dose- and time-dependent manner. In addition, we observed enhanced autophagy by immunoblotting, which detected the conversion of microtubule-associated protein 1 light chain 3 β (LC3B)-I to LC3B-II, and we observed increased punctate LC3B immunostaining in H₂O₂-treated Prnp^0/0 cells compared with H₂O₂-treated control cells. Interestingly, this enhanced autophagy was due to impaired autophagic flux in the H₂O₂-treated Prnp^0/0 cells, while the H₂O₂-treated Prnp^+/+ cells showed enhanced autophagic flux. Furthermore, caspase-dependent and independent apoptosis was observed when both cell lines were exposed to H₂O₂. Moreover, the inhibition of autophagosome formation by Atg7 siRNA revealed that increased autophagic flux in Prnp^+/+ cells contributes to the prosurvival effect of autophagy against H₂O₂ cytotoxicity. Taken together, our results provide the first experimental evidence that the deficiency of PrP^C may impair autophagic flux via H₂O₂-induced oxidative stress.     

New tailored substituted benzothiazole Schiff base Cu(II)/Zn(II) antitumor drug entities: effect of substituents on DNA binding profile,antimicrobial and cytotoxic activity

New tailored Cu(II) & Zn(II) metal-based antitumor drug entities were synthesized from substituted benzothiazole o?vanillin Schiff base ligands. The complexes were thoroughly characterized by elemental analysis, spectroscopic studies {IR, ¹H & ¹³C NMR, ESI?MS, EPR} and magnetic susceptibility measurements. The structure activity relationship (SAR) studies of benzothiazole Cu(II) & Zn(II) complexes having molecular formulas [C₃₀H₂₂CuN₅O₇S₂], [C₃₀H₂₀Cl₂CuN₅O₇S₂], [C₃₀H₂₀CuF₂N₅O₇S₂], [C₃₀H₂₂N₄O₄S₂Zn], [C₃₀H₂₀Cl₂N₄O₄S₂Zn], and [C₃₀H₂₀F₂N₅O₇S₂Zn], with CT?DNA were performed by employing absorption, emission titrations, and hydrodynamic measurements. The DNA binding affinity was quantified by K _b and K _sv values which gave higher binding propensity for chloro-substituted Cu(II) [C₃₀H₂₀Cl₂CuN₅O₇S₂] complex, suggestive of groove binding mode with subtle partial intercalation. Molecular properties and drug likeness profile were assessed for the ligands and all the Lipinski’s rules were found to be obeyed. The antimicrobial potential of ligands and their Cu(II) & Zn(II) complexes were screened against some notably important pathogens viz., E. coli, S. aureus, P. aeruginosa, B. subtilis, and C. albicans. The cytotoxicity of the complexes [C₃₀H₂₀Cl₂CuN₅O₇S₂], [C₃₀H₂₀CuF₂N₅O₇S₂], [C₃₀H₂₀Cl₂N₄O₄S₂Zn], and [C₃₀H₂₀F₂N₅O₇S₂Zn] were evaluated against five human cancer cell lines viz., MCF?7 (breast), MIA?PA?CA?2 (pancreatic), HeLa (cervix) and Hep?G2 (Hepatoma) and A498 (Kidney) by SRB assay which revealed that chloro-substituted [C₃₀H₂₀Cl₂CuN₅O₇S₂] complex, exhibited pronounced specific cytotoxicity with GI₅₀ value of 4.8 μg/ml against HeLa cell line. Molecular docking studies were also performed to explore the binding modes and orientation of the complexes in the DNA helix.     

Studies on the Metabolic Products of Oospora sp.

A microorganism was isolated from the air of a patient-room and classified in the genus Oospora. This microorganism was cultured on a malt extract medium, and the mycellium was separated from the culture filtrate. A new compound (O-1), m.p. 129°C, C₁₁H₁₀O₃, and eburicoic acid, m.p. 290°C, C₃₁H₅₀O₃ were obtained from the dried mycellium. Another new compound (O-2), m.p. 176°C, C₁₁H₈O₅ was obtained from the culture filtrate.     

Studies on the Piscicidal Components of Justicia Hayatai var. decumbens

Justicidin A, C₂₂H₁₈O₇, mp 263°C and B, C₂₁H₁₆O₆, mp 240°C were isolated as fish-killing components from Justicia Hayatai var. decumbens. The piscicidal activities of both compounds were demonstrated to be as strong as rotenone and about ten times stronger than that of pentachlorophenol.     

Studies on Mitomycins,Carcinostatic Antibiotics

Mitomycin A (C₁₆H₁₉O₆N₃) and mitomycin C (C₁₅H₁₈O₅N₄) are pigments which have the quinoid structure. When treated with aqueous ammonia, mitomycin A is converted to mitomycin C. Acid hydrolysis of mitomycin C gave three degradation products, namely, C₁₄H₁₅O₅N₄, C₁₄H₁₅O₆N₃ and C₁₃H₁₄O₅N₂. Acetylation with acetic anhydride and pyridine and methylation with methyl iodide gave monoacetyl and monomethyl derivatives of mitomycin C respectively, though diacetate of demethyl derivatives were obtained when boiled with acetic anhydride.     

Multispectroscopic insight,morphological analysis and molecular docking studies of CuII-based chemotherapeutic drug entity with human serum albumin (HSA) and bovine serum albumin (BSA)

The interaction studies of Cu^II nalidixic acid–DACH chemotherapeutic drug entity, [C₃₆H₅₀N₈O₆Cu] with serum albumin proteins, viz., human serum albumin (HSA) and bovine serum albumin (BSA) employing UV–vis, fluorescence, CD, FTIR and molecular docking techniques have been carried out. Complex [C₃₆H₅₀N₈O₆Cu] demonstrated strong binding affinity towards serum albumin proteins via hydrophobic contacts with binding constants, K?=?3.18?×?10⁵ and 7.44?×?10⁴ M^–1 for HSA and BSA, respectively implicating a higher binding affinity for HSA. The thermodynamic parameters ΔG, ΔH and ΔS at different temperatures were also calculated and the interaction of complex [C₃₆H₅₀N₈O₆Cu] with HSA and BSA was found to be enthalpy and entropy favoured, nevertheless, complex [C₃₆H₅₀N₈O₆Cu] demonstrated higher binding affinity towards HSA than BSA evidenced from its higher binding constant values. Time resolved fluorescence spectroscopy (TRFS) was carried out to validate the static quenching mechanism of HSA/BSA fluorescence. The collaborative results of spectroscopic studies indicated that the microenvironment and the conformation of HSA and BSA (α–helix) were significantly perturbed upon interaction with complex [C₃₆H₅₀N₈O₆Cu]. Hirshfeld surfaces analysis and fingerprint plots revealed various intermolecular interactions viz., N–H····O, O–H····O and C–H····O linkages in a 2–dimensional framework that provide crucial information about the supramolecular architectures in the complex. Molecular docking studies were carried out to ascertain the preferential binding mode and affinity of complex [C₃₆H₅₀N₈O₆Cu] at the target site of HSA and BSA. Furthermore, only for Transmission electroscopy microscopy micrographs of HSA and BSA in presence of complex [C₃₆H₅₀N₈O₆Cu] revealed major protein morphological transitions and aggregation which validates efficient delivery of complex by serum proteins to the target site.

Communicated by Ramaswamy H. Sarma     

Studies on Polyoxins,Antifungal Antibiotics

Three strains of soil Streptomyces which belong to Streptomyces cacaoi were found to produce a new antifungal antibiotic complex, polyoxin complex. Polyoxin A and B were isolated in pure forms out of it. They are amphoteric compounds with the molecular formulas, C₂₃H₃₂N₆O₁₄ and C₁₇H₂₅N₅O₁₃ respectively. They showed very specific activities against phytopathogenic fungi.     

Flooding-induced soil and plant ethylene accumulation and water status response of field-grown tobacco

Summary Ethylene (C₂H₄) accumulation in flooded soil was related to oxygen (O₂), redox potential (Eh), and flooding rate. The water status response of tobacco (Nicotiana, tabacum L.) to these conditions was evaluated from stem diameter, relative water content, leaf water potential, and C₂H₄ content of leaf tissue. Treatments were: flooded with either 0,5, or 15 cm of water per day for 6 days. By the third day, O₂ in the soil decreased to less than 9% in treatments flooded with 5 or 15 cm of water. When O₂ in the soil air was less than 9% and redox potential (Eh) was less than +150 mv, most of the soil air samples contained some C₂H₄ and 16% contained more than 6 ppm. Very little C₂H₄ was present in soil air when O₂ exceeded 9%. Tobacco leaf C₂H₄ peaked 3 days after flooding and then declined to the preflooding level a day later, one day ahead of the rapid increase in soil C₂H₄. Wilting developed progressively beginning with the rise of C₂H₄ in the soil; leaf water potential, stem diameter, and relative leaf water content all were decreased. Soil-and plant-produced C₂H₄ are suggested as factors in reducing root permeability and increasing resistance to water uptake by tobacco.Contribution of the USDA-SEA/AR, in cooperation with the South Carolina Experiment Station.     

The Chemical Structure of the Intermediate Metabolites of Catechin I–IV

Examinations were made on two intermediate metabolites excreted after administration of (+)-catechin to the rabbit. From the infrared and ultraviolet spectra of these two substances (C₁₁H₁₂O₃ and C₁₁H₁₂O₄) and chemical properties of their various derivatives, they were identified as 3-hydroxyphenyl lactone and 3, 4-dihydroxyphenyl lactone. However, it still remains unknown whether they are δ- or γ-lactone.