Heterocyclic Amplifiers of Phleomycin. VI. Some Phenylpurines, Phenylpteridines, Phenylquinazolines and Related Compounds

1985 ◽  
Vol 38 (3) ◽  
pp. 467 ◽  
Author(s):  
DJ Brown ◽  
K Mori
Keyword(s):  
Side Chain ◽  
Methyl Groups ◽  
Bacterial System ◽  
Synthetic Routes ◽  
Related Compounds

Synthetic routes are described to a series of 2-, 6- and 8- phenylpurines , each with an appropriate S-or NH-linked side chain elsewhere in the molecule; to 2- and 4-phenylpteridines, each with a similar side chain and some with two additional C-methyl groups, to 2- and 4-phenylquinazolines, each equipped with an analogous side chain; and to two pyridinyl analogues of the above. Three of the above components are shown to have considerable activity as amplifiers of phleomycin -G in an in vitro bacterial system.

Effect of ketoconazole and other imidazole fungicides on testosterone biosynthesis

1984 ◽  
Vol 105 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Th. Schürmeyer ◽  
E. Nieschlag
Keyword(s):  
Oral Dose ◽  
Broad Spectrum ◽  
Comparative Studies ◽  
Leydig Cells ◽  
Side Chain ◽  
Testosterone Production ◽  
Structure Activity ◽  
Testosterone Biosynthesis ◽  
Related Compounds

Abstract. A single oral dose of 400 mg ketoconazole, a broad-spectrum antifungal drug, administered orally to 5 young men induced a drop in serum and saliva testosterone into the range of hypogonadism, while LH, FSH and prolactin levels remained unchanged. In vitro studies with mouse Leydig cells demonstrated a direct reversible inhibition of testosterone biosynthesis by ketoconazole. Comparative studies with chemically related compounds showed similar effects on testosterone production of mouse Leydig cells by isoconazole, miconazole, econazole and clotrimazole, while metronidazole and levamisole were without influence on testosterone biosynthesis. Since all tested imidazoles which suppress testosterone production have as a common feature a phenylated side chain of the imidazole molecule, this indicates a structure/activity relationship for the effects observed.

scholarly journals Structures and Biological Activities of Plant Glycosides: Cholestane Glycosides from Ornithogalum Saundersiae, O. Thyrsoides and Galtonia Candicans, and Their Cytotoxic and Antitumor Activities

2006 ◽  
Vol 1 (3) ◽  
pp. 1934578X0600100
Author(s):  
Yoshihiro Mimaki
Keyword(s):  
Anticancer Agent ◽  
Biological Activities ◽  
Leukemia Cells ◽  
Side Chain ◽  
Antitumor Activities ◽  
Structure Activity ◽  
Fractionation Procedure ◽  
Related Compounds

Systematic phytochemical screening of higher pants using a cytotoxicity-guided fractionation procedure resulted in the isolation from the bulbs of Ornithogalum saundersiae (Liliaceae) an acylated cholestane diglycoside, 17α-hydroxy-16β-[(O-(2-O-p-methoxybenzoyl-β-D-xylopyranosyl)-(1→3)-2-O-acetyl-α-L-arabinopyranosyl)oxy]cholest-5-en-22-one, tentatively named OSW-1. In vitro cytotoxic and in vivo antitumor screening of OSW-1 revealed that it is a possible candidate as a novel anticancer agent. Furthermore, more than 20 OSW-1-related compounds were isolated, not only from the bulbs of O. saundersiae, but also from those of O. thyrsoides and Galtonia candicans, which are taxonomically related to O. saundersiae. In vitro cytotoxic evaluation of all the isolated compounds and their semi-synthetic analogues allowed the structure-activity relationships of the OSW-1 derivatives to be established. In addition, these three plants were found to produce a series of novel cholestane glycosides with a new rearranged side-chain moiety, 24(23→22)abeo-cholestane, some of which showed potent cytotoxic activity against HL-60 leukemia cells.

Synthesis and Antifungal Activity of Coumarins Derivatives Against Sporothrix spp.

2018 ◽  
Vol 18 (2) ◽  
pp. 164-171 ◽  
Author(s):  
Luana da S.M. Forezi ◽  
Luana Pereira Borba-Santos ◽  
Mariana F.C. Cardoso ◽  
Vitor F. Ferreira ◽  
Sonia Rozental ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agents ◽  
Sporothrix Schenckii ◽  
Public Health Problem ◽  
Domestic Animals ◽  
Coumarin Derivatives ◽  
Sporothrix Brasiliensis ◽  
Synthetic Routes ◽  
Effective Drugs

Sporotrichosis is a serious public health problem in Brazil that affects human patients and domestic animals, mainly cats. Thus, the search for new antifungal agents is required also due to the emergence and to the lack of effective drugs available in the therapeutic arsenal. The aim of this study was to evaluate the in vitro antifungal profile of two synthetic series of coumarin derivatives against Sporothrix schenckii and Sporothrix brasiliensis. The three-components synthetic routes used for the preparation of coumarin derivatives have proved to be quite efficient and compounds 16 and 17 have been prepared in good yields. The inhibitory activity of nineteen synthetic coumarins derivatives 16a-i and 17a-j were evaluated against Sporothrix spp. yeasts and the most potent compounds were 16b and 17i. However, according to concentrations able to inhibit (minimum inhibitory concentrations) and kill (minimum fungicidal concentrations) the cells, 17i was more effective than 16b against Sporothrix spp. Thus, 17i exhibited good antifungal activity against S. brasiliensis and S. schenckii, suggesting that it is an important scaffold for the development of novel antifungal agents.

scholarly journals Acyl-CoA oxidase complexes control the chemical message produced by Caenorhabditis elegans

2015 ◽  
Vol 112 (13) ◽  
pp. 3955-3960 ◽  
Author(s):  
Xinxing Zhang ◽  
Likui Feng ◽  
Satya Chinta ◽  
Prashant Singh ◽  
Yuting Wang ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Environmental Conditions ◽  
Side Chain ◽  
Side Chains ◽  
Activity Assay ◽  
C Elegans ◽  
Substrate Preferences ◽  
Acyl Coa Oxidase ◽  
Coa Thioesters

Caenorhabditis elegans uses ascaroside pheromones to induce development of the stress-resistant dauer larval stage and to coordinate various behaviors. Peroxisomal β-oxidation cycles are required for the biosynthesis of the fatty acid-derived side chains of the ascarosides. Here we show that three acyl-CoA oxidases, which catalyze the first step in these β-oxidation cycles, form different protein homo- and heterodimers with distinct substrate preferences. Mutations in the acyl-CoA oxidase genes acox-1, -2, and -3 led to specific defects in ascaroside production. When the acyl-CoA oxidases were expressed alone or in pairs and purified, the resulting acyl-CoA oxidase homo- and heterodimers displayed different side-chain length preferences in an in vitro activity assay. Specifically, an ACOX-1 homodimer controls the production of ascarosides with side chains with nine or fewer carbons, an ACOX-1/ACOX-3 heterodimer controls the production of those with side chains with seven or fewer carbons, and an ACOX-2 homodimer controls the production of those with ω-side chains with less than five carbons. Our results support a biosynthetic model in which β-oxidation enzymes act directly on the CoA-thioesters of ascaroside biosynthetic precursors. Furthermore, we identify environmental conditions, including high temperature and low food availability, that induce the expression of acox-2 and/or acox-3 and lead to corresponding changes in ascaroside production. Thus, our work uncovers an important mechanism by which C. elegans increases the production of the most potent dauer pheromones, those with the shortest side chains, under specific environmental conditions.

scholarly journals In vitro actions of NN-dimethyl-2-aminoindane and related compounds

1980 ◽  
Vol 32 (1) ◽  
pp. 751-756
Author(s):  
HILARY J. LITTLE ◽  
J. M. H. REES
Keyword(s):  
Related Compounds

Alteration in the expression of genes for cholesterol side-chain cleavage enzyme and 21-hydroxylase by hypophysectomy and ACTH administration in the rat adrenal

1990 ◽  
Vol 4 (3) ◽  
pp. 239-245 ◽  
Author(s):  
T. Imai ◽  
H. Seo ◽  
Y. Murata ◽  
M. Ohno ◽  
Y. Satoh ◽  
...  
Keyword(s):  
Steady State ◽  
Adrenal Weight ◽  
Side Chain ◽  
Total Rna ◽  
Side Chain Cleavage ◽  
Chain Cleavage ◽  
Acth Treatment ◽  
Steady State Levels ◽  
Cytochrome P 450

ABSTRACT The changes in steady-state levels of mRNA for cholesterol side-chain cleavage cytochrome P-450 (P-450scc) and steroid 21-hydroxylase cytochrome P-450 (P-450c21) caused by hypophysectomy and ACTH treatment were determined in rat adrenals. Hypophysectomy caused marked decreases in adrenal weight and total RNA per gland. Administration of ACTH resulted in increases in adrenal weight and total RNA. A significant correlation between the amount of RNA and adrenal weight was observed. Both P-450scc and P-450c21 mRNAs were decreased by hypophysectomy and increased by ACTH treatment. P-450scc mRNA decreased to 20% and P-450c21 mRNA to 76% of control values 1 day after hypophysectomy. ACTH caused a significant increase in P-450scc mRNA after 3 h. However, a significant increase in P-450c21 mRNA was observed 12 h after administration of ACTH. These results are concordant with previous studies in vitro utilizing cultured adrenocortical cells. Moreover, the induction of steady-state levels of P-450scc mRNA was faster than that observed by other investigators in studies in vitro. These results may indicate that integrity of the adrenal gland in vivo is important for the action of ACTH.

Synthesis of Substituted -N-(5-((7-Methyl-2-Oxo-2H-Chromen-4-yl)-Methyl)-1,3,4-Thiadiazol-2-yl)-Benzamide Derivatives Using TBTU As Coupling Agent And Their Evaluation For Anti Tubercular Activity

2021 ◽  
Vol 18 ◽  
Author(s):  
Monika Kakadiya ◽  
Yunus Pasha ◽  
Malleshappa Noolvi ◽  
Ashish Patel
Keyword(s):  
Antitubercular Activity ◽  
Side Chain ◽  
Antitubercular Agents ◽  
Facile Synthesis ◽  
Aromatic Side Chain ◽  
Reaction Conditions ◽  
Coupling Reagent ◽  
H37rv Strain ◽  
Benzamide Derivatives

: Tuberculosis remains a highly infectious disease across the world. In the identification of new antitubercular agents, coumarin clubbed thiadiazole amides have been synthesized and evaluated for in vitro antitubercular activity. Due to the growing concern about chemicals and their impact on the environment, greener and faster reaction conditions needed to be incorporated. Therefore, we used TBTU as a coupling reagent for efficient and facile synthesis of substituted-N-(5-((7-methyl-2-oxo-2H-chromes-4-yl)-methyl)-1,3, 4 - thiadiazol-2-yl)-benzamide 4a-j with good yields up to 95% in mild reaction condition. All the synthesized compounds were evaluated in vitro for antitubercular activity against the H37Rv strain of M.Tuberculosis. Compounds 4c, 4f, and 4j were found active at 25 µg/mL against M. tb H37Rv. Electron withdrawing substituents present on aromatic side-chain showed promising anti-tubercular activity.

scholarly journals Design and in vitro realization of carbon-conserving photorespiration

2018 ◽  
Vol 115 (49) ◽  
pp. E11455-E11464 ◽  
Author(s):  
Devin L. Trudeau ◽  
Christian Edlich-Muth ◽  
Jan Zarzycki ◽  
Marieke Scheffen ◽  
Moshe Goldsmith ◽  
...  
Keyword(s):  
Carbon Fixation ◽  
Calvin Cycle ◽  
Computational Design ◽  
Carbon Loss ◽  
Fixation Rate ◽  
Bisphosphate Carboxylase ◽  
Stoichiometric Model ◽  
Synthetic Routes ◽  
Coa Reductase

Photorespiration recycles ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) oxygenation product, 2-phosphoglycolate, back into the Calvin Cycle. Natural photorespiration, however, limits agricultural productivity by dissipating energy and releasing CO2. Several photorespiration bypasses have been previously suggested but were limited to existing enzymes and pathways that release CO2. Here, we harness the power of enzyme and metabolic engineering to establish synthetic routes that bypass photorespiration without CO2 release. By defining specific reaction rules, we systematically identified promising routes that assimilate 2-phosphoglycolate into the Calvin Cycle without carbon loss. We further developed a kinetic–stoichiometric model that indicates that the identified synthetic shunts could potentially enhance carbon fixation rate across the physiological range of irradiation and CO2, even if most of their enzymes operate at a tenth of Rubisco’s maximal carboxylation activity. Glycolate reduction to glycolaldehyde is essential for several of the synthetic shunts but is not known to occur naturally. We, therefore, used computational design and directed evolution to establish this activity in two sequential reactions. An acetyl-CoA synthetase was engineered for higher stability and glycolyl-CoA synthesis. A propionyl-CoA reductase was engineered for higher selectivity for glycolyl-CoA and for use of NADPH over NAD+, thereby favoring reduction over oxidation. The engineered glycolate reduction module was then combined with downstream condensation and assimilation of glycolaldehyde to ribulose 1,5-bisphosphate, thus providing proof of principle for a carbon-conserving photorespiration pathway.

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