Potential antidiarrheal agents: 1-(11-Cyano-6,11-dihydrodibenzo[b,e]thiepin-11-yl-alkyl)- and 1-(10-cyano-10,11-dihydrodibenzo[b,f]thiepin-10-yl-alkyl)-4-substituted piperidines

1985 ◽  
Vol 50 (5) ◽  
pp. 1089-1096 ◽  
Author(s):  
Karel Šindelář ◽  
Jan Metyš ◽  
Miroslav Protiva
Keyword(s):  
Inhibitory Effect ◽  
Substitution Reactions ◽  
Significant Inhibitory Effect

Substitution reactions of 11-(2-bromoethyl)- and 11-(3-bromopropyl)-6,11-dihydrodibenzo[b,e]thiepin-11-carbonitrile and further of 10-(2-bromoethyl)- and 10-(3-bromopropyl)-10,11-dihydrodibenzo[b,f]thiepin-10-carbonitrile with ethyl 4-phenylpiperidine-4-carboxylate, 4-phenylpiperidin-4-ol, 4-(2-tolyl)piperidin-4-ol, 4-(4-fluorophenyl)piperidin-4-ol, 4-(2-oxobenzimidazolin-1-yl)-piperidine and 1-phenyl-1,3,8-triazaspiro[4,5]decan-4-one afforded the tricyclic piperidinoalkyl nitriles IV-XIII which are cyclic analogues of the antidiarrheal agents diphenoxylate (I) and loperamide (III). Out of the compounds prepared only IV and XI showed a significant inhibitory effect towards diarrhea elicited by intravenously administered serotonin in mice.

scholarly journals A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Ying Liu ◽  
Wenjie Liu ◽  
Ziqiang Yu ◽  
Yan Zhang ◽  
Yinghua Li ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoporosis Treatment ◽  
Inhibitory Effect ◽  
Specific Gene ◽  
Actin Ring ◽  
Treatment Target ◽  
Significant Inhibitory Effect ◽  
Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

scholarly journals Synthesis and Evaluation of Biological Activity of New Arylphosphoramidates

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Amal Thebti ◽  
M. A. K. Sanhoury ◽  
H-I. Ouzari ◽  
T. Barhoumi-slimi
Keyword(s):  
Biological Activity ◽  
Ir Spectroscopy ◽  
Acetylcholinesterase Activity ◽  
Inhibitory Effect ◽  
Bacterial Strains ◽  
Significant Inhibitory Effect ◽  
Subsequent Addition

The synthesis of new substituted arylphosphoramidates is performed in two steps through phosphorylation of the corresponding alcohols followed by aminolysis. The formation of the desired phosphoramidates depends on the subsequent addition of the two alcohols with the amine being added at the last step. The products were obtained in 58–95% yields. They were characterized mainly by multinuclear (1H, 13C, 31P, and 19F) NMR and IR spectroscopy. In addition, the antimicrobial and antiacetylcholinesterase activities were evaluated. The results showed acetylcholinesterase activity by some compounds, whilst no significant inhibitory effect against the tested bacterial strains has been recorded.

scholarly journals Effects of fragrance compounds on growth of the silkworm Bombyx mori

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11620
Author(s):  
Zhen-peng Kai ◽  
Yanwei Qiu ◽  
Xue-wei Zhang ◽  
Shan-shan Chen
Keyword(s):  
Bombyx Mori ◽  
Endocrine System ◽  
Inhibitory Effect ◽  
Ethyl Vanillin ◽  
Abnormal Growth ◽  
Significant Inhibitory Effect ◽  
Ecological Problems ◽  
Musk Xylene ◽  
Fragrance Compounds

Due to the contamination and biological toxicity of some fragrance compounds, the environmental and ecological problems of such compounds have attracted more and more attention. However, studies of the toxicity of fragrance compounds for insects have been limited. The toxicity of 48 fragrance compounds for the silkworm Bombyx mori were investigated in this study. All of the fragrance compounds examined had no acute toxicity for B. mori larvae, but eight of them (menthol, maltol, musk xylene, musk tibeten, dibutyl sulfide, nerolidol, ethyl vanillin, and α-amylcinnamaldehyde) exhibited chronic and lethal toxicity with LC50 values from 20 to 120 µM. In a long-term feeding study, musk tibeten, nerolidol, and musk xylene showed significant growth regulatory activity. They were also extremely harmful to the cocooning of B. mori, resulting in small, thin, and loose cocoons. Two important insect hormones, namely, juvenile hormone (JH) and 20-hydroxyecdysone (20-E), were quantified in hemolymph following chronic exposure to musk tibeten, nerolidol, and musk xylene, respectively. Musk tibeten significantly increased JH titer and decreased the 20-E titer in hemolymph, and musk xylene had a significant inhibitory effect on JH titer and increased 20-E titer. Although nerolidol had no effect on hormone levels, exogenous JH mimic nerolidol increased the physiological effects of JH and significantly slowed the growth rate of B. mori larvae. The results showed that these fragrance compounds could interfere with the insect endocrine system, leading to death and abnormal growth. The risk to insects of residual fragrance compounds in the environment is worthy of attention.

scholarly journals Using Lactobacillus as Probiotic to Inhibit Growth and Adhesion of Proteus mirabilis Causing Urinary Tract Infection

2008 ◽  
Vol 2 (1) ◽  
pp. 19-32
Author(s):  
Ghydaa H. A al-jeboury ◽  
Abdul Wahed Baker
Keyword(s):  
Urinary Tract Infection ◽  
Lactic Acid ◽  
Urinary Tract ◽  
Epithelial Cell ◽  
Tract Infection ◽  
Proteus Mirabilis ◽  
Inhibitory Effect ◽  
Adhesion Property ◽  
Significant Inhibitory Effect ◽  
Urine Specimens

The aim of the study was to use lactic acid bacteria (LAB), as probiotic, to treat growth and adhesion property of Proteus mirabilis isolated from patients suffering from urinary tract infection (UTI). For this purpose, one P. mirabilis isolate (P.M.9) was selected out of 9 isolates obtained from 150 urine specimens. Due to its resistance to 11 antibiotics tested, this isolate was treated with three-fold concentrated filtrates of two lactobacillus isolates (as probiotic). Results after treatment, showed that the filtrates exhibited significant inhibitory effect against the pathogenic P.M.9 and its adhesion property especially when only an average of 3-10 bacteria /cell were adhered to each epithelial cell compared to 44-55 bacteria/cell.

Isoflavones from Camphorosma lessingii Inhibit the Organic Anion Transporters OAT1 and OAT3

Planta Medica ◽  
2018 ◽  
Vol 85 (03) ◽  
pp. 225-230 ◽  
Author(s):  
Xinhui Wang ◽  
Dujuan Wang ◽  
Xue Wang ◽  
Manana Khutsishvili ◽  
Kamilla Tamanyan ◽  
...  
Keyword(s):  
Organic Anion ◽  
Inhibitory Effect ◽  
Spectroscopic Methods ◽  
Organic Anion Transporters ◽  
One Dimensional ◽  
Anion Transporters ◽  
Significant Inhibitory Effect ◽  
Phytochemical Investigation ◽  
The Family ◽  
First Time

AbstractPhytochemical investigation of Camphorosma lessingii has resulted in the isolation of four previously unreported isoflavones (1–4) and eight known compounds (5–12). Nine of these compounds (1–6, 8–10) are reported for the first time from members of the family Amaranthaceae. The structures of all isolated compounds were determined by spectroscopic methods, primarily one-dimensional and two-dimensional nuclear magnetic resonance and mass spectrometry. The absolute configuration of 6 was confirmed by circular dichroism. Inhibition of the organic anion transporters, OAT1 and OAT3, by the isolated compounds was evaluated. Among them, 7, 2′-dihydroxy- 6,8-dimethoxyisoflavone (1), 2′-hydroxy-6,7,8-trimethoxyisoflavone (2), 6,2′-dihydroxy-7,8-dimethoxyisoflavone (3), and 7-methoxyflavone (5) showed a significant inhibitory effect on 6-carboxyfluorescein uptake mediated by OAT1 and OAT3.

Panaxynol attenuates CUMS-induced anxiety and depressive-like behaviors via regulating neurotransmitters, synapses and the HPA axis in mice

2020 ◽  
Vol 11 (2) ◽  
pp. 1235-1244 ◽  
Author(s):  
Xialin Sun ◽  
Tingwen Zhang ◽  
Yan Zhao ◽  
Enbo Cai ◽  
Hongyan Zhu ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Inhibitory Effect ◽  
Significant Inhibitory Effect

Panaxynol has significant inhibitory effect on CUMS-induced depression in mice.

scholarly journals Chemical Composition and in Vitro Antibacterial Activity of the Essential Oil of Minthostachys Mollis (Kunth) Griseb Vaught from the Venezuelan Andes

2009 ◽  
Vol 4 (7) ◽  
pp. 1934578X0900400 ◽  
Author(s):  
Flor D. Mora ◽  
María Araque ◽  
Luis B. Rojas ◽  
Rosslyn Ramírez ◽  
Bladimiro Silva ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Essential Oil ◽  
Chemical Constituents ◽  
Salmonella Typhi ◽  
Inhibitory Effect ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Significant Inhibitory Effect ◽  
In Vitro Antibacterial Activity

Chemical constituents of the essential oil from the leaves of Minthostachys mollis (Kunth) Griseb Vaught var. mollis collected in January 2008 at Tuñame, Trujillo State, Venezuela, were separated and identified by GCMS analysis. The essential oil was obtained by hydrodistillation and thirteen components (98.5% of the sample) were identified by comparison with the Wiley GCMS library data base. The two major components were pulegone (55.2%) and trans-menthone (31.5%). The essential oil showed a significant inhibitory effect against Gram-positive and Gram-negative bacteria, especially Bacillus subtilis and Salmonella typhi (4 μg/mL).

scholarly journals Pubinernoid A and Apo-9′-fucoxanthinone, Secondary Metabolites from a Gorgonian Coral Pinnigorgia sp

2016 ◽  
Vol 11 (6) ◽  
pp. 1934578X1601100
Author(s):  
Hsin-Huan Chang ◽  
Yu-Chia Chang ◽  
Wu-Fu Chen ◽  
Tsong-Long Hwang ◽  
Lee-Shing Fang ◽  
...  
Keyword(s):  
Secondary Metabolites ◽  
Spectroscopic Data ◽  
Spectroscopic Analysis ◽  
Inhibitory Effect ◽  
Human Neutrophils ◽  
Gorgonian Coral ◽  
First Report ◽  
Significant Inhibitory Effect ◽  
Animal Source

The structures of pubinernoid A (1) and apo-9′-fucoxanthinone (2), isolated from a gorgonian coral Pinnigorgia sp., were elucidated on the basis of spectroscopic analysis and by comparison of their spectroscopic data with those of known compounds. This is the first report of 1 and 2 from an animal source. Apo-9′-fucoxanthinone (2) displayed a significant inhibitory effect on the release of elastase by human neutrophils, with an IC50 value of 5.75 μM.

Roles of calcium and kinases in regulation of thrombin-stimulated preproendothelin-1 transcription

1996 ◽  
Vol 271 (5) ◽  
pp. H1918-H1925 ◽  
Author(s):  
T. A. Marsen ◽  
M. S. Simonson ◽  
M. J. Dunn
Keyword(s):  
Endothelial Cells ◽  
Inhibitory Effect ◽  
Ionophore A23187 ◽  
Tetraacetic Acid ◽  
Human Endothelial Cells ◽  
Mrna Induction ◽  
Significant Inhibitory Effect ◽  
Calmodulin Kinase ◽  
Dependent Signal ◽  
Dependent Pathway

The release of the vasoactive peptide endothelin-1 (ET-1) is Ca2+ dependent after thrombin stimulation; however, little is known about the pathways involved. We studied the importance of Ca(2+)-dependent signal transduction pathways on preproET-1 mRNA induction in human endothelial cells. Thrombin-mediated preproET-1 mRNA induction was inhibited after clamping of cytosolic free CA2+ concentration ([Ca2+]i) with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Chelation of extracellular Ca2+ with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid also had a significant inhibitory effect on the induction of preproET-1 mRNA. The Ca2+ ionophore A23187 induced constitutive as well as thrombin-stimulated preproET-1 mRNA expression. Mobilization of Ca2+ stores into the cytosol by inhibition of endoplasmic reticulum Ca(2+)-adenosinetriphosphatase with thapsigargin was effective also in inducing preproET-1 mRNA. Calmodulin antagonists W-7 and calmidazolium, as well as Ca2+/calmodulin-dependent kinase II inhibitor KN-62, significantly reduced thrombin-induced preproET-1 mRNA. Inhibition by cyclosporin A of the Ca(2+)-calmodulin-dependent phosphatase calcineurin potentiated constitutive preproET-1 mRNA. These data suggest that, in human endothelial cells, thrombin-mediated preproET-1 gene induction is regulated by a stimulatory Ca2+/calmodulin kinase II-dependent pathway.

scholarly journals Flavanol monomer-induced changes to the human faecal microflora

2007 ◽  
Vol 99 (4) ◽  
pp. 782-792 ◽  
Author(s):  
Xenofon Tzounis ◽  
Jelena Vulevic ◽  
Gunter G. C. Kuhnle ◽  
Trevor George ◽  
Jadwiga Leonczak ◽  
...  
Keyword(s):  
Carbon Sources ◽  
Inhibitory Effect ◽  
Distal Region ◽  
Gut Health ◽  
Significant Inhibitory Effect ◽  
Human Large Intestine ◽  
Faecal Bacteria ◽  
Induced Changes ◽  
Initial Conversion ◽  
Faecal Microflora

We have investigated the bacterial-dependent metabolism of ( − )-epicatechin and (+)-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the human large intestine. Incubation of ( − )-epicatechin or (+)-catechin (150 mg/l or 1000 mg/l) with faecal bacteria, led to the generation of 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone, 5-phenyl-γ-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (+)-catechin required its initial conversion to (+)-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (+)-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of theClostridium coccoides–Eubacterium rectalegroup,Bifidobacteriumspp. andEscherichia coli, as well as a significant inhibitory effect on the growth of theC. histolyticumgroup. In contrast, the effect of ( − )-epicatechin was less profound, only significantly increasing the growth of theC. coccoides–Eubacterium rectalegroup. These potential prebiotic effects for both (+)-catechin and ( − )-epicatechin were most notable at the lower concentration of 150 mg/l. As both ( − )-epicatechin and (+)-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (+)-catechin incubation may be linked to the bacterial conversion of (+)-catechin to (+)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions.

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