Spirooxindoles as Potential Pharmacophores Panda, Siva S; Jones, Rachel A; Bachawala, Praveen ...
Mini reviews in medicinal chemistry,
01/2017, Letnik:
17, Številka:
16
Journal Article
Recenzirano
The spirooxindole heterocyclic scaffold is found in many natural products and has been identified as an important bioactive agent.
Over the past few decades, various spirooxindole-containing ...compounds have been reported to possess biological properties and hence found in the structure of many synthetic pharmaceuticals. This mini-review describes the most promising examples of this class of compounds possessing biological activity including anticancer, anti-inflammatory, and antimicrobial activities.
The current review focuses on the biological activity of compounds containing the spirooxindole scaffold.
Most compact binary systems are expected to circularize before the frequency of emitted gravitational waves (GWs) enters the sensitivity band of the ground based interferometric detectors. However, ...several mechanisms have been proposed for the formation of binary systems, which retain eccentricity throughout their lifetimes. Since no matched-filtering algorithm has been developed to extract continuous GW signals from compact binaries on orbits with low to moderate values of eccentricity, and available algorithms to detect binaries on quasicircular orbits are suboptimal to recover these events, in this paper we propose a search method for detection of gravitational waves produced from the coalescences of eccentric binary black holes (eBBH). We study the search sensitivity and the false alarm rates on a segment of data from the second joint science run of LIGO and Virgo detectors, and discuss the implications of the eccentric binary search for the advanced GW detectors.
Injury, inflammation, and nerve damage initiate a wide variety of cellular and molecular processes that culminate in hyperexcitation of sensory nerves, which underlies chronic inflammatory and ...neuropathic pain. Using behavioral readouts of pain hypersensitivity induced by angiotensin II (Ang II) injection into mouse hindpaws, our study shows that activation of the type 2 Ang II receptor (AT2R) and the cell-damage-sensing ion channel TRPA1 are required for peripheral mechanical pain sensitization induced by Ang II in male and female mice. However, we show that AT2R is not expressed in mouse and human dorsal root ganglia (DRG) sensory neurons. Instead, expression/activation of AT2R on peripheral/skin macrophages (MΦs) constitutes a critical trigger of mouse and human DRG sensory neuron excitation. Ang II-induced peripheral mechanical pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral MΦs. Furthermore, AT2R activation in MΦs triggers production of reactive oxygen/nitrogen species, which
-activate TRPA1 on mouse and human DRG sensory neurons via cysteine modification of the channel. Our study thus identifies a translatable immune cell-to-sensory neuron signaling crosstalk underlying peripheral nociceptor sensitization. This form of cell-to-cell signaling represents a critical peripheral mechanism for chronic pain and thus identifies multiple druggable analgesic targets.
Pain is a widespread health problem that is undermanaged by currently available analgesics. Findings from a recent clinical trial on a type II angiotensin II receptor (AT2R) antagonist showed effective analgesia for neuropathic pain. AT2R antagonists have been shown to reduce neuropathy-, inflammation- and bone cancer-associated pain in rodents. We report that activation of AT2R in macrophages (MΦs) that infiltrate the site of injury, but not in sensory neurons, triggers an intercellular redox communication with sensory neurons via activation of the cell damage/pain-sensing ion channel TRPA1. This MΦ-to-sensory neuron crosstalk results in peripheral pain sensitization. Our findings provide an evidence-based mechanism underlying the analgesic action of AT2R antagonists, which could accelerate the development of efficacious non-opioid analgesic drugs for multiple pain conditions.
► Extraction of actinide ions viz. Am3+, Pu4+ and UO22+. ► TODGA in room temperature ionic liquids. ► Ion-exchange mechanism of extraction. ► Significantly enhanced separation factors.
Extraction ...behavior of several actinide ions viz. Am3+, Pu4+ and UO22+ was investigated using N,N,N′,N′-tetra-n-octyl diglycolamide (TODGA) as extractant in three different room temperature ionic liquids (RTIL), viz. C4mim+·NTf2- , C6mim+·NTf2- , and C8mim+·NTf2- as the diluents. The solvent systems containing TODGA in the RTILs were found to result in higher distribution ratios for all the actinides (trivalent, hexavalent, tetravalent) as compared to that containing n-dodecane as the diluent. Moreover, the distribution ratio values of the metal ions at lower acidities were found to decrease with increasing feed nitric acid concentration. Extraction was found to be independent of the anion of the aqueous phase. Mechanism of extraction of the actinides was found to be different compared to n-dodecane, molecular diluent. Cation-exchange was found to be the mechanism of extraction followed in RTILs. Effect of carbon chain length of alkyl groups of the RTILs conclusively proved the mechanism of extraction of the actinides by TODGA. Nature of extracted species was also found to differ from n-dodecane. Stripping studies were carried out using complexing agents such as EDTA, DTPA in guanidine carbonate or a buffer mixture.
Cirrhinus reba
(Hamilton, 1822) has gained high recognition in southern Asia for its nutritional and commercial benefits, although the carp is now facing productivity constraints. Probiotic-based ...captive breeding of the carp can be a promising technique to enhance the productivity and health status of the carp. The comprehensive study was performed on bacteria in the intestinal tract of
C. reba
. The total load of culturable bacteria in the gut of the carp was (8.34 ± 1.64) × 10
7
CFU/g comprising 19 different types of colonies. Most (73.7%) of the isolates were Gram-positive and rod-shaped bacteria. Among them, two intestinal isolates (PKS9 and PKS10) had shown significant antagonism against common fish pathogens namely,
Staphylococcus aureus
,
Vibrio harveyi
, and
Vibrio parahaemolyticus
. 16S rDNA sequencing identified the isolates PKS9 and PKS10 as
Bacillus paramycoides
(OM038513) and
Bacillus cereus
(OM033468), respectively. The isolates were determined to be biofilm formers, could persist in both acidic and alkaline environments, had high resistance to bile salts, possess surface hydrophobicity and auto-aggregation efficacy. The tests on pathogenicity and bio-safety confirmed the non-pathogenic nature of the isolates. Moreover, the strains had liberated extracellular enzymes and exhibited antioxidative properties. Hence, the isolates might be used as potential candidate probiotics for the cultivation of
C. reba
to enhance the nutritional and health status of the species. To the best of our knowledge, this is the first report analyzing the gut microbiota of Reba carp and establishing
B. paramycoides
as aquaculture probiotics.
The complement system significantly contributes to the development of inflammatory and neuropathic pain, but the underlying mechanisms are poorly understood. Recently, we identified the signaling ...pathway responsible for thermal hypersensitivity induced by the complement system component C5a. Here, we examine the mechanisms of another important action of C5a, induction of mechanical hypersensitivity. We found that intraplantar injection of C5a produced a dose-dependent mechanical sensitization and that this effect was blocked by chemogenetic ablation of macrophages in both male and female mice. Knockout of TRPV1 or pretreatment with the TRPV1 antagonists, AMG9810 or 5'-iodoresiniferatoxin (5'-IRTX), significantly reduced C5a-induced mechanical sensitization. Notably, local administration of 5'-IRTX 90 minutes after C5a injection resulted in a slow, but complete, reversal of mechanical sensitization, indicating that TRPV1 activity was required for maintaining C5a-induced mechanical hypersensitivity. This slow reversal suggests that neurogenic inflammation and neuropeptide release may be involved. Indeed, pretreatment with a calcitonin gene-related peptide (CGRP) receptor antagonist (but not an antagonist of the neurokinin 1 receptor) prevented C5a-induced mechanical sensitization. Furthermore, intraplantar injection of CGRP produced significant mechanical sensitization in both wild-type and TRPV1 knockout mice. Taken together, these findings suggest that C5a produces mechanical sensitization by initiating macrophage-to-sensory-neuron signaling cascade that involves activation of TRPV1 and CGRP receptor as critical steps in this process.
Transport behaviour of
137Cs from nitric acid feed was investigated using cellulose triacetate plasticized polymer inclusion membrane (PIM) containing several crown ether carriers viz. ...di-benzo-18-crown-6 (DB18C6), di-benzo-21-crown-7 (DB21C7) and di-
tert-butylbenzo-18-crown-6 (DTBB18C6). The PIM was prepared from cellulose triacetate (CTA) with various crown ethers and plasticizers. DTBB18C6 and tri-
n-butyl phosphate (TBP) were found to give higher transport rate for
137Cs as compared to other carriers and plasticizers. Effect of crown ether concentration, nitric acid concentration, plasticizer and CTA concentration on the transport rate of Cs was also studied. The Cs selectivity with respect to various fission products obtained from an irradiated natural uranium target was found to be heavily dependent on the nature of the plasticizer. The present work shows that by choosing a proper plasticizer, one can get either good transport efficiency or selectivity. Though TBP plasticized membranes showed good transport efficiency, it displayed poor selectivities. On the other hand, an entirely opposite separation behaviour was observed with 2-nitrophenyloctylether (NPOE) plasticized membranes suggesting the possible application of the later membranes for the removal of bulk
137Cs from the nuclear waste. The stability of the membrane was tested by carrying out transport runs for nearly 25 days.
Cirrhinus reba
(Hamilton, 1822) has gained high recognition in southern Asia for its nutritional and commercial benefits, although the carp is now facing productivity constraints. Probiotic-based ...captive breeding of the carp can be a promising technique to enhance the productivity and health status of the carp. The comprehensive study was performed on bacteria in the intestinal tract of
C. reba
. The total load of culturable bacteria in the gut of the carp was 8.34 ± 1.64 × 10
7
CFU/g comprising 19 different types of colonies. Most (73.7%) of the isolates were Gram-positive and rod-shaped bacteria. Among them, two intestinal isolates (PKS9 and PKS10) had shown significant antagonism against common fish pathogens namely,
Staphylococcus aureus
,
Vibrio harveyi
, and
Vibrio parahaemolyticus
. 16S rDNA sequencing identified the isolates PKS9 and PKS10 as
Bacillus paramycoides
(OM038513) and
Bacillus cereus
(OM033468), respectively. The isolates were determined to be biofilm formers, could persist in both acidic and alkaline environments, had high resistance to bile salts, possess surface hydrophobicity and auto-aggregation efficacy. The tests on pathogenicity and bio-safety confirmed the non-pathogenic nature of the isolates. Moreover, the strains had liberated extracellular enzymes and exhibited antioxidative properties. Hence, the isolates might be used as potential candidate probiotics for the cultivation of
C. reba
to enhance the nutritional and health status of the species. To the best of our knowledge, this is the first report analyzing the gut microbiota of Reba carp and establishing
B. paramycoides
as aquaculture probiotics.
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