AMT hydrochloride

The nanocrystalline coordination polymer of AMT-Ag for an effective detection of ciprofloxacin hydrochloride in pharmaceutical formulation and biological fluid.[Pubmed:27236138]

Biosens Bioelectron. 2016 Nov 15;85:529-535.

The present report highlights a cost effective and portable AMT-Ag nanocrystalline coordination polymer (NCCP) based electrochemical sensor for an efficient sensing of biologically active drug molecule ciprofloxacin hydrochloride (CFX). The AMT-Ag NCCP, is synthesized using an easily accessible organic ligand 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) with silver nitrate. In the infinite polymer array of AMT-Ag, silver (I) centers are bridged by tecton AMT through the exocyclic thiol and amino linkage. A successful ultratrace detection of CFX has been achieved due to the prominent electron channeling through the pores of polymeric nano-crystallites. The efficient charge transfer arises at the interface of electrolyte and AMT-Ag nano-crystals anchored electrode through hydrophobic interaction and pi-pi electron coupling. The voltammogram reveals the critical redox features of CFX and provides a clear representation about the steps involved in the AMT-Ag assisted oxidation of CFX. This specific signature further applied in the voltammetric assay of CFX in pharmaceutical formulation (eye drops) and biological fluid (urine) by a significantly high sensitivity (0.002microA/microM and 0.007microA/microM) and detection limit (22nM and 60nM) respectively without any interference. Therefore, the developed AMT-Ag NCCP could serve as a highly valuable platform for the fabrication of high-performance electrochemical sensors for the detection of biologically important drug molecules.

Nitric oxide signaling in stretch-induced apoptosis of neonatal rat cardiomyocytes.[Pubmed:16877524]

FASEB J. 2006 Sep;20(11):1883-5.

Pressure overload associated with hypertension is an important pathological factor leading to heart remodeling and ultimately heart failure partially due to cardiomyocyte apoptosis. Here we show that endogenous NO signaling plays a critical role in mechanical stretch-induced cardiomyocyte apoptosis. Mechanical stretch induced elevated expression of both eNOS and inducible NO synthase (iNOS) and increased synthesis of NO. A sustained increase in iNOS expression was also found in hearts of hypertensive rats in vivo. Blockade of NO signaling by inhibitors of NOS (L-NAME and AMT) or downstream guanylyl cyclase (ODQ) strongly inhibited stretch-induced apoptosis, mitochondria depolarization, and cytochrome c release, suggesting that NO is required in stretch-induced cardiomyocyte apoptosis. The expression of iNOS, but not eNOS, was blocked by L-NAME and ODQ, indicating that the iNOS induction is NO dependent. The initial elevation of NO is likely due to Ca(2+)-dependent activation of eNOS because elimination of intracellular calcium by EGTA-AM inhibited both iNOS induction and NO elevation. Other calcium signaling inhibitors (nifedipine, ryanodine, thapsigargin, and ionic gadolinium) also attenuated the initial NO elevation. These data indicate that mechanical signals initiate Ca(2+)-dependent NO synthesis, which is further amplified by activation of NO-induced iNOS expression, to regulate cardiomyocyte apoptosis.

Inhibition of sarcoplasmic reticular function by chronic interleukin-6 exposure via iNOS in adult ventricular myocytes.[Pubmed:15845578]

J Physiol. 2005 Jul 15;566(Pt 2):327-40.

Interleukin (IL)-6 has been shown to decrease cardiac contractility via a nitric oxide synthase (NOS)-dependent pathway during acute exposure. We previously reported that IL-6 decreases contractility and increases inducible NOS (iNOS) in adult rat ventricular myocytes (ARVM) after 2 h exposure. The goal of this study was to investigate the cellular mechanism underlying this chronic IL-6-induced negative inotropy and the role of iNOS. Pretreatment for 2 h with 10 ng ml-1 IL-6 decreased the kinetics of cell shortening (CS) and contractile responsiveness to Ca2+o ([Ca2+]o from(0) to 2 mM) in ARVM. We first examined whether IL-6 reduced Ca2+ influx via L-type Ca2+ -channel current (ICa,L). Whole-cell ICa,L in ARVM was measured under conditions similar to those used for CS measurements, and it was found to be unaltered by IL-6. The sarcoplasmic reticular (SR) function was then assessed by examining postrest potentiation (PRP) and caffeine responsiveness of CS. Results showed that treatment with IL-6 for 2 h significantly decreased PRP, which was concomitant with a decrease in the phosphorylation of phospholamban. Following removal of IL-6, PRP and responsiveness to 10 mM caffeine were also reduced. Meanwhile, the IL-6-induced increase in nitric oxide (NO) production after 2 h (but not 1 h) was abolished by NG-monomethyl-l-arginine (l-NMMA) and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; a selective inhibitor of iNOS). Furthermore, IL-6-elicited suppressions of PRP and responsiveness to caffeine and Ca2+o were abolished by L-NMMA and AMT. Thus, these results suggest that activation of iNOS mediates IL-6-induced inhibition of SR function in ARVM during chronic exposure.

Novel potent and selective inhibitors of inducible nitric oxide synthase.[Pubmed:7536889]

Mol Pharmacol. 1995 Apr;47(4):831-4.

We have identified two novel potent and selective inhibitors of inducible nitric oxide synthase, S-ethylisothiourea and 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine. Ki values of 14.7 nM for S-ethylisothiourea and 4.2 nM for 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine were obtained with partially purified preparations of inducible nitric oxide synthase. These compounds demonstrate about 1000-fold greater potency than prototypical inhibitors, and the inhibitions are 10-40-fold more selective for murine inducible nitric oxide synthase, compared with the rat neuronal and bovine endothelial isoforms of nitric oxide synthase. These compounds also potently inhibit the nitric oxide synthase activity in intact J774 mouse macrophages. The inhibition is competitive with the substrate L-arginine and reversible in both enzymatic and intact cell assays. These potent and selective inhibitors of inducible nitric oxide synthase may have potential therapeutic applications in the treatment of inflammatory and autoimmune diseases.