Search results for "mimetics"

Adrenergic Stimulation of Cyclic GMP Formation Requires NO-Dependent Activation of Cytosolic Guanylate Cyclase in Rat Pinealocytes

1993

Cyclic GMP (cGMP) formation in rat pinealocytes is regulated through a synergistic dual receptor mechanism involving beta- and alpha 1-adrenergic receptors. The effects of NG-monomethyl-L-arginine (NMMA), which inhibits nitric oxide (NO) synthase and NO-mediated activation of cytosolic guanylate cyclase, and methylene blue (MB), which inhibits cytosolic guanylate cyclase, were investigated in an attempt to understand the role of NO in adrenergic cGMP formation. Both NMMA and MB inhibited beta-adrenergic stimulation of cGMP formation as well as alpha 1-adrenergic potentiation of beta-adrenergic stimulation of cGMP formation, whereas they had no effect in unstimulated pinealocytes. The inhibi…

The interferance of muscarinic receptors with the noradrenaline release from sympathetic nerve endings caused by nicotinic agents.

1968

Characterization of choline efflux from the perfused heart at rest and after muscarine receptor activation.

1986

The resting efflux of choline from perfused chicken hearts varied from 0.4 to 2.6 nmol/g min, but was constant for at least 80 min in the individual experiments. The rate of choline efflux was found to be equal to the rate of choline formation in the heart, which, from the following reasons, was essentially due to hydrolysis of choline phospholipids. Cardiac content of choline phospholipids (7,200 nmol/g) was much higher than that of acetylcholine (5.5 nmol/g). Resting release of acetylcholine was 0.016 nmol/g min and, after inhibition of cholinesterase, only about 0.1 nmol/g min. Resting efflux of choline was reduced by mepacrine, a phospholipase A2 inhibitor, by perfusion with a Ca2+-free…

Advances in surfaces and osseointegration in implantology. Biomimetic surfaces

2015

The present work is a revision of the processes occurring in osseointegration of titanium dental implants according to different types of surfaces -namely, polished surfaces, rough surfaces obtained from subtraction methods, as well as the new hydroxyapatite biomimetic surfaces obtained from thermochemical processes. Hydroxyapatite’s high plasma-projection temperatures have proven to prevent the formation of crystalline apatite on the titanium dental implant, but lead to the formation of amorphous calcium phosphate (i.e., with no crystal structure) instead. This layer produce some osseointegration yet the calcium phosphate layer will eventually dissolve and leave a gap between the bone and …

IAP proteins as targets for drug development in oncology.

2013

The inhibitors of apoptosis (IAPs) constitute a family of proteins involved in the regulation of various cellular processes, including cell death, immune and inflammatory responses, cell proliferation, cell differentiation, and cell motility. There is accumulating evidence supporting IAP-targeting in tumors: IAPs regulate various cellular processes that contribute to tumor development, such as cell death, cell proliferation, and cell migration; their expression is increased in a number of human tumor samples, and IAP overexpression has been correlated with tumor growth, and poor prognosis or low response to treatment; and IAP expression can be rapidly induced in response to chemotherapy or …

Hormesis: Decoding Two Sides of the Same Coin

2015

In the paradigm of drug administration, determining the correct dosage of a therapeutic is often a challenge. Several drugs have been noted to demonstrate contradictory effects per se at high and low doses. This duality in function of a drug at different concentrations is known as hormesis. Therefore, it becomes necessary to study these biphasic functions in order to understand the mechanistic basis of their effects. In this article, we focus on different molecules and pathways associated with diseases that possess a duality in their function and thus prove to be the seat of hormesis. In particular, we have highlighted the pathways and factors involved in the progression of cancer and how t…

Synthesis and Molecular Modeling Studies of Derivatives of a Highly Potent Peptidomimetic Vinyl Ester as Falcipain-2 Inhibitors

2012

Herein we report the synthesis of a set of constrained peptidomimetics endowed with an electrophilic vinyl ester warhead and structurally related to a previously identified lead compound, a potent and irreversible inhibitor of falcipain-2 (FP-2). FP-2 is the main hemoglobinase of the malaria parasite P. falciparum. The new compounds were evaluated for their inhibition against FP-2, and the results were rationalized on the basis of docking experiments. These studies underscore the pivotal role of both the ester function at the P1' site and the trifluoromethyl group of the P3 side chain in determining the correct orientation of the Michael acceptor warhead in the catalytic site, and as a cons…

Synthesis of Hybrid Tripeptide Peptidomimetics Containing Dehydroamino Acid and Aminophosphonic Acid in the Chain and Evaluation of Their Activity to…

2021

Synthesis of a new group of hybrid phosphonodehydropeptides composed of glycyl-(Z)-dehydrophenylalanine and structurally variable aminophosphonates alongside with investigations of their activity towards cathepsin C are presented. Obtained results suggest that the introduction of (Z)- dehydrophenylalanine residue into the short phosphonopeptide chain does induce the ordered conformation. Investigated peptides appeared to act as weak or moderate inhibitors of cathepsin C.

Synthesis and biological evaluation of novel peptidomimetics as rhodesain inhibitors

2016

Novel rhodesain inhibitors were developed by combining an enantiomerically pure 3-bromoisoxazoline warhead with a 1,4-benzodiazepine scaffold as specific recognition moiety. All compounds were proven to inhibit rhodesain with Ki values in the low-micromolar range. Their activity towards rhodesain was found to be coupled to an in vitro antitrypanosomal activity, with IC50 values ranging from the mid-micromolar to a low-micromolar value for the most active rhodesain inhibitor (R,S,S)-3. All compounds showed a good selectivity against the target enzyme since all of them were proven to be poor inhibitors of human cathepsin L. Novel rhodesain inhibitors were developed by combining an enantiomeri…

Cognitive Mimetics and Human Digital Twins : Towards Holistic AI Design

2023

AI is replacing and supporting people in many intelligence-requiring tasks. Therefore, it is essential to consider the conceptual grounds of designing future technical artefacts and technologies for practical use. We are developing two new practical design tools: cognitive mimetics and human digital twins for AI designers. Cognitive mimetics analyses human information processing to be mimicked by intelligent technologies. Human digital twins provide a tool for modelling what people do based on the results of cognitive mimetics. Together they provide a new way of designing intelligent technology in individual tasks and industrial contexts. nonPeerReviewed