Search results for "Potency"
showing 10 items of 122 documents
Modeling caspase-1 inhibition: Implications for catalytic mechanism and drug design.
2019
Abstract The metabolic product of caspase-1, IL-1β, is an important mediator in inflammation and pyroptosis cell death process. Alzheimer's disease, septic shock and rheumatoid arthritis are IL-1β mediated diseases, making the caspase-1 an interesting target of pharmacological value. Many inhibitors have been developed until now, most of them are peptidomimetic with improved potency. In the present study, all-atom molecular dynamics simulations and the MM/GBSA method were employed to reproduce and interpret the results obtained by in vitro experiments for a series of inhibitors. The analysis shows that the tautomeric state of the catalytic His237 impact significantly the performance of the …
A Hyaluronic acid-pentamidine bioconjugate as macrophage mediated drug targeting delivery system for the treatment of Leishmaniasis
2015
Leishmaniasis is still a serious public health problem worldwide, especially in tropical areas where this infectious disease is endemic. The most severe form of the disease (i.e. visceral) can claim victims if left untreated and the few accessible drugs have several drawbacks including major side effects and parenteral administration. In this context, the investigation of new delivery modalities which might reduce the toxicity and increase the bioavailability of the drugs currently on the market represents a valid strategy to counter these problems. Herein we present the development of a macrophage mediated drug targeting delivery system by conjugating the anti-leishmanial drug pentamidine …
Prediction of sweetness potency from sweet taste receptor dose-response curves
2021
International audience
Defining the genomic signature of totipotency and pluripotency during early human development.
2013
The genetic mechanisms governing human pre-implantation embryo development and the in vitro counterparts, human embryonic stem cells (hESCs), still remain incomplete. Previous global genome studies demonstrated that totipotent blastomeres from day-3 human embryos and pluripotent inner cell masses (ICMs) from blastocysts, display unique and differing transcriptomes. Nevertheless, comparative gene expression analysis has revealed that no significant differences exist between hESCs derived from blastomeres versus those obtained from ICMs, suggesting that pluripotent hESCs involve a new developmental progression. To understand early human stages evolution, we developed an undifferentiation netw…
Synthesis and biological activity of novel sialyl-lewisX conjugates
1996
Abstract Novel sialyl Lewis X conjugates have been synthesized and evaluated as inhibitors of E- and P-selectin mediated cell adhesion in cell culture assays. The most potent conjugate in the static inhibition assays exhibited a significant and dose-dependent pharmacological potency as inhibitor of the edotoxin-induced leukocyte adhesion to the endothelium of postcapillary venules in rats.
Naturally occurring hemolysins in the coelomic fluid of Holothuria polii delle chiaie (Echinodermata).
1979
Abstract The coelomic fluid of Holothuria polii D.Ch contains hemolytic activity against erythrocytes of several vertebrate species. The hemolytic potency depends upon calcium ion concentration and varies according to erythrocyte source and cell number in the reaction mixture. Absorption experiments with formalinized rabbit erythrocytes suggest that hemolytic activity is not specific. Its heat lability, water insolubility at low pH values, and sensitivity to proteolytic enzymes suggest that hemolytic activity resides in protein molecules. The activity, maximal in alkaline media, appears to depend up time and temperature.
On sigma-subnormal subgroups of factorised finite groups
2020
Abstract Let σ = { σ i : i ∈ I } be a partition of the set P of all prime numbers. A subgroup X of a finite group G is called σ-subnormal in G if there is chain of subgroups X = X 0 ⊆ X 1 ⊆ ⋯ ⊆ X n = G with X i − 1 normal in X i or X i / C o r e X i ( X i − 1 ) is a σ i -group for some i ∈ I , 1 ≤ i ≤ n . In the special case that σ is the partition of P into sets containing exactly one prime each, the σ-subnormality reduces to the familiar case of subnormality. If a finite soluble group G = A B is factorised as the product of the subgroups A and B, and X is a subgroup of G such that X is σ-subnormal in 〈 X , X g 〉 for all g ∈ A ∪ B , we prove that X is σ-subnormal in G. This is an extension…
Cytotoxic effects of mycotoxin combinations in mammalian kidney cells
2011
The cytotoxicity of three Fusarium mycotoxins (beauvericin, deoxynivalenol and T-2 toxin) has been investigated using the NR assay, after 24, 48 and 72h of incubation. The IC(50) values ranged from 6.77 to 11.08, 3.30 to 10.00 and 0.004 to 0.005 for beauvericin, deoxynivalenol and T-2 toxin, respectively. Once the potential interaction has been detected, a quantitative assessment is necessary to ensure and characterize these interactions, that is, each mycotoxin contributes to the toxic effect in accord with its own potency. Combination of mycotoxins was determined in Vero cells after 24, 48 and 72h of exposure. Isobolograms and median effect method of Chou and Talalay were used to assess t…
Highly potent artemisinin-derived dimers and trimers: Synthesis and evaluation of their antimalarial, antileukemia and antiviral activities
2015
New pharmaceutically active compounds can be obtained by modification of existing drugs to access more effective agents in the wake of drug resistance amongst others. To achieve this goal the concept of hybridization was established during the last decade. We employed this concept by coupling two artemisinin-derived precursors to obtain dimers or trimers with increased in vitro activity against Plasmodiumfalciparum 3D7 strain, leukemia cells (CCRF-CEM and multidrug-resistant subline CEM/ADR5000) and human cytomegalovirus (HCMV). Dimer 4 (IC50 of 2.6 nM) possess superior antimalarial activity compared with its parent compound artesunic acid(3) (IC50 of 9.0 nM). Dimer5 and trimers6 and 7 disp…
Selective MicroRNA-Offset RNA Expression in Human Embryonic Stem Cells
2015
Small RNA molecules, including microRNAs (miRNAs), play critical roles in regulating pluri-potency, proliferation and differentiation of embryonic stem cells. miRNA-offset RNAs (moRNAs) are similar in length to miRNAs, align to miRNA precursor (pre-miRNA) loci and are therefore believed to derive from processing of the pre-miRNA hairpin sequence. Recent next generation sequencing (NGS) studies have reported the presence of moRNAs in human neurons and cancer cells and in several tissues in mouse, including pluripotent stem cells. In order to gain additional knowledge about human moRNAs and their putative development-related expression, we applied NGS of small RNAs in human embryonic stem cel…