Search results for " Drug"
showing 10 items of 3138 documents
Mechanochemical synthesis of antifungal bis(benzoxaboroles)
2020
Several piperazine bis(benzoxaboroles) have been obtained both in solution as well as in the solid state. The environmentally friendly mechanochemical approach – hitherto not applied for the preparation of benzoxaboroles – was particularly beneficial in the case of two products afforded in low yields in solution. The in vitro studies showed high potential of the studied bis(fluorobenzoxaboroles) as antifungal agents, highlighting also the influence of the fluorine substituent position on their microbiological activity. The highest activity against A. niger, A. terreus, P. ochrochloron, C. tenuis and C. albicans was displayed by the analogue of the known benzoxaborole antifungal drug Kerydin…
Role of the Non-Canonical RNAi Pathway in the Antifungal Resistance and Virulence of Mucorales
2021
Mucorales are the causal agents for the lethal disease known as mucormycosis. Mortality rates of mucormycosis can reach up to 90%, due to the mucoralean antifungal drug resistance and the lack of effective therapies. A concerning urgency among the medical and scientific community claims to find targets for the development of new treatments. Here, we reviewed different studies describing the role and machinery of a novel non-canonical RNAi pathway (NCRIP) only conserved in Mucorales. Its non-canonical features are the independence of Dicer and Argonaute proteins. Conversely, NCRIP relies on RNA-dependent RNA Polymerases (RdRP) and an atypical ribonuclease III (RNase III). NCRIP regulates the…
Folate-mediated targeting of polymeric conjugates of gemcitabine.
2005
The synthesis of two new macromolecular prodrugs for active tumor targeting was set up. Gemcitabine (2'-deoxy-2',2'-difluorocytidine) was conjugated to alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) through succinyl or diglycolyl hydrolysable spacers. The targeting agent folic acid was attached to the macromolecular backbone through the aminocaproic spacer. The two conjugates [PHEA-(5'-succinylgemcitabine)-1'-carboxypentyl-folamide and PHEA-(5'-diglycolyl-gemcitabine)-1'-carboxypentyl-folamide], were purified and extensively characterised by spectroscopic (UV, IR and NMR) and chromatographic analyses to determine the correct chemical structure, the purity degree and the reaction yi…
Recent advances in computational design of potent aromatase inhibitors: open-eye on endocrine-resistant breast cancers.
2019
Introduction: The vast majority of breast cancers (BC) are estrogen receptor positive (ER+). The most effective treatments to fight this BC type rely on estrogen deprivation therapy, by inhibiting the aromatase enzyme, which performs estrogen biosynthesis, or on blocking the estrogens signaling path via modulating/degrading the estrogen's specific nuclear receptor (estrogen receptor-?, ER?). While being effective at early disease stage, patients treated with aromatase inhibitors (AIs) may acquire resistance and often relapse after prolonged therapies. Areas covered: In this compendium, after an overview of the historical development of the AIs currently in clinical use, and of the computati…
Oxidative stress of alternariol in Caco-2 cells
2014
Alternariol (AOH) is a mycotoxin produced by fungus Alternaria. It is found in a wide variety of fruits and cereals products. AOH is able to damage human health. The aim of this study was to evaluate the cytotoxicity of AOH in human colon adenocarcinoma (Caco-2) cells. Moreover, some events related to oxidative stress were evaluated: reactive oxygen species (ROS) generated by oxidation of 2',7'-dichlorodihydrofluorescein diacetate; peroxidation of lipid (LPO) by malondialdehyde (MDA) production; and antioxidant enzymatic capability of catalase (CAT) and superoxide dismutase (SOD). Cytotoxicity of AOH (from 3.125 to 100 μM) was determined during 24, 48 and 72 h of exposure by different endpo…
A new dual inhibitor of arachidonate metabolism isolated from Helichrysum italicum.
2003
Six acetophenones (1-6) and one gamma-pyrone (7), previously isolated from Helichrysum italicum, were tested for their ability to inhibit enzymatic and non-enzymatic lipid peroxidation, the stable 1,1-diphenyl-2-pycryl-hydrazyl free radical, superoxide scavenging and arachidonic acid metabolism. In addition, they were studied in different experimental models such as the chronic inflammation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA), the phospholipase A(2)-induced mouse paw oedema test, the carrageenan-induced mouse paw oedema test, and the writhing induced by acetic acid in the mouse. Of the assayed compounds, only 1 inhibited enzymatic lipid peroxidation but had no effect on no…
Nitic oxide promotes strong cytotoxicity of phenolic compounds against escherichia coli. The influence of antioxidant defenses
2003
[EN] The induction of mutagenic and cytotoxic effects by simple phenolics, including catechol (CAT), 3,4dihydroxyphenylacetic acid (DOPAC), hydroquinone (HQ), and 2,5-dihydroxyphenylacetic (homogentisic) acid (HGA), appears to occur through an oxidative mechanism based on the ability of these compounds to undergo autoxidation, leading to quinone formation with the production of reactive oxygen species. This is supported by the detection of such adverse effects in plate assays using Escherichia coli tester strains deficient in the OxyR function, but not in OxyR(+) strains. The OxyR protein is a redox-sensitive regulator of genes encoding antioxidant enzymes including catalase and alkyl hydro…
Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity.
2009
Strong evidence indicates that oxidative stress may be causally involved in the pathogenesis of Parkinson's disease. We have employed human dopaminergic neuroblastoma cells and rat primary mesencephalic neurons to assess the protective potential of three novel bisarylimine antioxidants on dopaminergic cell death induced by complex I inhibition or glutathione depletion. We have found that exceptionally low concentrations (EC(50) values approximately 20 nM) of these compounds (iminostilbene, phenothiazine, and phenoxazine) exhibited strong protective effects against the toxicities of MPP(+), rotenone, and l-buthionine sulfoximine. Investigating intracellular glutathione levels, it was found t…
Tumor Blood Flow and O2 Availability during Hemodilution
1984
An insufficient and heterogeneously distributed nutritive blood flow leads to an inadequate and nonuniform supply of O2 and substrates in many solid tumors (Vaupel, 1977, 1979, 1982). This deterioration of the supply conditions, which already occurs in very early growth stages and which is superimposed by a deterioration of diffusive transport during advanced growth stages, is paralleled by a decrease in the therapeutic efficacy of various cancer treatment modalities such as irradiation and chemotherapy with antiproliferative drugs. In the case of anticancer drugs, the efficiency may be reduced by affecting both pharmacokinetics and pharmacodynamics. In the latter case this is due to the de…
MONITORING OF ATYPICAL ANTIPSYCHOTIC DRUGS SUPPLIED BY THE PHARMACY OF FRATELLI PARLAPIANO HOSPITAL, RIBERA (AG), ITALY
2014
Mental disorders are among the worst and widespread health problems, they are associated with important repercussions on the psychosocial sphere and to high economic costs. Antipsychotic drugs used in treatments of these pathologies belong to different chemical classes, but associated to biochemical effects, pharmacological, and in part super imposable. A retrospective survey has been led on external patients, they were under antipsychotic drug treatments already in the archive and arrived to the attention of the Pharmacy of the F.lli Parlapiano Hospital, Ribera (AG), Italy in 2013. For each patient have been extrapolated: gender, date of birth, place of residence, ICD-9CM, pharmacological …