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Marc Martin

Publications and source records attributed to Marc Martin.

8 recordsLinked to original sources
PubMed2007

Mechanistic insights into stereoselective catalysis-the effects of counterions in a CuII-bissulfoximine-catalyzed Diels-Alder reaction.

The initial steps of an enantioselective Diels-Alder reaction catalyzed by a CuII-bissulfoximine complex were followed by EXAFS (EXAFS=extended X-ray absorption fine structure), EPR (EPR=electron paramagnetic resonance) spectroscopy (CW-EPR, FID-detected EPR, pulse ENDOR, HYSCORE; CW=continuous wave; ENDOR=electron nuclear double resonance; HYSCORE=hyperfine sublevel correlation; FID=free induction decay), and UV-visible spectroscopy. The complexes formed between the parent CuX2 (X=Cl-, Br-, TfO-, SbF6-) salts, the chiral bissulfoximine ligand (S,S)-1, and N-(1-oxoprop-2-en-1-yl)oxazolidin-2-one (2) as the substrate in CH2Cl2 were investigated in frozen and fluid solution. In all cases, penta- or hexacoordinated CuII centers were established. The complexes with counterions indicating high stereoselectivity (TfO- and SbF6-) reveal one unique species in which substrate 2 binds to pseudoequatorial positions (via O atoms), shifting the counterions to axial locations. On the other hand, those lacking stereoselectivity (X=Cl- and Br-) form two species in which the parent halogen anions remain at equatorial positions preventing the formation of geometries compatible with those found for X=TfO- and SbF6-.

Journal Article↗
PubMed2006

Structure-activity relationships in platelet-activating factor. Part 13: synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity.

HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained by modifying its piperazine substituents. The structure-activity relationship study shows that a better dual activity or even pure antiretroviral compounds can be obtained in this series.

Acquired Immunodeficiency Syndrome↗
PubMed2005

"Hook effect" in calcitonin immunoradiometric assay in patients with metastatic medullary thyroid carcinoma: case report and review of the literature.

CONTEXT: Calcitonin is a well-established tumor marker for medullary thyroid carcinoma (MTC). Because surgery is the only effective treatment for patients with MTC, the postoperative level of serum calcitonin will dictate whether residual disease was left behind and whether reintervention is necessary. RESULTS: We describe here the case of a 41-yr-old man with metastatic MTC. Despite extensive disease in the neck as well as metastatic lesions in the liver, his serum calcitonin, measured with a commercial one-step immunoradiometric assay, was only minimally elevated (244 ng/liter). After serial dilutions, a nonlinear relationship became evident, suggesting the presence of a "hook effect." Treatment of the serum with heterophilic blocking reagent revealed no change. Calcitonin was then measured with a different immunoradiometric assay and revealed a much higher level. Similar discrepancies were found in different samples from various patients when analyzed with different calcitonin immunoassays. CONCLUSION: To our knowledge, this is the first reported case of a phenomenon such as the hook effect in a calcitonin immunoradiometric assay in patients with MTC. Being aware of this phenomenon is important, because a low calcitonin result could give false reassurance to both the patient and the clinician and could dramatically change the prognosis of the patient.

Adult↗
PubMed2005

Involvement of IL-6 in the anti-human immunodeficiency virus activity of IFN-tau in human macrophages.

IFN-tau is a non-cytotoxic type I IFN responsible for maternal recognition of the foetus in ruminants. IFN-tau has been found to inhibit HIV replication more strongly than human IFN-alpha, particularly in human monocyte-derived macrophages, without associated toxicity. Ovine IFN-tau uses the same anti-viral cellular pathways as human IFN-alpha in human macrophages, principally inhibiting the early steps of the biological cycle of HIV, preventing the integration of HIV DNA into the host-cell genome. In this study, we investigated the immunomodulatory properties of IFN-tau in human macrophages. We found that IFN-tau increased the production of IL-10 and IL-6, but not of IL-1beta or tumour necrosis factor alpha, in unstimulated, LPS-stimulated and HIV-1/Ba-L-infected macrophages. We also found that treatment with IL-6 inhibited HIV replication. Moreover, the neutralization of IL-6 activity in the cell culture supernatants of IFN-tau-treated macrophages led to a decrease in the anti-retroviral effects of IFN-tau, suggesting that IL-6 was involved in the anti-viral activity induced by IFN-tau. By focusing on the very early steps of the biological cycle of HIV, we showed that IL-6 co-operated with IFN-tau to decrease intracellular HIV RNA levels 2 h after infection.

Animals↗
PubMed2004

Structure-activity relationships in platelet-activating factor. 12. Synthesis and biological evaluation of platelet-activating factor antagonists with anti-HIV-1 activity.

The HIV-1 central nervous system infection leads to the onset of neurological impairments called AIDS dementia complex (ADC). PAF plays an important role in this pathology, as it is an HIV-1-induced neurotoxin produced by infected or activated macrophages and microglia, in the brain. We previously reported that PAF-antagonists bearing a trisubstituted piperazine presented in vitro anti-HIV-1 activity in human macrophages. To improve the pharmacological activities of our lead compound, 1a, we modified its carbamate function and evaluated both its antiretroviral and anti-PAF activities. One carbamate derivative (10c) demonstrated a similar antiviral activity but a higher anti-PAF potency, whereas 4a, with an ureide function, presents an increased antiviral activity and can be considered as a pure antiretroviral drug, as it does not present PAF-antagonism. Moreover, we measured the ability of 1a to cross the blood-brain barrier, using the in situ mouse brain perfusion method and its plasmatic concentrations after iv and po administration. The transport parameter measured (K(in)) proves that 1a is able to cross this biological barrier, but a pharmacokinetic study reveals its weak bioavailability in rats.

Animals↗
PubMed2003

Spectroscopic investigations of bis(sulfoximine) copper(II) complexes and their relevance in asymmetric catalysis.

The structure of Cu(II) complex 3 formed within the course of a stereoselective Diels-Alder reaction was investigated by EXAFS, CW-EPR at X- and W-band, HYSCORE, pulsed ENDOR, and UV-vis spectroscopy. The experimental techniques indicate that the chiral bis(sulfoximine) ligand (S,S)-1 and the dienophile form a tetragonally distorted complex in CH(2)Cl(2). The ligand binds to the Cu(II) center via the imine nitrogens, whereas the dienophile interacts via the carbonyl oxygen atoms. The additional sites of the first coordination sphere are occupied by counterions and, presumably, solvent molecules. At the axial position, a triflate anion binds via an oxygen atom.

Journal Article↗
PubMed2003

Anti-human immunodeficiency virus activity of tau interferon in human macrophages: involvement of cellular factors and beta-chemokines.

Tau interferon (IFN-tau) is a noncytotoxic type I IFN responsible for maternal recognition of the fetus in ruminants. IFN-tau inhibits human immunodeficiency virus (HIV) replication more strongly than human IFN-alpha, particularly in human monocyte-derived macrophages. In this study performed in human macrophages, IFN-tau efficiently inhibited the early steps of the biological cycle of HIV, decreasing intracellular HIV RNA and inhibiting the initiation of the reverse transcription of viral RNA into proviral DNA. Two mechanisms induced by IFN-tau treatment in macrophages may account for this inhibition: (i) the synthesis of the cellular antiviral factors such as 2',5'-oligoadenylate synthetase/RNase L and MxA protein and (ii) an increased production of MIP-1alpha, MIP-1beta, and RANTES, which are natural ligands of CCR5, the principal coreceptor of HIV on macrophages. Our results suggest that IFN-tau induces the same antiviral pathways in macrophages as other type I IFNs but without associated toxicity.

Chemokines, CC↗