Publications

ChemInform Abstract: Discovery of Small Molecular Inhibitors Targeting HIV‐1 gp120—CD4 Interaction Drived from BMS‐378806

Abstract Review: 51 refs.

Piégeage cohérent de population sur des atomes froids

National audience

Prevalence and origin of HIV-1 group M subtypes among patients attending a Belgian hospital in 1999

Development of fluorine-substituted NH2-biphenyl-diarylpyrimidines as highly potent non-nucleoside reverse transcriptase inhibitors: Boosting the safety and metabolic stability

Our recent studies for nonnucleoside reverse transcriptase inhibitors identified a highly potent compound JK-4b against WT HIV-1 (EC₅₀ = 1.0 nmol/L), but the poor metabolic stability in human liver microsomes (<i>t</i> _1/2 = 14.6 min) and insufficient selectivity (SI = 2059) with high cytotoxicity (CC₅₀ = 2.08 μmol/L) remained major issues associated with JK-4b. The present efforts were devoted to the introduction of fluorine into the biphenyl ring of JK-4b, leading to the discovery of a novel series of fluorine-substituted NH₂-biphenyl-diarylpyrimidines with noticeable inhibitory activity toward WT HIV-1 strain (EC₅₀ = 1.8-349 nmol/L). The best compound <b>5t</b> in this collection (EC₅₀ = 1.8 nmol/L, CC₅₀ = 117 μmol/L) was 32-fold in selectivity (SI = 66,443) compared to JK-4b and showed remarkable potency toward clinically multiple mutant strains, such as L100I, K103N, E138K, and Y181C. The metabolic stability of <b>5t</b> was also significantly improved (<i>t</i> _1/2 = 74.52 min), approximately 5-fold higher than JK-4b in human liver microsomes (<i>t</i> _1/2 = 14.6 min). Also, <b>5t</b> possessed good stability in both human and monkey plasma. No significant <i>in vitro</i> inhibition effect toward CYP enzyme and hERG was observed. The single-dose acute toxicity test did not induce mice death or obvious pathological damage. These findings pave the way for further development of <b>5t</b> as a drug candidate.

Palladium-catalyzed synthesis of [E]-6-(2-acylvinyl)uracils and [E]-6-(2-acylvinyl)-1-[(2-hydroxyethoxy)methyl]uracils—their antiviral and cytotoxic activities

Synthesis and Biological Evaluation of a Series of Substituted Pyridine-C-Nucleosides. Part V: 3-Chloro-4-(D-Ribofuranosyl)Pyridine and 3-(D-Ribofuranosyl)-2-Pyridone

Abstract The total synthesis of 3-chloro-4-(D-ribofuranosyl)-pyridine and 3-(D-ribo-furanosyl)-2-pyridone was elaborated using the appropriate lithiopyridines and 2,4:3,5-di-O-benzylidene-aldehydo-D-ribose. The conformation of these compounds was investigated by 360 MHz 1H-NMR. The compounds were evaluated as α,β-mixtures for their antiviral and cytostatic properties. However, no significant biological activity was found.

Evaluation of antiviral activity against human herpesvirus 8 (HHV-8) and Epstein–Barr virus (EBV) by a quantitative real-time PCR assay

Synthesis and biological activity of some 4-substituted 1-[1-(2,3-dihydroxy-1-propoxy)methyl-1,2,3-triazol-(4 &amp; 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines

The Acyclic Nucleoside Phosphonates (ANPs): Antonin Holy's Legacy (2012 - 2018)

The influence of changing inclination ngle and screw angle of the tool orientation on the surface quality in five-axis milling

No abstract is provided for this article.

Modes of action of interferon and analogues of 2-5A, a mediator of interferon action

In the last few years, several different interferons have been described, cloned, sequenced, expressed in heterologous systems and purified to homogeneity (Weissmann et al., 1982; Kingsman & Kingsman, 1983). In particular for human interferons there exists at least thirteen subtypes of IFN-α, one IFN-β and one IFN-γ. All these molecular species and some of their recombinant hybrids show a number of common biological properties but also distinctive antiviral (Weck et al., 1981; Kingsman & Kingsman, 1983) and other activities (Rehberg et al., 1982; Pestka et al., 1983b). Recombinant DNA technology has substantially contributed to the study of the mechanism of action of interferon and will probably continue to do so in the future by allowing a detailed analysis of the regulation and site-directed mutagenesis of IFN-induced proteins.

Synthesis, Anti-Tuberculosis and Antiviral Activity of Novel 2-isonicotinoylhydrazono-5-arylidene-4-thiazolidinones

This paper describes the synthesis and structural elucidation of some novel N'-[5-(substituted benzylidene)-3-alkyl-4-oxo-1,3-thiazolidin-2-ylidene]isonicotinohydrazides and evaluation of their chemotherapeutic potency. The most potent derivative demonstrated an IC90 value of 2.039 µg/ml and an IC50 value of 1.267 µg/ml against M. Tuberculosis H37Rv while one of our compounds inhibited cytopathicity of HIV-1 (IIIB) by 50% at 8.73 µg/ml and other two derivatives were found active against either thymidine kinase positive or deficient strains of varicella-zoster virus with IC50 values of 2.0 and 1.8 µg/ml.

Pyridazines 92. Synthesis of dialkyldipyridazinodiazepinones as potential HIV‐1 reverse transcriptase inhibitors

Abstract Two methods for the preparation of dialkylsubstituted dipyridazino[4,3‐ b :3′,4′‐ e ][1,4]diazepinones and dipyridazino[3,4‐ b :3′,4′‐ e ][1,4]diazepinones are reported. The new compounds were evaluated for their inhibitory effects against the replication of human immunodeficiency virus [HIV‐1(III B ) and HIV‐2(ROD)] in MT‐4 cells.

Different prevalences of resistance-related mutations in treatment-naïve patients carrying HIV-1 subtype B compared to other subtypes

Feedback control of Selective Laser Melting using optical sensors

Synthese und antivirale Aktivität von 2,3(1H, 4H)‐Chinoxalindion‐Derivaten

Abstract Bei unserer Suche nach neuen Virustatika haben wir 2.3(1H,4H)‐Chinoxalindion‐Derivate synthetisiert und auf ihre antivirale Aktivität gegen verschiedene Stämme des Virus Herpes Simplex Typ 1 und Typ 2, gegen Vaccinia Viren und gegen Vesicular Stomatitis Viren getestet. Keine der Verbindungen zeigte eine signifikante antivirale Aktivität im Vergleich mit 5‐Ethyl‐2′‐desoxyuridin (EtUdR).

Monitoring and adaptive control of CO2 laser flame cutting

In this paper a real-time control and optimization system for laser flame cutting of thick plates of mild steel is presented. The proposed system consists of two subsystems, namely a process monitoring and a control and optimization module. The process monitoring module evaluates the cut quality by measuring a set of sensing parameters, which are well-correlated with different quality characteristics of the cut surface. The applicability of different optical sensors (photodiodes and a NIRcamera) has been investigated. An overview of the most suitable set of sensing parameters is presented. The correlations between different quality deteriorations and the sensing parameters are mentioned as well as the reasons for these correlations. The real-time control and optimization module is implemented as an expert system with a dual functionality. On the one hand, it compares the sensing parameters with predefined thresholds and assigns one of the predefined quality classes to the instantaneous cut quality. On the other hand, it modifies the cutting parameters based on the predefined set of interpretable rules corresponding to the identified quality class. The obtained results prove the effectiveness of the chosen approach in terms of increased autonomy, productivity, and efficiency of the process, as well as elimination of the need for manual quality control and the possibility to automatically generate quality reports.

Understanding the Laser Sintering of Polymers at Microscale Level by Using X-Ray Computed Tomography

No abstract is provided for this article.