Publications

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

Discovery of Dihydro‐Alkyloxy‐Benzyl‐Oxopyrimidines as Promising Anti‐Influenza Virus Agents

A series of novel dihydro-alkyloxy-benzyl-oxopyrimidine derivatives were synthesized and evaluated for their activity against influenza virus in Madin-Darby canine kidney cells. Four dihydro-alkyloxy-benzyl-oxopyrimidine derivatives (4a1, 4a2, 4a3, and 4d1) showed potent activity against influenza virus. Among them, compound 4a3 was the most promising lead with broad activity against influenza A (antiviral EC(50) values of 9 and 18 μm for the A/H1N1 and A/H3N2 subtype, respectively) and influenza B viruses (EC(50) : 33 μm). The antiviral mechanism of action of these dihydro-alkyloxy-benzyl-oxopyrimidine derivatives must be quite different from that of the currently approved anti-influenza virus drugs that target the viral M2 or neuraminidase proteins. The dihydro-alkyloxy-benzyl-oxopyrimidine derivatives represent a new avenue for further optimization and development of novel anti-influenza virus agents.

Novel ribofuranosylnucleoside lead compounds for potent and selective inhibitors of mitochondrial thymidine kinase-2

The ribonucleoside analogues (E)-5-(2-bromovinyl)uridine (5-BV-Urd) and 3´-spiro-(4´-amino-1´,2´-oxathiole-2´,2´-dioxide)-5-methyluridine (3´-AOD-5-MeUrd) emerged as potent and selective competitive inhibitors of mitochondrial thymidine kinase (TK)-2 with respect to thymidine (Ki/Km values of 9.0 and 1.2 respectively). Cytosolic TK-1 did not show measurable affinity for these compounds. [32P]Phosphate transfer studies from [γ-32P]ATP to 5-BV-Urd and 3´-AOD-5-MeUrd revealed extremely poor substrate activity but potent inhibitory potential of the compounds. It was concluded that the ribonucleosides 5-BV-Urd and 3´-AOD-5-MeUrd represent two new lead compounds for potent and selective inhibitors of mitochondrial TK-2.

Inhibitory effect of dextran sulfate and heparin on the replication of human immunodeficiency virus (HIV) in vitro

Synthesis, antimycobacterial, antiviral, antimicrobial activities, and QSAR studies of isonicotinic acid-1-(substituted phenyl)-ethylidene/cycloheptylidene hydrazides

Synthesis and biological evaluation of pyridazine derivatives as novel HIV-1 NNRTIs

A study of antitemplate inhibition of mammalian, bacterial and viral DNA polymerases by 2- and 2′-substituted derivatives of polyadenylic acid

Sydnone Sulfonamide Derivatives as Antibacterial, Antifungal, Antiproliferative and Anti-HIV Agents

Synthesis and evaluation of the biological activity of N′-[2-oxo-1,2 dihydro-3H-indol-3-ylidene] benzohydrazides as potential anticancer agents

New<italic>N</italic>′-[2-oxo-1,2-dihydro-3<italic>H</italic>-indol-3-ylidene]benzohydrazide derivatives were synthesized and evaluated for their cytotoxic properties against murine leukemia, L1210, human leukemia, REH, K562 and CEM and human cervix carcinoma, HeLa cells.

Synthesis and Antiviral and Antineoplastic Activities of Some Novel Carbocyclic Guanosine Analogues with a Cyclobutane Ring.

Cyclobutyl nucleoside analogues containing guanine and 8-azaguanine (compounds 5-10) were prepared from (1R,cis)-3-aminomethyl-2,2-dimethylcyclobutylmethanol (1). All were evaluated as antiviral and antitumoral agents in a variety of assay systems. Compounds 6 and 7 showed a noteworthy activity against a respiratory syncytial virus and compound 10 was moderately active against vaccinia virus. Only compound 5 showed some cytostatic activity.

Emerging anti-HIV drugs

There are now exactly 20 anti-HIV drugs licenced (approved) for clinical use, and > 30 anti-HIV compounds under (pre)clinical development. The licensed anti-HIV drugs fall into five categories: nucleoside reverse transcriptase inhibitors (NRTIs: zidovudine, didanosine, zalcitabine, stavudine, lamivudine, abacavir and emtricitabine); nucleotide reverse transcriptase inhibitors (NtRTIs: tenofovir disoproxil fumarate); non-nucleoside reverse transcriptase inhibitors (NNRTIs: nevirapine, delavirdine and efavirenz); protease inhibitors (PIs: saquinavir, indinavir, ritonavir, nelfinavir, amprenavir, lopinavir, atazanavir and fosamprenavir); and fusion inhibitors (FIs: enfuvirtide). The compounds that are currently under clinical (Phase I, II or III) or preclinical investigation are either targeted at the same specific viral proteins as the licensed compounds (i.e., reverse transcriptase [NRTIs: PSI-5004, (-)-dOTC, DPC-817, elvucitabine, alovudine, MIV-210, amdoxovir, DOT; NNRTIs: thiocarboxanilide, UC-781, capravirine, dapivirine, etravirine, rilpivirine], protease [PIs: tipranavir, TMC-114]) or other specific viral proteins (i.e., gp120: cyanovirin N; attachment inhibitors: AIs, such as BMS-488043; integrase: L-870,812, PDPV-165; capsid proteins: PA-457, alpha-HCG); or cellular proteins (CD4 downmodulators: CADAs; CXCR4 antagonists: AMD-070, CS-3955; CCR5 antagonists: TAK-220, SCH-D, AK-602, UK-427857). Combination therapy is likely to remain the gold standard for the treatment of AIDS so as to maximise potency, minimise toxicity and diminish the risk for resistance development. Ideally, pill burden should be reduced to once-daily dosing so as to optimise the patient's compliance and reduce the treatment costs.

Synthesis and stereochemical characterisation of platinum(II) complexes with the antiviral agents penciclovir and famciclovir

Design, synthesis and biological evaluation of novel acetamide-substituted doravirine and its prodrugs as potent HIV-1 NNRTIs

CCDC 671098: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.

Modeling of laser penetration in a powder bed during selective laser sintering of metal powders

Le Frittage Selectif par Laser (FSL) est un procede de prototypage rapide prometteur pour la fabrication d'objects 3D fonctionnels par frittage direct de poudres metalliques. Un modele analytique simple a ete developpe pour simuler l'absorption et la penetration de l'energie laser dans le FSL. Ce modele a ete utilise pour des melanges de poudres Fe-Cu et WC-Co, irradiees par lasers Nd-YAG ou CO 2 . Il permet d'evaluer la fraction d'energie totale absorbee et la penetration optique du faisceau laser dans les poudres et de donner une estimation des dimensions de la zone frittee. Les resultats de simulation aideront non seulement a avoir une meilleure connaissance des phenomenes physiques associes mais aussi a optimiser le procede FSL.

Advanced applications of coordinate measuring machines in CAD modeling and product inspection

No abstract is provided for this article.

Potent and selective anti-retrovirus activity of 9-(RS)-(3-fluoro-2-phosphonylmethoxypropyl) purine derivatives

Antiviral Activity of Triazine Analogues of 1-(<i>S</i>)-[3-Hydroxy-2-(phosphonomethoxy)propyl]cytosine (Cidofovir) and Related Compounds

Treatment of 5-azacytosine sodium salt with diisopropyl [(2-chloroethoxy)methyl]phosphonate followed by removal of ester groups with BrSi(CH3)3 afforded 1-[2-(phosphonomethoxy)ethyl]-5-azacytosine (3). Reaction of 5-azacytosine with [(trityloxy)methyl]-(2S)-oxirane followed by etherification with diisopropyl (bromomethyl)phosphonate and removal of ester groups gave 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]-5-azacytosine (1). The synthesis of 6-azacytosine congener 2 was analogous using N4-benzoylated intermediates. Compound 1 was shown to exert strong activity against a broad spectrum of DNA viruses including adenoviruses, poxviruses, and herpesviruses (i.e., herpes simplex viruses, varicella zoster virus, and human cytomegalovirus). Decomposition of 1 in alkaline solutions resulted in products 17 and 18. While the N-formylguanidine derivative 17 proved active, the carbamyolguanidine derivative 18 was devoid of antiviral activity.