Publications

The 2-phenyl-benzoxazin-4-ones were condensed with primary amine to form the 2,3-disubstituted quinazolin-4(3H)-ones. Their chemical structure was elucidated by means of spectral (FT-IR, 1H-NMR, MS) and elemental analysis. The antiviral activity and cytotoxicity of the compounds were tested in HeLa cells (vesicular stomatitis virus, Coxsackie virus B4 and respiratory syncytial virus), HEL cells [herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), vaccinia virus], Vero cells (parainfluenza-3, reovirus-1, Sindbis virus, Coxsackie virus B4 and Punta Toro virus). Among the new derivatives evaluated, specific antiviral activity was noted with compound QAA against vaccinia virus, parainfluenza-3 virus and Punta Toro virus, compound QOPD against HSV-1, HSV-2 and vaccinia virus, and compounds QONA and PD-NFIN against Coxsackie virus B4.   Key words:  Quinazoline, antiviral, HSV, vaccinia, sulphanamides.

The mechanisms of human immunodeficiency virus (HIV) infection of a man (VH) homozygous for the CCR5Delta32 mutation were investigated, and coreceptors other than CCR5 used by HIV type 1 (HIV-1) isolated from this individual were identified. In contrast to previous reports, this individual's rate of disease progression was not accelerated. Homozygosity for CCR5Delta32 mutation was demonstrated by PCR and DNA sequencing (R. Biti et al., Nat. Med. 3:252-253, 1997). CCR5 surface expression was absent on T lymphocytes and macrophages. HIV was isolated by coculture with peripheral blood mononuclear cells (PBMCs) from siblings who were homozygous (VM) or wild type (WT) for the CCR5Delta32 mutation. The virus demonstrated dual tropism for infection of MT2 cell line and primary macrophages. Sequencing of the full HIV genome directly from the patient's PBMCs revealed 21 nucleotide insertions in the V1 region of gp120. The VH envelope sequence segregated apart from both the T-cell-line-adapted tropic strains NL4-3 and SF2 and M-tropic strain JRFL or YU2 by phylogenetic tree analysis. VH was shown to utilize predominantly CXCR4 for entry into T lymphocytes and macrophages by HOS.CD4 cell infection assay, direct envelope protein fusion, and inhibition by anti-CXCR4 monoclonal antibody (12G5), SDF-1, and AMD3100. Microsatellite mapping demonstrated the separate inheritance of CXCR4 by both homozygote brothers (VH and VM). Our study demonstrates the ability of certain strains of HIV to readily use CXCR4 for infection or entry into macrophages, which is highly relevant to the pathogenesis of late-stage disease and presumably also HIV transmission.

Abstract Acyclic nucleotide analogs derived from antiviral 9-(2-phosphonylmethoxyethyl)adenine by modification at the side chain or by alternation of the heterocyclic base were synthesized and investigated for their antiviral activity.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Adamantanopyrrolidines 8, 9 and 10, adamantanopyrrolidines 16 and 18, adamantanoxazolone 20, adamantanopyrazolone 23, adamantanopyrazolothione 24 and adamantanocyclopentanamine 32 were synthesized and tested for anti-influenza A virus and trypanocidal activity. The stereoelectronic requirements for optimal antiviral and trypanocidal potency were investigated. Pyrrolidine 16 proved to be the most active of the compounds tested against influenza A virus, being 4-fold more active than amantadine, equipotent to rimantadine and 19-fold more potent than ribavirin. Oxazolone 20 showed significant trypanocidal activity against bloodstream forms of the African trypanosome, Trypanosoma brucei, being approximately 3 times more potent than rimantadine and almost 50-fold more active than amantadine.

HBV RNA at week 12 is an effective monitor of HBeAg seroconversion in HBeAg-positive patients treated with pegylated interferons.