Mechanism of the antiviral activity of new aurintricarboxylic acid analogues

被引:14
作者
Reymen, D [1 ]
Witvrouw, M [1 ]
Este, JA [1 ]
Neyts, J [1 ]
Schols, D [1 ]
Andrei, G [1 ]
Snoeck, R [1 ]
Cushman, M [1 ]
Hejchman, E [1 ]
DeClercq, E [1 ]
机构
[1] PURDUE UNIV,SCH PHARM & PHARM SCI,DEPT MED CHEM & PHARMACOGNOSY,W LAFAYETTE,IN 47907
关键词
aurintricarboxylic acid; human herpesvirus type 6; human cytomegalovirus; human immunodeficiency virus type 1; glycoprotein gp120; CD4; receptor;
D O I
10.1177/095632029600700304
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Various new aurintricarboxylic acid (ATA) polymer analogues have been evaluated for their antiviral activity against a wide array of DNA and RNA viruses, and their mechanism of action against human cytomegalovirus (HCMV) and human immunodeficiency virus type 1 (HIV-1). Most of the polymers exhibited marked antiviral activity against a variety of enveloped viruses, but not against non-enveloped viruses, The ATA polymers displayed the most pronounced activity against HIV-1, HCMV and human herpesvirus type 6 (HHV-6), Their action against HCMV and HIV could be ascribed to inhibition of the initial attachment of virus particles to the cells, Using radiolabelled virus, we proved that the polymers inhibit the binding of HCMV to HEL fibroblasts, By flow cytometric analysis, we demonstrated that these new polymers interfere with (i) the binding of OKT4A monoclonal antibody (mAb) to the cellular CD4 receptor, (ii) the binding of anti-gp120 mAb to HIV-1 glycoprotein (gp) 120, and (iii) the adsorption of HIV-1 virions and recombinant HIV-1gp120 (rgp120) to MT-4 cells, The presence of a salicylic acid substituent on the central bridging carbon in the parent compound ATA seems to play an important role in the anti-HIV activity of these ATA related polymer analogues.
引用
收藏
页码:142 / 152
页数:11
相关论文
共 34 条
[1]   INHIBITORY EFFECT OF SELECTED ANTIVIRAL COMPOUNDS ON ARENAVIRUS REPLICATION INVITRO [J].
ANDREI, G ;
DECLERCQ, E .
ANTIVIRAL RESEARCH, 1990, 14 (4-5) :287-300
[2]   FUCHSIN ACID SELECTIVELY INHIBITS HUMAN IMMUNODEFICIENCY VIRUS (HIV) REPLICATION INVITRO [J].
BABA, M ;
SCHOLS, D ;
PAUWELS, R ;
BALZARINI, J ;
DECLERCQ, E .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1988, 155 (03) :1404-1411
[3]   AURINTRICARBOXYLIC ACID AND EVANS BLUE REPRESENT 2 DIFFERENT CLASSES OF ANIONIC COMPOUNDS WHICH SELECTIVELY INHIBIT THE CYTOPATHOGENICITY OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-III LYMPHADENOPATHY-ASSOCIATED VIRUS [J].
BALZARINI, J ;
MITSUYA, H ;
DECLERCQ, E ;
BRODER, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1986, 136 (01) :64-71
[4]  
Caro N., 1892, CHEM BER, V25, P939
[5]   DISSEMINATED HUMAN HERPESVIRUS-6 INFECTION IN AIDS [J].
CORBELLINO, M ;
LUSSO, P ;
GALLO, RC ;
PARRAVICINI, C ;
GALLI, M ;
MORONI, M .
LANCET, 1993, 342 (8881) :1242-1242
[6]   PREPARATION AND ANTI-HIV ACTIVITIES OF AURINTRICARBOXYLIC ACID FRACTIONS AND ANALOGS - DIRECT CORRELATION OF ANTIVIRAL POTENCY WITH MOLECULAR-WEIGHT [J].
CUSHMAN, M ;
WANG, PL ;
CHANG, SH ;
WILD, C ;
DECLERCQ, E ;
SCHOLS, D ;
GOLDMAN, ME ;
BOWEN, JA .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) :329-337
[7]   SYNTHESIS AND ANTI-HIV ACTIVITIES OF LOW-MOLECULAR-WEIGHT AURINTRICARBOXYLIC ACID FRAGMENTS AND RELATED-COMPOUNDS [J].
CUSHMAN, M ;
KANAMATHAREDDY, S ;
DECLERCQ, E ;
SCHOLS, D ;
GOLDMAN, ME ;
BOWEN, JA .
JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (01) :337-342
[8]   DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF COSALANE, A NOVEL ANTI-HIV AGENT WHICH INHIBITS MULTIPLE FEATURES OF VIRUS REPRODUCTION [J].
CUSHMAN, M ;
GOLEBIEWSKI, WM ;
MCMAHON, JB ;
BUCKHEIT, RW ;
CLANTON, DJ ;
WEISLOW, O ;
HAUGWITZ, RD ;
BADER, JP ;
GRAHAM, L ;
RICE, WG .
JOURNAL OF MEDICINAL CHEMISTRY, 1994, 37 (19) :3040-3050
[9]   SYNTHESIS OF THE COVALENT HYDRATE OF THE INCORRECTLY ASSUMED STRUCTURE OF AURINTRICARBOXYLIC ACID (ATA) [J].
CUSHMAN, M ;
KANAMATHAREDDY, S .
TETRAHEDRON, 1990, 46 (05) :1491-1498
[10]   ANTI-HIV AND ANTI-HCMV ACTIVITIES OF NEW AURINTRICARBOXYLIC ACID ANALOGS [J].
CUSHMAN, M ;
WANG, P ;
REYMEN, D ;
ESTE, J ;
WITVROUW, M ;
NEYTS, J ;
DECLERCQ, E .
ANTIVIRAL CHEMISTRY & CHEMOTHERAPY, 1995, 6 (03) :179-186