Eva Rivero-Buceta1, Paula Carrero2, Elena Casanova3, Elisa G Doyagüez4, Andrés Madrona1, Ernesto Quesada1, María Jesús Peréz-Pérez1, Raquel Mateos5, Laura Bravo5, Leen Mathys6, Sam Noppen6, Evgeny Kiselev7, Christophe Marchand7, Yves Pommier7, Sandra Liekens6, Jan Balzarini6, María José Camarasa1, Ana San-Félix8. 1. Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. 2. Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; ABG Patentes, Avenida de Burgos 16D, 28036 Madrid, Spain. 3. Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; Euroquímica S.A., Crta. Yeles, Km 2, Illescas, Toledo, Spain. 4. Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain; Centro de Química Orgánica "Lora-Tamayo" (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. 5. Instituto de Ciencia y Tecnología de Alimentos y Nutrición (ICTAN-CSIC), Jose Antonio Novais 10, 28040 Madrid, Spain. 6. Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium. 7. Developmental Therapeutics Branch and Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States. 8. Instituto de Química Médica (IQM-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. Electronic address: anarosa@iqm.csic.es.
Abstract
The glycoprotein gp120 of the HIV-1 viral envelope has a high content in mannose residues, particularly α-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5-triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes α-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1.
The glycoprotein gp120 of the n class="Species">HIV-1 viral envelope has a high content in mannose residues, particularly α-1,2-mannose oligomers. Compounds that interact with these high-mannose type glycans may disturb the interaction between gp120 and its (co)receptors and are considered potential anti-HIV agents. Previously, we demonstrated that a tripodal receptor (1), with a central scaffold of 1,3,5-triethylbenzene substituted with three 2,3,4-trihydroxybenzoyl groups, selectively recognizes α-1,2-mannose polysaccharides. Here we present additional studies to determine the anti-HIV-1 activity and the mechanism of antiviral activity of this compound. Our studies indicate that 1 shows anti-HIV-1 activity in the low micromolar range and has pronounced gp120 binding and HIV-1 integrase inhibitory capacity. However, gp120 binding rather than integrase inhibition seems to be the primary mechanism of antiviral activity of 1.
Authors: C O R Junior; S C Verde; C A M Rezende; W Caneschi; M R C Couri; B R McDougall; W E Robinson; M V de Almeida Journal: Curr Med Chem Date: 2013 Impact factor: 4.530