title: Multivalent agents containing 1-substituted 2,3,4-trihydroxyphenyl moieties as novel synthetic polyphenols directed against HIV-1.
abstract: The synthesis and the assessment of the anti-HIV activity of a set of molecules inspired by the multivalent structures of some naturally-occurring polyphenols (tannins) are reported. Different multibranched scaffolds have been derived from pentaerythritol as the central core which distribute spatially synthetic polyphenolic subunits based on 1-substituted 2,3,4-trihydroxyphenyl moieties. A tetrapodal compound () bearing four N-(2,3,4-trihydroxyphenyl)amide groups, exhibits remarkable selective activity against HIV-1 with EC50 values in the micromolar scale, in the same range as those reported for the most representative anti-HIV tannins. Preliminary SAR studies emphasize the importance of the 1-substituted 2,3,4-trihydroxyphenyl moiety, the presence of an amide as the linker and the multivalent architecture of these molecules, since the anti-HIV activity increases with the number of polyphenolic moieties. The data support the interest in synthetic polyphenols and represent a promising starting point for further design and development of selective HIV-1 inhibitors.
authors.affiliation: Instituto de Química Médica CSIC, Juan de la Cierva 3, 28006 Madrid, Spain. EQ1@iqm.csic.es.
authors.forename: Aida
authors.initials: A
authors.lastname: Flores
authors.forename: María José
authors.initials: MJ
authors.lastname: Camarasa
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pérez-Pérez
authors.forename: Ana
authors.initials: A
authors.lastname: San-Félix
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Ernesto
authors.initials: E
authors.lastname: Quesada
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology / Q000821:virology; D002460:Cell Line; D015195:Drug Design; D015497:HIV-1 / Q000187:drug effects* / Q000254:growth & development; D015498:HIV-2 / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D059808:Polyphenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011409:Propylene Glycols / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013634:Tannins / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D059808:Polyphenols; D011409:Propylene Glycols; D013634:Tannins; C008783:pentaerythritol