Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.
Molecular modeling studies and an updated highly predictive 3-D QSAR model led to the discovery of exceptionally potent indolyl aryl sulfones (IASs) characterized by the presence of either a pyrrolidyn-2-one nucleus at the indole-2-carboxamide or some substituents at the indole-2-carbohydrazide. Compounds 7 and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166 cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.
Ragno
Rino
R
Dipartimento di Studi Farmaceutici, Istituto Pasteur-Fondazione Cenci Bolognetti, Università di Roma La Sapienza, Piazzale Aldo Moro 5, I-00185 Roma, Italy. rino.ragno@uniroma1.it
Coluccia
Antonio
A
La Regina
Giuseppe
G
De Martino
Gabriella
G
Piscitelli
Francesco
F
Lavecchia
Antonio
A
Novellino
Ettore
E
Bergamini
Alberto
A
Ciaprini
Chiara
C
Sinistro
Anna
A
Maga
Giovanni
G
Crespan
Emanuele
E
Artico
Marino
M
Silvestri
Romano
R
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D015195:Drug Design; D024882:Drug Resistance, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000821:virology; D008264:Macrophages / Q000187:drug effects / Q000821:virology; D008958:Models, Molecular; D011760:Pyrrolidinones / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D012995:Solubility; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D019380:Anti-HIV Agents; D007211:Indoles; D011760:Pyrrolidinones; D013450:Sulfones