title: Novel quinolinonyl diketo acid derivatives as HIV-1 integrase inhibitors: design, synthesis, and biological activities.
abstract: Novel quinolinonyl diketo acids were designed to obtain integrase (IN) inhibitors selectively active against the strand transfer (ST) step of the HIV integration process. Those new compounds are characterized by a single aryl diketo acid (DKA) chain in comparison to 4, a bifunctional diketo acid reported by our group as an anti-IN agent highly potent against both the 3'-processing and ST steps. Compound 6d was the most potent derivative in IN enzyme assays, while 6i showed the highest potency against HIV-1 in acutely infected cells. The selective inhibition of ST suggested the newly designed monofunctional DKAs bind the IN-DNA acceptor site without affecting the DNA donor site.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur, Fondazione Cenci BolognettiUniversità di Roma, La Sapienza, Roma, Italy. roberto.disanto@uniroma1.it
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
authors.forename: Roberta
authors.initials: R
authors.lastname: Costi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Roux
authors.forename: Gaetano
authors.initials: G
authors.lastname: Miele
authors.forename: Giuliana Cuzzucoli
authors.initials: GC
authors.lastname: Crucitti
authors.forename: Alberto
authors.initials: A
authors.lastname: Iacovo
authors.forename: Federica
authors.initials: F
authors.lastname: Rosi
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavecchia
authors.forename: Luciana
authors.initials: L
authors.lastname: Marinelli
authors.forename: Carmen
authors.initials: C
authors.lastname: Di Giovanni
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Lucia
authors.initials: L
authors.lastname: Palmisano
authors.forename: Mauro
authors.initials: M
authors.lastname: Andreotti
authors.forename: Roberta
authors.initials: R
authors.lastname: Amici
authors.forename: Clementina Maria
authors.initials: CM
authors.lastname: Galluzzo
authors.forename: Lucia
authors.initials: L
authors.lastname: Nencioni
authors.forename: Anna Teresa
authors.initials: AT
authors.lastname: Palamara
authors.forename: Yves
authors.initials: Y
authors.lastname: Pommier
authors.forename: Christophe
authors.initials: C
authors.lastname: Marchand
mesh_terms: D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015195:Drug Design; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007651:Keto Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000145:classification / Q000494:pharmacology*; D015394:Molecular Structure; D011804:Quinolines / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D019428:HIV Integrase Inhibitors; D007651:Keto Acids; D011804:Quinolines; C037219:quinoline