title: Ruthenium arene complexes as HIV-1 integrase strand transfer inhibitors.
abstract: The quinolone HL(1) and the hydroxypyrimidine-carboxamide HL(2) were designed and synthesized as models of the HIV integrase strand transfer inhibitors Elvitegravir and Raltegravir (brand name Isentress), with the aim to study their complexing behavior and their biological activity. The Ru(arene) complexes [RuCl(η(6)-p-cym)L(1)], [RuCl(η(6)-p-cym)L(2)] and [RuCl(hexamethylbenzene)L(2)] were also synthesized and spectroscopically characterized and their X-ray diffraction structures were discussed. The ligands and the complexes showed inhibition potency in the sub/low-micromolar concentration range in anti-HIV-1 integrase enzymatic assays, with selectivity toward strand transfer catalytic process, without any significant cytotoxicity on cancer cells.
authors.affiliation: Dipartimento di Chimica, Università di Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy. mauro.carcelli@unipr.it
authors.forename: Mauro
authors.initials: M
authors.lastname: Carcelli
authors.forename: Alessia
authors.initials: A
authors.lastname: Bacchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Pelagatti
authors.forename: Gabriele
authors.initials: G
authors.lastname: Rispoli
authors.forename: Dominga
authors.initials: D
authors.lastname: Rogolino
authors.forename: Tino W
authors.initials: TW
authors.lastname: Sanchez
authors.forename: Mario
authors.initials: M
authors.lastname: Sechi
authors.forename: Nouri
authors.initials: N
authors.lastname: Neamati
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000737:chemistry; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry; D015363:Quinolones / Q000737:chemistry; D000068898:Raltegravir Potassium; D012428:Ruthenium
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D009942:Organometallic Compounds; D011760:Pyrrolidinones; D015363:Quinolones; D000068898:Raltegravir Potassium; C509700:elvitegravir; D012428:Ruthenium; D019427:HIV Integrase