title: Synthesis and biological evaluation of (acyl)hydrazones and thiosemicarbazones obtained via in situ condensation of iminium salts with nitrogen-containing nucleophiles.
abstract: An unprecedented, highly convergent, high-yielding, one-pot synthesis of (acyl)hydrazones and thiosemicarbazones was carried out by the in situ condensation of isolable iminium chlorides of imidazolidin-2-(thio)one, tetrahydropyrimidin-2-thione and indole derivatives with nitrogen nucleophiles in the presence of a base. The developed reaction procedure is largely advantageous. It is highly parallelizable, no intermediates need to be isolated and minimal sample handling is required during the purification steps. Some relevant reaction parameters including reaction temperature and p[Formula: see text] of the base are discussed. NMR analysis was carried out to assess the stereochemistry of the obtained compounds. The stereochemical outcome of the reaction was found to be affected by the nature of the nitrogen-containing nucleophile being the majority of the derivatives isolated as single geometric isomers. The cytotoxicity and antiviral activities of the prepared compounds have been preliminary assessed. In cell-based screenings some of the derivatives proved to be cytotoxic at low micromolar concentrations and interesting anti-Reo-1 properties have been detected.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV 3, 16132, Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Caneva
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV 3, 16132, Genova, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Alfei
authors.affiliation: Department of Chemistry and Pharmacy, Emil Fischer Center, Friedrich-Alexander University, Schuhstraße 19, 91052, Erlangen, Germany.
authors.forename: Monica
authors.initials: M
authors.lastname: De Maria
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, s.p.8, Km 0.700, 09042, Monserrato, Cagliari, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ibba
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, s.p.8, Km 0.700, 09042, Monserrato, Cagliari, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Delogu
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV 3, 16132, Genova, Italy. andrea.spallarossa@unige.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Spallarossa
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria di Monserrato, s.p.8, Km 0.700, 09042, Monserrato, Cagliari, Italy. rloddo@unica.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003603:Cytotoxins / Q000138:chemical synthesis / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry; D012492:Salts; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D003603:Cytotoxins; D006835:Hydrazones; D012492:Salts; D013882:Thiosemicarbazones; D009584:Nitrogen
keywords: (Acyl )hydrazones; Cytotoxic and antiviral activities; Iminium salts; Indole derivatives; Thiosemicarbazones; Thioureas