title: Synthesis and antiviral activity of new phenylimidazopyridines and N-benzylidenequinolinamines derived by molecular simplification of phenylimidazo[4,5-g]quinolines.
abstract: Continuing our program of research concerning the antiviral activity of a wide series of new angular and linear azolo bicyclic and tricyclic derivatives, now we have simplified and modified the 4-chloro-2-(4-nitrophenyl)-3H-imidazo[4,5-g]quinoline 1, which previously resulted the most active derivative, through either the elimination of the central ring or the opening of the imidazole ring, obtaining various imidazopyridines and N-benzylidenequinolinamines respectively. Title compounds were tested in cell-based assays for cytotoxicity and antiviral activity against representatives of two DNA virus families as wells as against representatives of RNA virus families containing single-stranded, either positive-sense (ssRNA(+)) or negative-sense (ssRNA(-)), and double-stranded genomes (dsRNA). Some imidazo[4,5-b]pyridines emerged as new derivatives endowed with antiviral activity against Vaccinia Virus (VV) at concentrations ranging from 2 to 16 μM. In particular, compound 2b demonstrate to be about 10 times more potent than Cidofovir, used as reference drug. Similarly, the imidazo[4,5-c]pyridines and N-benzylidenequinolinamines derivatives resulted active against Bovine Viral Diarrhoea virus (BVDV), at concentrations ranging from 1.2 to 28 μM. Above all compounds 1, 3a and 3f showed an EC50 of the same order of magnitude of the reference drug, the 2'-C-methyl-guanosine. Moreover, several N-benzylidenequinolinamines showed an interesting activity against Respiratory Syncytial Virus (RSV) at concentrations between 12 and 26 μM.
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria s.p.8, Km 0,700, 09042 Monserrato, Ca, Italy. Electronic address: rloddo@unica.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Loddo
authors.affiliation: Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Briguglio
authors.affiliation: Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Corona
authors.affiliation: Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Sandra
authors.initials: S
authors.lastname: Piras
authors.affiliation: Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Loriga
authors.affiliation: Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Paglietti
authors.affiliation: Dipartimento di Chimica e Farmacia, Università degli Studi di Sassari, Via Muroni 23/A, 07100 Sassari, Italy. Electronic address: acarta@uniss.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Carta
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria s.p.8, Km 0,700, 09042 Monserrato, Ca, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sanna
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria s.p.8, Km 0,700, 09042 Monserrato, Ca, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Giliberti
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria s.p.8, Km 0,700, 09042 Monserrato, Ca, 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 s.p.8, Km 0,700, 09042 Monserrato, Ca, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Farci
authors.affiliation: Dipartimento di Scienze Biomediche, Sezione di Microbiologia e Virologia, Università degli Studi di Cagliari, Cittadella Universitaria s.p.8, Km 0,700, 09042 Monserrato, Ca, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: La Colla
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004267:DNA Viruses / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012328:RNA Viruses / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D000998:Antiviral Agents; D007093:Imidazoles; D011725:Pyridines
keywords: Antiviral activity; Bovine viral diarrhoea virus (BVDV); Coxsackie virus type B5 (CVB-5); Herpes simplex virus type 1 (HSV-1); N-benzylidenequinolinamines; Phenylimidazopiridines; Respiratory syncytial virus (RSV); Vaccinia virus (VV)