title: Novel isoquinoline derivatives as antimicrobial agents.
abstract: The wide variety of potent biological activities of natural and synthetic isoquinoline alkaloids encouraged us to develop novel antimicrobial isoquinoline compounds. We synthesized a variety of differently functionalized 1-pentyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines (THIQs), including dihydroisoquinolinium salts (2 and 5), methyl pentanoate-THIQ (6), 1-pentanol-THIQ (7), ester derivatives (8-15) and carbamate derivatives (16-23). We employed classic intramolecular Bischler-Napieralski cyclodehydration to generate the isoquinoline core. All the structures were characterized by nuclear magnetic resonance and mass spectrometry. The bactericide and fungicide activities were evaluated for all the synthesized compounds and structure-activity relationships were established. Many compounds exhibited high and broad-range bactericidal activity. Fluorophenylpropanoate ester 13 and the halogenated phenyl- (17, 18) and phenethyl carbamates (21, 22) exerted the most remarkable bactericidal activity. However, few compounds displayed antifungal activity against most of the fungi tested. Among them, chlorinated derivatives like chlorobenzoate and chlorophenylpropanoate esters (10 and 14, respectively) and chlorophenethyl carbamate 22, exhibited the greatest antifungal activity.
authors.affiliation: Departamento de Farmacología, Laboratorio de Farmacoquímica, Facultad de Farmacia, Universidad de Valencia, 46100 Burjassot, Valencia, Spain.
authors.forename: Abraham
authors.initials: A
authors.lastname: Galán
authors.forename: Laura
authors.initials: L
authors.lastname: Moreno
authors.forename: Javier
authors.initials: J
authors.lastname: Párraga
authors.forename: Ángel
authors.initials: Á
authors.lastname: Serrano
authors.forename: Ma Jesús
authors.initials: MJ
authors.lastname: Sanz
authors.forename: Diego
authors.initials: D
authors.lastname: Cortes
authors.forename: Nuria
authors.initials: N
authors.lastname: Cabedo
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000254:growth & development; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D007546:Isoquinolines