Novel isoquinoline derivatives as antimicrobial agents

被引：52

作者：

Galan, Abraham ^{[1
]}

Moreno, Laura ^{[1
]}

Parraga, Javier ^{[1
]}

Serrano, Angel ^{[1
]}

Jesus Sanz, Ma ^{[2
,3
]}

Cortes, Diego ^{[1
]}

Cabedo, Nuria ^{[4
]}

机构：

[1] Univ Valencia, Fac Farm, Dept Farmacol, Lab Farmacoquim, Valencia 46100, Spain

[2] Univ Valencia, Fac Med, Dept Farmacol, Valencia 46013, Spain

[3] Univ Clin Hosp Valencia, Inst Hlth Res INCLIVA, Valencia, Spain

[4] Univ Politecn Valencia, Ctr Ecol Quim Agr, Inst Agroforestal Mediterraneo, Valencia 46022, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 11期

关键词：

Esters and carbamates 1-alkyl-isoquinolines; Bactericide; Fungicide; ACTIVITIES IN-VITRO; ANTIFUNGAL; ANTIBACTERIAL; ANTIBIOTICS; INHIBITORS; ALKALOIDS;

D O I：

10.1016/j.bmc.2013.03.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：3221 / 3230

页数：10

共 19 条

[1] Tetrahydroisoquinolines acting as dopaminergic ligands. A molecular modeling study using MD simulations and QM calculations [J].

Andujar, Sebastian ;

Suvire, Fernando ;

Berenguer, Inmaculada ;

Cabedo, Nuria ;

Marin, Paloma ;

Moreno, Laura ;

Dolores Ivorra, Maria ;

Cortes, Diego ;

Enriz, Ricardo D. .

JOURNAL OF MOLECULAR MODELING, 2012, 18 (02) :419-431

[2] β-Phenylethylamines and the isoquinoline alkaloids [J].

Bentley, KW .

NATURAL PRODUCT REPORTS, 2005, 22 (02) :249-268

[3] Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice [J].

Berenguer, Inmaculada ;

El Aouad, Noureddine ;

Andujar, Sebastian ;

Romero, Vanessa ;

Suvire, Fernando ;

Freret, Thomas ;

Bermejo, Almudena ;

Dolores Ivorra, Maria ;

Enriz, Ricardo D. ;

Boulouard, Michel ;

Cabedo, Nuria ;

Cortes, Diego .

BIOORGANIC & MEDICINAL CHEMISTRY, 2009, 17 (14) :4968-4980

[4] Syntheses and antitumor targeting G1 phase of the cell cycle of benzoyldihydroisoquinolines and related 1-substituted isoquinolines [J].

Bermejo, A ;

Andreu, I ;

Suvire, F ;

Léonce, S ;

Caignard, DH ;

Renard, P ;

Pierré, A ;

Enriz, RD ;

Cortes, D ;

Cabedo, N .

JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (23) :5058-5068

[5]

Bermejo A., 1995, NAT PROD LETT, V6, P57, DOI [DOI 10.1080/10575639508044088., 10.1080/10575639508044088, DOI 10.1080/10575639508044088]

[6] BIOXALOMYCINS, NEW ANTIBIOTICS PRODUCED BY THE MARINE STREPTOMYCES SP LL-31F508 - TAXONOMY AND FERMENTATION [J].

BERNAN, VS ;

MONTENEGRO, DA ;

KORSHALLA, JD ;

MAIESE, WM ;

STEINBERG, DA ;

GREENSTEIN, M .

JOURNAL OF ANTIBIOTICS, 1994, 47 (12) :1417-1424

[7] Synthesis and dopamine receptor selectivity of the benzyltetrahydroisoquinoline, (R)-(+)-nor-roefractine [J].

Cabedo, N ;

Protais, P ;

Cassels, BK ;

Cortes, D .

JOURNAL OF NATURAL PRODUCTS, 1998, 61 (06) :709-712

[8] An Overview on Benzylisoquinoline Derivatives with Dopaminergic and Serotonergic Activities [J].

Cabedo, N. ;

Berenguer, I. ;

Figadere, B. ;

Cortes, D. .

CURRENT MEDICINAL CHEMISTRY, 2009, 16 (19) :2441-2467

[9] Enantioselective syntheses of dopaminergic (R)- and (S)-benzyltetrahydroisoquinolines [J].

Cabedo, N ;

Andreu, I ;

de Arellano, MCR ;

Chagraoui, A ;

Serrano, A ;

Bermejo, A ;

Protais, P ;

Cortes, D .

JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (11) :1794-1801

[10] KEY ANTIFUNGAL, ANTIBACTERIAL AND ANTIINSECT ASSAYS - A CRITICAL-REVIEW [J].

COLE, MD .

BIOCHEMICAL SYSTEMATICS AND ECOLOGY, 1994, 22 (08) :837-856

← 1 2 →