1. Practical synthesis and elaboration of methyl 7-chloroindole-4-carboxylate
Phil B Alper, KhanhLinh T Nguyen J Org Chem. 2003 Mar 7;68(5):2051-3. doi: 10.1021/jo026434p.
A synthesis of a previously unknown indole derivative is presented. The route reported herein allows for the preparation of multihundred gram quantities of material without any chromatographic purification. Conditions are presented for the Pd-catalyzed elaboration of one of the "diversity generating elements" of this important pharmacophore.
2. Antibacterial and Antibiofilm Activities of Chloroindoles Against Vibrio parahaemolyticus
Ezhaveni Sathiyamoorthi, Olajide Sunday Faleye, Jin-Hyung Lee, Vinit Raj, Jintae Lee Front Microbiol. 2021 Aug 2;12:714371. doi: 10.3389/fmicb.2021.714371. eCollection 2021.
Vibrio parahaemolyticus is a food-borne pathogen recognized as the prominent cause of seafood-borne gastroenteritis globally, necessitating novel therapeutic strategies. This study examined the antimicrobial and antivirulence properties of indole and 16 halogenated indoles on V. parahaemolyticus. Among them, 4-chloroindole, 7-chloroindole, 4-iodoindole, and 7-iodoindole effectively inhibited planktonic cell growth, biofilm formation, bacterial motility, fimbrial activity, hydrophobicity, protease activity, and indole production. Specifically, 4-chloroindole at 20 μg/mL inhibited more than 80% of biofilm formation with a minimum inhibitory concentration (MIC) of 50 μg/mL against V. parahaemolyticus and Vibrio harveyi. In contrast, 7-chloroindole inhibited biofilm formation without affecting planktonic cell growth with a MIC of 200 μg/mL. Both chlorinated indoles caused visible damage to the cell membrane, and 4-chloroindole at 100 μg/mL had a bactericidal effect on V. parahaemolyticus within 30 min treatment, which is superior to the effect of tetracycline at the same dose. The quantitative structure-activity relationship (QSAR) analyses revealed that chloro and bromo at positions 4 or 5 of the indole are essential for eradicating the growth of V. parahaemolyticus. These results suggest that halogenated indoles have potential use in antimicrobial and antivirulence strategies against Vibrio species.
3. Biotransformation of chloro-substituted indoles to indigoids by phenol hydroxylase from Arthrobacter sp. W1
Shengnan Shi, Fang Ma, Tieheng Sun, Ang Li, Jiti Zhou, Yuanyuan Qu Appl Biochem Biotechnol. 2013 Jun;170(4):951-61. doi: 10.1007/s12010-013-0234-y. Epub 2013 Apr 30.
Recombinant Escherichia coli cells expressing phenol hydroxylase (designated as strain PH(IND)) were used to synthesize chloro-substituted indigoids by the transformation of indoles. The optimal conditions for the biotransformation of 4- and 7-chloroindole were determined by response surface methodology. Biotransformation kinetic assays revealed that strain PH(IND) showed high catalytic efficiency for 4- and 7-chloroindole. The formation rate of 7,7'-dichloroindigo (1.35 unit/mg cell dry weight) by strain PH(IND) was 1.14-fold higher than that of 4,4'-dichloroindigo. The intermediates of 7-chloroindole biotransformation were identified by high-performance liquid chromatography-mass spectroscopy, and the biotransformation mechanism was also proposed. These results suggested that there was a potential application of strain PH(IND) in the biotransformation of chloro-substituted indoles to valuable indigoids.
