Searching for new antiarrhythmic agents: Evaluation of meta-hydroxymexiletine enantiomers

Catalano, Alessia; Budriesi, Roberta; Bruno, Claudio; Mola, Antonia Di; Defrenza, Ivana; Cavalluzzi, Maria Maddalena; Micucci, Matteo; Carocci, Alessia; Franchini, Carlo; Lentini, Giovanni

doi:10.1016/j.ejmech.2013.05.008

Cited by 18 publications

(14 citation statements)

References 36 publications

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“…At the dose of 50 mg/kg ip, only compound 1e showed a significant impairment of mouse motor coordination, with a slight increase in the number of falls being displayed. Since mexiletine is known to undergo extensive first-pass oxidative metabolism [16,26,27] that is linked to the generation of reactive species metabolites and/or cellular oxidative stress, the cytotoxicity of the four analogues was assessed using the MTT cell viability assay [28]. When the human hepatocellular liver carcinoma cells (HepG2) were challenged with the four mexiletine analogues at two concentrations (the first close to their corresponding EC 50 values, and the second 10-fold higher than the former), no cytotoxicity was observed (data not shown).…”

Section: Biological Resultsmentioning

confidence: 99%

Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues

Roselli

Carocci

Budriesi

et al. 2016

European Journal of Medicinal Chemistry

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Four mexiletine analogues have been tested for their antiarrhythmic, inotropic, and chronotropic effects on isolated guinea pig heart tissues and to assess calcium antagonist activity, in comparison with the parent compound mexiletine. All analogues showed from moderate to high antiarrhythmic activity. In particular, three of them (1b,c,e) were more active and potent than the reference drug, while exhibiting only modest or no negative inotropic and chronotropic effects and vasorelaxant activity, thus showing high selectivity of action. All compounds showed no cytotoxicity and 1b,c,d did not impair motor coordination. All in, these new analogues exhibit an interesting cardiovascular profile and deserve further investigation.

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Section: Biological Resultsmentioning

confidence: 99%

Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues

Roselli

Carocci

Budriesi

et al. 2016

European Journal of Medicinal Chemistry

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“…Both the prevention of ventricular tachycardia and the tonic block of the skeletal muscle channel effects exerted by ( R )‐mexiletine were higher than those displayed by its enantiomer , . At the same time, the ( S )‐isomer of mexiletine is more effective than the ( R )‐isomer in the treatment of allodynia .…”

Section: Using Direct Methods To Obtain Single Enantiomer Apismentioning

confidence: 99%

Stereoselective Crystallization as a Basis for Single‐Enantiomer Drug Production

Бредихин

Бредихина

2017

Chem Eng & Technol

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In the 21st century, single enantiomeric chiral active pharmaceutical ingredients (APIs) prevail among new drugs. Their preparation is made easier by using direct methods for the separation of racemates. The history of this issue is summarized and information about new and updated methods of conglomerate identification and practical implementation options for direct resolutions is provided. Examples are given for the application of direct methods for obtaining enantiopure APIs by the resolution of their racemic synthetic precursors, using a slight modification of the target product and finally by direct resolution of the racemic chiral drugs as such.

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“…Elemental analyses were performed on a Eurovector Euro EA 3000 analyzer. Chromatographic separations were performed on silica gel columns by column chromatography on silica gel (Kieselgel 60, 0.040–0.063 mm, Merck, Darmstadt, Germany) as previously described . TLC analyses were performed on precoated silica gel on aluminum sheets (Kieselgel 60 F 254 , Merck).…”

Section: Methodsmentioning

confidence: 99%

1,3-Benzothiazoles as Antimicrobial Agents

Defrenza

Catalano

Carocci

et al. 2014

J. Heterocyclic Chem.

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Starting from 2‐amino‐1,3‐mercaptobenzothiazoles recently reported (1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h), a series of the corresponding 2‐mercapto‐1,3‐benzothiazole isosters (2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h) were screened for their in vitro antibacterial and antifungal activities. Results underline that the presence of the mercapto moiety at the 2‐position of the heterocyclic nucleus is crucial for activity against bacteria. The biological screening against Candida spp. identified commercial 2f as the most promising compound as antifungal against Candida albicans and tropicalis. Molecular modeling studies supported these results. Then, to enlarge structure‐activity relationship (SAR) studies on series 1, newly synthesized compounds (1k, 1l, 1m, 1n, 1o, 1p) were reported. All the compounds belonging to this series and bearing a bulky substituent at the 6‐position of the aryl moiety showed high antifungal activity.

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Searching for new antiarrhythmic agents: Evaluation of meta-hydroxymexiletine enantiomers

Cited by 18 publications

References 36 publications

Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues

Synthesis, antiarrhythmic activity, and toxicological evaluation of mexiletine analogues

Stereoselective Crystallization as a Basis for Single‐Enantiomer Drug Production

1,3-Benzothiazoles as Antimicrobial Agents

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