A novel H2S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels

Taniris Cafiero Braga; Itamar Couto Guedes de Jesus; Kathleen Viveiros Soares; Silvia Guatimosim; Leonardo da Silva Neto; Cristiane Jovelina da-Silva; Luzia Valentina Modolo; José Evaldo Rodrigues Menezes Filho; Paula Rhana; Jader Santos Cruz; Ângelo de Fátima

doi:10.1039/D0NJ04415F

A novel H₂S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels†

Taniris Cafiero Braga,^a Itamar Couto Guedes de Jesus,^b Kathleen Viveiros Soares,^a Silvia Guatimosim,^b Leonardo da Silva Neto,^c Cristiane Jovelina da-Silva,^d Luzia Valentina Modolo,^d José Evaldo Rodrigues Menezes Filho,^e Paula Rhana,^f Jader Santos Cruz^f and Ângelo de Fátima

*^a

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* Corresponding authors

^a Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
E-mail: adefatima@qui.ufmg.br
Tel: +55-31-3409-6373

^b Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

^c Instituto Federal Farroupilha, Alegrete, RS, Brazil

^d Departamento de Botânica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

^e Faculdades Integradas de Sergipe, Tobias Barreto, SE, Brazil

^f Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Abstract

A new alleged monastrol-H₂S releasing hybrid, named MADTOH, was designed based on the structure of monastrol (M) and 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADTOH) and synthesized in 7.8% overall yield. MADTOH was shown to be an H₂S donor under physiological conditions. In addition, the hybrid causes a decrease in global calcium transient in cardiomyocytes similar to nifedipine (NIFE), taken as a positive control. Whole-cell voltage-clamp showed that MADTOH decreases L-type Ca²⁺ current in isolated ventricular cardiomyocytes.

New Journal of Chemistry

A novel H₂S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels†

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A novel H₂S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels

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