A novel H<sub>2</sub>S releasing-monastrol hybrid (MADTOH) inhibits L-type calcium channels

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

doi:10.1039/d0nj04415f

Cited by 5 publications

(4 citation statements)

References 46 publications

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“…This method utilizes the absorption band of MB (λ = 670 nm) generated from the reaction between the released H 2 S with N , N -dimethyl- p -phenylenediamine in the presence of FeCl 3 and acid for characterization. As illustrated in Figure S9, the concentration of H 2 S release from P2 was observed and reached a maximum value (2.47 μM) from P2 at 3.5 h, which was attributed to the hydrolysis of P2 in the aqueous solution (Figure b). ,− Additionally, the increased temperature is helpful in the H 2 S release, which was revealed by the increased H 2 S concentration (3.05 μM) detected from P2 when the testing temperature was increased to 45 °C. This phenomenon may be ascribed to the overflow of H 2 S gas molecules induced by aggravated thermal motion in aqueous solution and accelerated hydrolysis degree.…”

Section: Resultsmentioning

confidence: 89%

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy

Zhu

et al. 2022

ACS Appl. Mater. Interfaces

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Photothermal therapy (PTT) has emerged as a promising alternative or supplement to cancer treatments. While PTT induces the ablation of solid tumors, its efficiency is hampered by self-recovery within impaired cancer cells through glycolysis and respiration metabolism. Based on this, the introduction of hydrogen sulfide (H2S)-mediated respiration inhibition is a good choice to make up for the PTT limitation. Herein, nanovesicles (NP1) are integrated by a hypoxia-responsive conjugated polymer (P1), polymetric H2S donor (P2), and near-infrared (NIR) light-harvesting aza-BODIPY dye (B1) for the delivery of H2S and synergistic H2S gas therapy/PTT. The scaffold of NP1 undergoes disassembly in the hypoxic environments, thus triggering the hydrolysis of P2 to continuously long-term release H2S. Dependent on the superior photothermal ability of B1, NP1 elicits high photothermal conversion efficiency (η = 19.9%) under NIR light irradiation for PTT. Moreover, NP1 serves as in situ H2S bombers in the hypoxic tumor environment and suppresses the mitochondrial respiration through inhibiting expression of cytochrome c oxidase (COX IV) and cutting off the adenosine triphosphate (ATP) generation. Both in vitro and in vivo results demonstrate good antitumor efficacy of H2S gas therapy/PTT, which will be recommended as an advanced strategy for cancer therapeutics.

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Section: Resultsmentioning

confidence: 89%

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy

Zhu

et al. 2022

ACS Appl. Mater. Interfaces

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“…For the synthesis of the target derivatives, we have selected four clinically used antihistamines and have coupled them with two well-established H 2 S donors, namely, 4-hydroxythiobenzamide ( 1 , TBZ) and 5-(4-hydroxyphenyl)-3 H -1,2-dithiole-3-thione (ADT-OH, 2 ). The thione was prepared from trans -anethole using reported procedures …”

Section: Resultsmentioning

confidence: 99%

“…The thione was prepared from trans-anethole using reported procedures. 26 Thus, bilastine (3) was esterified with either 1 or 2 using N,N′-dicyclohexylcarbodiimide (DCC) in the presence of 4dimethylaminopyridine (DMAP) to yield the corresponding esters 4 and 5 (Scheme 1).…”

Section: ■ Resultsmentioning

confidence: 99%

Novel H₂S-Releasing Bifunctional Antihistamine Molecules with Improved Antipruritic and Reduced Sedative Actions

Antoniadou,

Georgiou,

Dotsikas

et al. 2023

J. Med. Chem.

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Hydrogen sulfide (H 2 S) is an endogenous gasotransmitter with anti-inflammatory actions that also reduces itching. To test whether a combination of an antihistamine with a H 2 S donor has improved antipruritic efficacy, bifunctional molecules with antihistamine and H 2 Sreleasing pharmacophores were synthesized and tested in vitro and in vivo. H 2 S release from the hybrid molecules was evaluated with the methylene blue and lead acetate methods, and H1-blocking activity was assessed by determining tissue factor expression inhibition. All new compounds released H 2 S in a dose-dependent manner and retained histamine blocking activity. Two compounds with the highest potency were evaluated in vivo for their antipruritic as well as sedative action; they proved to possess higher efficacy in inhibiting histamine-induced pruritus and decreased sedative effects compared to the parent compounds (hydroxyzine and cetirizine), suggesting that they exhibit superior antipruritic action and limited side effects that likely arise from the H 2 S-releasing moiety.

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“…Impressive drug synergism was observed with MADTOH, a monastrol-H 2 S-releasing hybrid, as increased inhibitory effects against L-type calcium channels were observed with this compound in comparison to both monastrol and ADT-OH alone [ 93 ]. L-type calcium channel blockers hold promise as an effective therapy for several cardiovascular disorders, including myocardial ischemia [ 94 ].…”

Section: H 2 S Donors That Protect Against Myocard...mentioning

confidence: 99%

H2S Donors with Cytoprotective Effects in Models of MI/R Injury and Chemotherapy-Induced Cardiotoxicity

Lukesh

2023

Antioxidants

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Hydrogen sulfide (H2S) is an endogenous signaling molecule that greatly influences several important (patho)physiological processes related to cardiovascular health and disease, including vasodilation, angiogenesis, inflammation, and cellular redox homeostasis. Consequently, H2S supplementation is an emerging area of interest, especially for the treatment of cardiovascular-related diseases. To fully unlock the medicinal properties of hydrogen sulfide, however, the development and refinement of H2S releasing compounds (or donors) are required to augment its bioavailability and to better mimic its natural enzymatic production. Categorizing donors by the biological stimulus that triggers their H2S release, this review highlights the fundamental chemistry and releasing mechanisms of a range of H2S donors that have exhibited promising protective effects in models of myocardial ischemia-reperfusion (MI/R) injury and cancer chemotherapy-induced cardiotoxicity, specifically. Thus, in addition to serving as important investigative tools that further advance our knowledge and understanding of H2S chemical biology, the compounds highlighted in this review have the potential to serve as vital therapeutic agents for the treatment (or prevention) of various cardiomyopathies.

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

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.

Cited by 5 publications

References 46 publications

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy

Novel H₂S-Releasing Bifunctional Antihistamine Molecules with Improved Antipruritic and Reduced Sedative Actions

H2S Donors with Cytoprotective Effects in Models of MI/R Injury and Chemotherapy-Induced Cardiotoxicity

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

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.

Cited by 5 publications

References 46 publications

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy

Hypoxia-Activatable Nanovesicles as In Situ Bombers for Combined Hydrogen-Sulfide-Mediated Respiration Inhibition and Photothermal Therapy

Novel H2S-Releasing Bifunctional Antihistamine Molecules with Improved Antipruritic and Reduced Sedative Actions

H2S Donors with Cytoprotective Effects in Models of MI/R Injury and Chemotherapy-Induced Cardiotoxicity

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

Novel H₂S-Releasing Bifunctional Antihistamine Molecules with Improved Antipruritic and Reduced Sedative Actions