Esterase-Triggered Self-Immolative Thiocarbamates Provide Insights into COS Cytotoxicity

Overview

Journal ACS Chem Biol

Publisher American Chemical Society

Specialties Biochemistry
Biology

Date 2019 Jan 15

PMID 30640440

Citations 17

Authors

Carolyn M Levinn

Andrea K Steiger

Michael D Pluth

Affiliations

Soon will be listed here.

Abstract

Hydrogen sulfide (HS) is an important gasotransmitter and biomolecule, and many synthetic small-molecule HS donors have been developed for HS-related research. One important class of triggerable HS donors is self-immolative thiocarbamates, which function by releasing carbonyl sulfide (COS), which is rapidly converted to HS by the ubiquitous enzyme carbonic anhydrase (CA). Prior studies of esterase-triggered thiocarbamate donors reported significant inhibition of mitochondrial bioenergetics and toxicity when compared to direct sulfide donors, suggesting that COS may function differently than HS. Here, we report a suite of modular esterase-triggered self-immolative COS donors and include the synthesis, HS release profiles, and cytotoxicity of the developed donors. We demonstrate that the rate of ester hydrolysis correlates directly with the observed cytotoxicity in cell culture, which further supports the hypothesis that COS functions as more than a simple HS shuttle in certain biological systems.

Citing Articles

Exploring the Reactivity of Electrophilic Organic Carbonates and Thiocarbonates as Vehicles to Convert Hydrosulfide into COS and CS.

Wade Wolfe M, Pines J, Sosa A, Pluth M J Org Chem. 2024; 89(21):16004-16009.

PMID: 39404704 PMC: 11700781. DOI: 10.1021/acs.joc.4c01690.

Fluorescent Probe as Dual-Organelle Localizer Through Differential Proton Gradients Between Lipid Droplets and Mitochondria.

Hernandez-Juarez C, Calahorra M, Pena A, Jimenez-Sanchez A Anal Chem. 2024; 96(22):9262-9269.

PMID: 38760019 PMC: 11154735. DOI: 10.1021/acs.analchem.4c01703.

Subcellular Delivery of Hydrogen Sulfide Using Small Molecule Donors Impacts Organelle Stress.

Gilbert A, Pluth M J Am Chem Soc. 2022; 144(38):17651-17660.

PMID: 36121306 PMC: 9896967. DOI: 10.1021/jacs.2c07225.

Thiol-Activated 1,2,4-Thiadiazolidin-3,5-diones Release Hydrogen Sulfide through a Carbonyl-Sulfide-Dependent Pathway.

Smith H, Pluth M J Org Chem. 2022; 87(18):12441-12446.

PMID: 36070356 PMC: 9893878. DOI: 10.1021/acs.joc.2c01220.

Moving Past Quinone-Methides: Recent Advances Toward Minimizing Electrophilic Byproducts from COS/HS Donors.

Pluth M Curr Top Med Chem. 2021; 21(32):2882-2889.

PMID: 34161211 PMC: 9179098. DOI: 10.2174/1568026621666210622130002.

References

Kamboures M, Blake D, Cooper D, Newcomb R, Barker M, Larson J . Breath sulfides and pulmonary function in cystic fibrosis. Proc Natl Acad Sci U S A. 2005; 102(44):15762-7. PMC: 1276081. DOI: 10.1073/pnas.0507263102. View

Studer S, Orens J, Rosas I, Krishnan J, Cope K, Yang S . Patterns and significance of exhaled-breath biomarkers in lung transplant recipients with acute allograft rejection. J Heart Lung Transplant. 2001; 20(11):1158-66. DOI: 10.1016/s1053-2498(01)00343-6. View

Steiger A, Zhao Y, Pluth M . Emerging Roles of Carbonyl Sulfide in Chemical Biology: Sulfide Transporter or Gasotransmitter?. Antioxid Redox Signal. 2017; 28(16):1516-1532. PMC: 5930797. DOI: 10.1089/ars.2017.7119. View

Abe K, Kimura H . The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci. 1996; 16(3):1066-71. PMC: 6578817. View

Steiger A, Pardue S, Kevil C, Pluth M . Self-Immolative Thiocarbamates Provide Access to Triggered H2S Donors and Analyte Replacement Fluorescent Probes. J Am Chem Soc. 2016; 138(23):7256-9. PMC: 4911618. DOI: 10.1021/jacs.6b03780. View

Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T . Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012; 9(7):676-82. PMC: 3855844. DOI: 10.1038/nmeth.2019. View

Tian L, Yang Y, Wysocki L, Arnold A, Hu A, Ravichandran B . Selective esterase-ester pair for targeting small molecules with cellular specificity. Proc Natl Acad Sci U S A. 2012; 109(13):4756-61. PMC: 3323987. DOI: 10.1073/pnas.1111943109. View

Haritos V, Dojchinov G . Carbonic anhydrase metabolism is a key factor in the toxicity of CO2 and COS but not CS2 toward the flour beetle Tribolium castaneum [Coleoptera: Tenebrionidae]. Comp Biochem Physiol C Toxicol Pharmacol. 2005; 140(1):139-47. DOI: 10.1016/j.cca.2005.01.012. View

Steiger A, Marcatti M, Szabo C, Szczesny B, Pluth M . Inhibition of Mitochondrial Bioenergetics by Esterase-Triggered COS/HS Donors. ACS Chem Biol. 2017; 12(8):2117-2123. PMC: 6022832. DOI: 10.1021/acschembio.7b00279. View

10.

Lin V, Lippert A, Chang C . Cell-trappable fluorescent probes for endogenous hydrogen sulfide signaling and imaging H2O2-dependent H2S production. Proc Natl Acad Sci U S A. 2013; 110(18):7131-5. PMC: 3645565. DOI: 10.1073/pnas.1302193110. View

11.

Polhemus D, Calvert J, Butler J, Lefer D . The cardioprotective actions of hydrogen sulfide in acute myocardial infarction and heart failure. Scientifica (Cairo). 2014; 2014:768607. PMC: 4090472. DOI: 10.1155/2014/768607. View

12.

Stacko P, Muchova L, Vitek L, Klan P . Visible to NIR Light Photoactivation of Hydrogen Sulfide for Biological Targeting. Org Lett. 2018; 20(16):4907-4911. DOI: 10.1021/acs.orglett.8b02043. View

13.

Zhao Y, Pluth M . Hydrogen Sulfide Donors Activated by Reactive Oxygen Species. Angew Chem Int Ed Engl. 2016; 55(47):14638-14642. PMC: 5175466. DOI: 10.1002/anie.201608052. View

14.

Zheng Y, Ji X, Ji K, Wang B . Hydrogen sulfide prodrugs-a review. Acta Pharm Sin B. 2015; 5(5):367-77. PMC: 4629439. DOI: 10.1016/j.apsb.2015.06.004. View

15.

Powell C, Foster J, Okyere B, Theus M, Matson J . Therapeutic Delivery of HS via COS: Small Molecule and Polymeric Donors with Benign Byproducts. J Am Chem Soc. 2016; 138(41):13477-13480. PMC: 5074078. DOI: 10.1021/jacs.6b07204. View

16.

Zhao Y, Henthorn H, Pluth M . Kinetic Insights into Hydrogen Sulfide Delivery from Caged-Carbonyl Sulfide Isomeric Donor Platforms. J Am Chem Soc. 2017; 139(45):16365-16376. PMC: 6022369. DOI: 10.1021/jacs.7b09527. View

17.

Zhao Y, Steiger A, Pluth M . Cysteine-activated hydrogen sulfide (HS) delivery through caged carbonyl sulfide (COS) donor motifs. Chem Commun (Camb). 2018; 54(39):4951-4954. PMC: 5965689. DOI: 10.1039/c8cc02428f. View

18.

Lin V, Chang C . Fluorescent probes for sensing and imaging biological hydrogen sulfide. Curr Opin Chem Biol. 2012; 16(5-6):595-601. PMC: 3509267. DOI: 10.1016/j.cbpa.2012.07.014. View

19.

Balazy M, Abu-Yousef I, Harpp D, Park J . Identification of carbonyl sulfide and sulfur dioxide in porcine coronary artery by gas chromatography/mass spectrometry, possible relevance to EDHF. Biochem Biophys Res Commun. 2003; 311(3):728-34. DOI: 10.1016/j.bbrc.2003.10.055. View

20.

Powell C, Dillon K, Matson J . A review of hydrogen sulfide (HS) donors: Chemistry and potential therapeutic applications. Biochem Pharmacol. 2017; 149:110-123. PMC: 5866188. DOI: 10.1016/j.bcp.2017.11.014. View