Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide

Waters, James K.; Kelley, Steven P.; Mossine, Valeri V.; Mawhinney, Thomas P.

doi:10.3390/ph13100270

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Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide

¹

Experiment Station Chemical Laboratories, University of Missouri, Columbia, MO 65211, USA

²

Department of Chemistry, University of Missouri, Columbia, MO 65211, USA

³

Department of Biochemistry, University of Missouri, Columbia, MO 65211, USA

^*

Author to whom correspondence should be addressed.

Pharmaceuticals 2020, 13(10), 270; https://doi.org/10.3390/ph13100270

Submission received: 6 September 2020 / Revised: 19 September 2020 / Accepted: 23 September 2020 / Published: 25 September 2020

(This article belongs to the Section Medicinal Chemistry)

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Abstract

S-Carboxymethyl-L-cysteine (CMC) is an antioxidant and mucolytic commonly prescribed to patients with chronic obstructive pulmonary disease. In humans, CMC is rapidly metabolized to S-carboxymethyl-L-cysteine sulfoxide (CMCO). In this study, we assessed structural and functional similarities between CMC and CMCO. X-Ray diffraction analysis provided detailed structural information about CMCO, which exists as a 1:1 mixture of epimers, due to the emergence of a new chiral center at the sulfur atom. Both CMC and CMCO epimers protected model DNA from copper-mediated hydroxyl free radical damage. Using an insulated transposable construct for reporting activity of the cellular stress-responsive transcription factors Nrf2, p53, NF-κB, and AP-1, we demonstrate that CMCO, especially its (4R)-epimer, is comparable to CMC in their ability to mitigate the effects of oxidative stress and pro-inflammatory stimuli in human alveolar (A549) and bronchial epithelial (BEAS-2B) cells. The results of these in vitro studies suggest that CMCO retains, at least partially, the antioxidant potential of CMC and may inform pharmacodynamics considerations of CMC use in clinics.

Keywords: COPD; carbocisteine; crystal structure; tumor necrosis factor; hydrogen peroxide; hydroquinone; cigarette smoke extract

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MDPI and ACS Style

Waters, J.K.; Kelley, S.P.; Mossine, V.V.; Mawhinney, T.P. Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide. Pharmaceuticals 2020, 13, 270. https://doi.org/10.3390/ph13100270

AMA Style

Waters JK, Kelley SP, Mossine VV, Mawhinney TP. Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide. Pharmaceuticals. 2020; 13(10):270. https://doi.org/10.3390/ph13100270

Chicago/Turabian Style

Waters, James K., Steven P. Kelley, Valeri V. Mossine, and Thomas P. Mawhinney. 2020. "Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide" Pharmaceuticals 13, no. 10: 270. https://doi.org/10.3390/ph13100270

APA Style

Waters, J. K., Kelley, S. P., Mossine, V. V., & Mawhinney, T. P. (2020). Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide. Pharmaceuticals, 13(10), 270. https://doi.org/10.3390/ph13100270

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Structure, Antioxidant and Anti-inflammatory Activities of the (4R)- and (4S)-epimers of S-Carboxymethyl-L-cysteine Sulfoxide

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