Deuterium labeling improves the therapeutic index of 3,3'-diselenodipropionic acid as an anticancer agent: insights from redox reactions.

Autor: Gandhi VV; Radiation and Photochemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India kamit@barc.gov.in 91 22 25505151 91 22 25592352/25595399.; Homi Bhabha National Institute Anushaktinagar Mumbai - 400 094 India., Pal MK; Chemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India dsandip@barc.gov.in 91 22 25592589., Singh BG; Radiation and Photochemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India kamit@barc.gov.in 91 22 25505151 91 22 25592352/25595399.; Homi Bhabha National Institute Anushaktinagar Mumbai - 400 094 India., Das RP; Radiation and Photochemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India kamit@barc.gov.in 91 22 25505151 91 22 25592352/25595399., Wadawale AP; Chemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India dsandip@barc.gov.in 91 22 25592589., Dey S; Chemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India dsandip@barc.gov.in 91 22 25592589.; Homi Bhabha National Institute Anushaktinagar Mumbai - 400 094 India., Kunwar A; Radiation and Photochemistry Division, Bhabha Atomic Research Centre Mumbai - 400085 India kamit@barc.gov.in 91 22 25505151 91 22 25592352/25595399.; Homi Bhabha National Institute Anushaktinagar Mumbai - 400 094 India.
Jazyk: angličtina
Zdroj: RSC medicinal chemistry [RSC Med Chem] 2024 May 06; Vol. 15 (6), pp. 2165-2178. Date of Electronic Publication: 2024 May 06 (Print Publication: 2024).
DOI: 10.1039/d4md00105b
Abstrakt: 3,3'-Diselenodipropionic acid (DSePA), a selenocystine derivative, has been previously reported as an oral supplement for anticancer/radio-modulation activities. The present study is focused on devising a strategy to synthesize and characterize the deuterated derivative of DSePA and on understanding the effect of deuteration on its therapeutic index by comparing its cytotoxicity in cancerous versus non-cancerous cell types. In this context, the synthesis of 3,3'-diselenodipropionic acid-D 8 (D-DSePA) was accomplished in ∼42% yield. Further, the results clearly established that the deuteration of DSePA significantly reduced its cytotoxicity in non-cancerous cell types while retaining its cytotoxicity in cancerous cell lines. Together, D-DSePA displayed a ∼5-fold higher therapeutic index than the non-deuterated derivative for anticancer activity. The biochemical and NMR studies confirmed that the better biocompatibility of D-DSePA than its non-deuterated derivative in non-cancerous cells was due to its ability to undergo slower redox reactions and to cause lesser inhibition of intracellular redox enzymes.
Competing Interests: None.
(This journal is © The Royal Society of Chemistry.)
Databáze: MEDLINE
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