Synthesis and initial screening of lactate dehydrogenase inhibitor activity of 1,3-benzodioxole derivatives.

Scientific Reports
Dicky AnnasKang Hyun Park

Abstract

Cancer is one of the main causes of mortality in the world. Many cancer cells produce ATP through high-level lactic acid fermentation catalyzed by lactate dehydrogenase (LDH), which converts pyruvic acid to lactic acid. LDH plays a dominant role in the Warburg effect, wherein aerobic glycolysis is favored over oxidative phosphorylation. Due to the high lactic acid production level in cancer cells, LDH-targeting could be a potential cancer treatment strategy. A few approaches, such as drug treatment, reportedly inhibited LDH activity. In this study, we describe new 1,3-benzodioxole derivatives that might be potential small molecule candidates for LDHA inhibition. The synthesis was carried out by trans-esterification between aryl ester and alcohol groups from piperonyl alcohol. Compounds 2 and 10 exhibited a selective LDHA IC50 value of 13.63 µM and 47.2 µM, respectively. Whereas only compound 10 showed significant cytotoxicity in several lines of cancer cells, especially in human pancreatic cancer PANC-1 cells. These synthesized compounds possess 2 aromatic rings and -CF3 moiety, which expectedly contributes to LDHA inhibition. The presented products have the potential to become a promising LDHA inhibitor drug candidate.

References

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Citations

Jan 21, 2021·International Journal of Molecular Sciences·Russel J ReiterSergio Rosales-Corral
Apr 4, 2021·Biomedicines·Alberto Cruz-BermúdezMariano Provencio

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Methods Mentioned

BETA
NMR
column chromatography

Software Mentioned

Xcalibur
PRISM

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