Isoflavonoids and Epigenetic Modulation: Therapeutic Insights for Cancer Treatment

TL;DR

This paper explores how isoflavonoids, especially pterocarpans, can modulate epigenetic processes and offer new cancer treatment possibilities, particularly in leukemia.

Contribution

The paper highlights the epigenetic potential of (+)-2,3,9-trimethoxypterocarpan as a promising candidate for leukemia treatment.

Findings

(+)‐2,3,9‐trimethoxypterocarpan shows high gastrointestinal absorption and can cross the blood–brain barrier in silico.

P-glycoprotein is a substrate for the molecule, indicating active efflux potential from the blood–brain barrier and gastrointestinal tract.

In silico models like SwissADME support the molecule's favorable pharmacokinetic properties.

Abstract

Isolavonoides represent the second largest subgroup of flavonoids and have an influence on critical molecular pathways and restore cellular homeostasis, through the reprogramming of epigenetic regulatory mechanisms. This feature indicates a crucial therapeutic potential that could be better explored to attend cancer treatment. Isoflavonoids, acting as epigenetic modulators, could contribute to the development of new therapeutic approaches in cancer, especially in onco‐hematological diseases. Pterocarpans are a subgroup of isoflavonoids that have been extensively studied for their biological properties. The molecule (+)‐2,3,9‐trimethoxypterocarpan demonstrates high gastrointestinal (GI) absorption and the ability to cross the blood–brain barrier (BBB) in silico without violating Lipinski's rule, making it a desirable candidate in leukemia treatment. The synthesis of this molecule dates back more than a decade. In silico models, such as SwissADME, corroborate the notion of good intestinal absorption and the ability to cross the BBB. Also, it is suggested that P‐glycoprotein is a substrate, which is related to its potential for active efflux from both the BBB and GI. This review highlights the biological mechanisms of this class of natural products from a translational perspective, emphasizing their chemical properties and epigenetic biological activities, which offer new therapeutic perspectives, particularly in oncology.

Venn diagram illustrating the epigenetic roles of three phytochemical groups—flavonoids, isoflavonoids, and pterocarpans.

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