Frontiers in Pharmacology (Jul 2022)

Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity

  • Kirill Kirsanov,
  • Kirill Kirsanov,
  • Timur Fetisov,
  • Elena Antoshina,
  • Lubov Trukhanova,
  • Tatiana Gor’kova,
  • Olga Vlasova,
  • Irina Khitrovo,
  • Ekaterina Lesovaya,
  • Ekaterina Lesovaya,
  • Nataliya Kulbachevskaya,
  • Tatiana Shcherbakova,
  • Gennady Belitsky,
  • Marianna Yakubovskaya,
  • Vytas Švedas,
  • Vytas Švedas,
  • Dmitry Nilov

DOI
https://doi.org/10.3389/fphar.2022.842316
Journal volume & issue
Vol. 13

Abstract

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7-Methylguanine (7-MG) competitively inhibits the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) and RNA-modifying enzyme tRNA-guanine transglycosylase (TGT) and represents a potential anticancer drug candidate. Furthermore, as a natural compound, it could escape the serious side effects characteristic for approved synthetic PARP inhibitors. Here we present a comprehensive study of toxicological and carcinogenic properties of 7-MG. It was demonstrated that 7-MG does not induce mutations or structural chromosomal abnormalities, and has no blastomogenic activity. A treatment regimen with 7-MG has been established in mice (50 mg/kg per os, 3 times per week), exerting no adverse effects or changes in morphology. Preliminary data on the 7-MG anticancer activity obtained on transplantable tumor models support our conclusions that 7-MG can become a promising new component of chemotherapy.

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