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

  • Front Pharmacol. 2022 Jul 6:13:842316. doi: 10.3389/fphar.2022.842316.
Kirill Kirsanov  1  2 ,  Timur Fetisov  1 ,  Elena Antoshina  1 ,  Lubov Trukhanova  1 ,  Tatiana Gor'kova  1 ,  Olga Vlasova  1 ,  Irina Khitrovo  1 ,  Ekaterina Lesovaya  1  3 ,  Nataliya Kulbachevskaya  1 ,  Tatiana Shcherbakova  4 ,  Gennady Belitsky  1 ,  Marianna Yakubovskaya  1 ,  Vytas Švedas  4  5 ,  Dmitry Nilov  4
Affiliations
  • 1. Blokhin Cancer Research Center, Moscow, Russia.
  • 2. Peoples' Friendship University of Russia, Moscow, Russia.
  • 3. Pavlov Ryazan State Medical University, Ryazan, Russia.
  • 4. Belozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, Russia.
  • 5. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia.
PMID: 35873588 DOI: 10.3389/fphar.2022.842316
Abstract

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.

Keywords
7-Methylguanine; cancer; carcinogenicity; inhibitor; toxicity.
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