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

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 chara...

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Main Authors: Kirill Kirsanov, Timur Fetisov, Elena Antoshina, Lubov Trukhanova, Tatiana Gor’kova, Olga Vlasova, Irina Khitrovo, Ekaterina Lesovaya, Nataliya Kulbachevskaya, Tatiana Shcherbakova, Gennady Belitsky, Marianna Yakubovskaya, Vytas Švedas, Dmitry Nilov
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-07-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2022.842316/full
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Summary: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.
ISSN:1663-9812