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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.842316/full |
| _version_ | 1818118026131668992 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Kirill Kirsanov |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T04:47:45Z |
| format | Article |
| id | doaj.art-7294f36025d44385b80528fb3d54bae7 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-11T04:47:45Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-7294f36025d44385b80528fb3d54bae72022-12-22T01:20:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-07-011310.3389/fphar.2022.842316842316Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer ActivityKirill Kirsanov0Kirill Kirsanov1Timur Fetisov2Elena Antoshina3Lubov Trukhanova4Tatiana Gor’kova5Olga Vlasova6Irina Khitrovo7Ekaterina Lesovaya8Ekaterina Lesovaya9Nataliya Kulbachevskaya10Tatiana Shcherbakova11Gennady Belitsky12Marianna Yakubovskaya13Vytas Švedas14Vytas Švedas15Dmitry Nilov16Blokhin Cancer Research Center, Moscow, RussiaPeoples’ Friendship University of Russia, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaPavlov Ryazan State Medical University, Ryazan, RussiaBlokhin Cancer Research Center, Moscow, RussiaBelozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBlokhin Cancer Research Center, Moscow, RussiaBelozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, RussiaFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, RussiaBelozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, Russia7-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.https://www.frontiersin.org/articles/10.3389/fphar.2022.842316/full7-Methylguanineinhibitorcancercarcinogenicitytoxicity |
| spellingShingle | 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 Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity Frontiers in Pharmacology 7-Methylguanine inhibitor cancer carcinogenicity toxicity |
| title | Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity |
| title_full | Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity |
| title_fullStr | Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity |
| title_full_unstemmed | Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity |
| title_short | Toxicological Properties of 7-Methylguanine, and Preliminary Data on its Anticancer Activity |
| title_sort | toxicological properties of 7 methylguanine and preliminary data on its anticancer activity |
| topic | 7-Methylguanine inhibitor cancer carcinogenicity toxicity |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.842316/full |
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