Author/Authors :
Nilov, D.K. Lomonosov Moscow State University, russia , Tararov, V.I. Engelhardt Institute of Molecular Biology - Russian Academy of Sciences, russia , Kulikov, A.V. Lomonosov Moscow State University, russia , Zakharenko, A.L. Institute of Chemical Biology and Fundamental Medicine - Russian Academy of Sciences - Siberian Branch, russia , Gushchina, I.V. Lomonosov Moscow State University, russia , Mikhailov, S.N. Engelhardt Institute of Molecular Biology - Russian Academy of Sciences, russia , Lavrik, O.I. Institute of Chemical Biology and Fundamental Medicine - Russian Academy of Sciences - Siberian Branch, russia , Švedas, V.K. Lomonosov Moscow State University, russia
Abstract :
108 | ACTA NATURAE | VOL. 8 No 2 (29) 2016RESEARCH ARTICLESABSTRACT The ability of 7-methylguanine, a nucleic acid metabolite, to inhibit poly(ADP-ribose)polymerase-1 (PARP-1) and poly(ADP-ribose)polymerase-2 (PARP-2) has been identified in silico and studied experimentally. The amino group at position 2 and the methyl group at position 7 were shown to be important substituents for the efficient binding of purine derivatives to PARPs. The activity of both tested enzymes, PARP-1 and PARP-2, was suppressed by 7-methylguanine with IC50 values of 150 and 50 μM, respectively. At the PARP inhibitory con-centration, 7-methylguanine itself was not cytotoxic, but it was able to accelerate apoptotic death of BRCA1-de-ficient breast cancer cells induced by cisplatin and doxorubicin, the widely used DNA-damaging chemothera-peutic agents. 7-Methylguanine possesses attractive predictable pharmacokinetics and an adverse-effect profile and may be considered as a new additive to chemotherapeutic treatment.
