Biopolym. Cell. 2012; 28(3):239-241.
Short Communications
Polysulfide compounds as inhibitors of the key base excision repair enzymes
- Novosibirsk Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences
8, Akademika Lavrentieva Ave., Novosibirsk, Russian Federation, 630090 - N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences
9, Akademika Lavrentieva Ave., Novosibirsk, Russian Federation, 630090
Abstract
Aim. To increase the capacity of antitumor therapy based on DNA damage it is important to minimize the repair
of DNA lesions that can be achieved by inhibiting the activity of key DNA repair enzymes. To this end several
benzopentathiepine and benzo[1,3]dithiol derivatives were synthesized and tested as inhibitors of the key base
excision repair (BER) enzymes, PARP1, DNA polymerase β, and APE1. Methods. The procedure of synthesis of
several new compounds was developed. The inhibitory capacity of the compounds was estimated by comparison
of the enzyme activities in specific testsin the presence of compounds versustheir absence. Results. Benzopentathiepine derivative bearing trifluoromethyl group at the 1-st position was shown to be a weak inhibitor of
PARP1. Cyclic substituents at the 1-st position attached through amide bond bring about moderate enhancement of pol β inhibition. Each studied substituent at the 1-st position considerably increases the inhibition of
APE1-catalyzed hydrolysis of AP sites as compared to parent compound. Conclusions. Several new inhibitors of
BER enzymes were revealed. The directions for further modification of compounds to improve their inhibitory
activity were found out.
Keywords: DNA polymerase &beta, poly(ADP-ribose)polymerase 1, apurinic/apyrimidinic endonuclease 1, polysulfide, pentathiepine, inhibitor
Full text: (PDF, in English)
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