Background: Inhibition of the DNA repair enzyme, tyrosyl-DNA phosphodiesterase 1 (TDP1), may increase the efficacy of cancer drugs that cause damage to tumor cell DNA. Among the known TDP1 inhibitors, there are compounds containing moieties of natural substances, e.g., monoterpenoids. In this work, we synthesized several compounds containing aromatic/ heteroaromatic amines and monoterpenoid groups and assessed their TDP1 inhibition potential. Methods: Structures of all the synthesized compounds were confirmed by 1H and 13C NMR as well as HRMS. The TDP1 inhibitory activity of the amines was determined by real-time fluorescence oligonucleotide biosensor. Results: The synthesized secondary amines had TDP1 inhibitory activity IC50 in the range of 0.79-9.2 µM. The highest activity was found for (–)-myrtenal derivatives containing p-bromoaniline or m-(trifluoromethyl)aniline residue. Conclusion: We synthesized 22 secondary amines; of these, 17 amines are novel chemical structures. Many of the amines inhibit TDP1 activity in the low micromolar range. Therefore, these compounds are promising for further study of their antiproliferative activity in conjunction with DNA damaging drugs.

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irogova 2, RU-630090 Novosibirsk c )Boreskov Institute of Catalysis,p r. Lavrentieva, 5, RU-630090 Novosibirsk Ap utative acid metabolite of an ovel highly effective antiparkinsonian agent, (4S,5R,6R)-5,6dihydroxy-4-(prop-1-en-2-yl)cyclohex-1-ene-1-carboxylic acid (5), was synthesizedf or the first time. Several synthetic approaches based on different transformations of O-bearing monoterpenoids of the pinane and p-menthanes eries were developed and tested in the course of the study.A cid 5 was synthesized starting from ac ommercially available monoterpenoid, (À)-verbenone,i natotal yield of 4.4% over eightsteps. Helv eticaChimica Acta -V ol. 98 (2015)1 443 Scheme 1. Syntheses of Triol 3 and Aldehyde 6 Helv eticaChimica Acta -V ol. 98 (2015) 1444 Scheme 2. Transformations of 6 and Structureof11 Scheme3. Synthesisa nd Rearrangements of (À)-cis-Verbenol Epoxide (12) Helv eticaChimica Acta -V ol. 98 (2015)1 445 Scheme 4. Synthesis of 19 Helv eticaChimica Acta -V ol. 98 (2015)1 447 Scheme 6. Possible Mechanism of the Formation of 24 Scheme 7. Transformationso f 22