A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12-17 and urea heterodimers 18-22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea (14-17) and urea moieties (21 and 22). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.

• Klíčová slova
• 7-MEOTA-tacrine heterodimers, HL-60, calf thymus DNA, human dermal fibroblasts, topoisomerases,
• MeSH
• akridiny chemická syntéza   chemie   farmakologie   MeSH
• buňky A549 MeSH
• fibroblasty účinky léků   MeSH
• HL-60 buňky MeSH
• lidé MeSH
• proliferace buněk účinky léků   MeSH
• protinádorové látky chemická syntéza   chemie   farmakologie   MeSH
• screeningové testy protinádorových léčiv MeSH
• takrin chemie   farmakologie   MeSH
• thiomočovina chemie   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 7-methoxy-1,2,3,4-tetrahydroacridin-9-amine MeSH Prohlížeč
• akridiny MeSH
• protinádorové látky MeSH
• takrin MeSH
• thiomočovina MeSH