Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8329714 | International Journal of Biological Macromolecules | 2016 | 32 Pages |
Abstract
Two new spiro-acridines were synthesized by introducing cyano-N-acylhydrazone between the acridine and phenyl rings followed by spontaneous cyclization. The final compounds (E)-1⿲-(benzylideneamino)-5⿲-oxo-1⿲,5⿲-dihydro-10H-spiro[acridine-9,2⿲-pyrrole]-4⿲-carbonitrile (AMTAC-01) and (E)-1⿲-((4-methoxybenzylidene)amino)-5⿲-oxo-1⿲,5⿲-dihydro-10H-spiro[acridine-9,2⿲-pyrrole]-4⿲-carbonitrile (AMTAC-02) were evaluated for their interactions with calf thymus DNA, antiproliferative and human topoisomerase I and IIα inhibitory activities. Both compounds presented ability to bind DNA. The binding constant determined by UV⿿vis spectroscopy was found to be 104 M⿿1. Antiproliferative assay demonstrated that AMTAC-01 and AMTAC-02 were most active against prostate and melanoma tumor cell lines, respectively. The compound did not present Topo I inhibitory activity. However, both derivatives displayed topoisomerase IIα inhibitory activity comparable to amsacrine, and AMTAC-02 was more potent than AMTAC-01 with methoxy substituent group on phenyl ring. This study demonstrates that the new derivatives are promising molecules with topoisomerase IIα inhibitory and antiproliferative activities.
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Authors
Sinara Mônica Vitalino de Almeida, Elizabeth Almeida Lafayette, Willams Leal Silva, Vanessa de Lima Serafim, Thais Meira Menezes, Jorge Luiz Neves, Ana Lucia Tasca Gois Ruiz, João Ernesto de Carvalho, Ricardo OlÃmpio de Moura,