Mannich Base Derivatives as the Potential Candidates of Human Topoisomerase II Inhibitors
Mannich bases are pharmacologically important molecules having wide range of bioactivities. We previously
synthesized and characterized a number of Mannich base derivatives of planar polycyclic/heterocyclic starting materials
of which four of them [MB1 (3-(bis(2-chloroethyl)amino)-1-phenylpropan-1-one hydrochloride), MB2 (3-(bis(2-
chloroethyl)amino)-1-(naphthalen-2-yl)propan-1-one hydrochloride), MB3 (3-(bis(2-chloroethyl)amino)-1-(phenanthren-
3-yl)propan-1-one hydrochloride) and MB4(3-morpholino-1-(pyren-1-yl)propan-1-one hydrochloride)] manifested antiproliferative
effects in three cancer cell lines (PC3, HeLa, and MCF7) and one non-tumoral cell line (293 HEK). Because
several reports covering anti-proliferation address DNA topoisomerases as the cellular targets, we undertook further assays
using these four compounds with type I and type II topoisomerases to identify if their effects were mediated through
topoisomerase reactions. Our results indicated that the three of these compounds (MB2, MB3 and MB4) target topoisomerase
II without affecting type I topoisomerase. However, targeting type II enzyme did not generate considerable
strand breaks, which in turn places the compounds MB2, MB3 and MB4 in potential topoisomerase II inhibitors, not poisons.
Keywords: Anti-tumor drugs, DNA topoisomerases, mannich bases.
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