Summary:
Topoisomerases are enzymes responsible for the unwinding of, positively or
negatively, supercoiled DNA, derived from the opening of the two strands, and
without them a cell cannot access its genetic information which leads to death
or
apoptosis. Topoisomerases seem to be a very promising target for the treatment
of
tumors and by the last decades a lot of work has been done to this path
resulting in the
development of numerous active compounds, synthetic or natural ones,
inhibitors/poisons of either Topoisomerase I and/or II. Many compounds, based
on a
polycyclic planar framework, intercalate DNA and inhibit these enzymes, so they
can
be used as chemotherapeutic agents in some forms of cancer. Among them, DACA, a
dual inhibitor of Topoisomerase I and II, has reached Phase II clinical trials.
Prompted
by the above, here, we describe the design and synthesis of some novel DACA
analogues in order to evaluate the effect of this structural modification on
the tumor
cell growth inhibition and the inhibition of Topoisomerases I and II. They
consist of a
planar acridine/acridinone chromophore fused with a thiazolo ring and possess a
carboxamide chain in C-2, crucial for the development of its activity
Keywords:
Acridine, Thiazol, Topoisomerase, Cancer, Carboxamide
