Background: Topoisomerases are a set of nuclear enzymes that play a vital
role in handling of topological consequences of DNA during various genetic activities
necessary for vitality of cell. Inhibition of these enzymes consequently leads to the
blockage of ligation step of the cell cycle which generates single and double strand
breakage in DNA strand. Introduction of these breaks subsequently leads to programmed
cell death (Apoptosis).
Objective: In the past several years, topoisomerases have become one of the most
expedient and strategic molecular targets for anticancer drugs and numerous patents
have been filed and published on topoisomerase inhibitors. This review compiles the
patent literature up to 2016 embracing topo I and II inhibitors as well as dual inhibitors
which are structurally adjacent to camptothecin (CPT), natural products such as lamellarins and synthetic
trisubstituted pyridines. The present assemblage can be extremely advantageous for the medicinal
chemists who are in crave for the development of potential anticancer agents targeting topoisomerases.
Conclusion: Recent patents indicated that some of the nitrogen containing heteroaromatic compounds
have immense potential to inhibit topoisomerase enzyme. In particular, fused N-Heterocycles can be anticipated
for their promising therapeutic potential alone or in combination with other anticancer agents.
Naphthyridinone and indenoisoquinoline derivatives, described in the preceding sections of this review,
are endowed with significant potency against topoisomerase I which clearly indicates the need of preclinical
and clinical studies to place them in forefront as potential future drug candidates.