The key objective of this research is to synthesize a range of novel indole-based heterocyclic molecules that can potentially be used for multi-targeted cancer therapies in combination with clinical doses of HDAC inhibitors.The work therefore consists of the design and synthesis of novel indole scaffolds as well as their systematic pre-clinical in vitro evaluation against human cancer cell lines in combination with HDAC inhibitors.A variety of unique indole-based fused systems has been developed by using different synthetic methodology.Key monomeric and dimericpyranoindole systems have been prepared through treatment of a dihydroxyindoles with β-keto esters while related monomeric and dimericfuranoindole scaffolds has been prepared through treatment of dihydroxyindoles with α-halo ketones.