Multi-Target Directed Indole Based Hybrid Molecules in Cancer Therapy : An Up-To-Date Evidence-Based Review.

Abstract

Cancer is a multifactorial disease and most of its types still remain incurable, in spite of enormous efforts to explicate various tumor pathophysiology. The anti-cancer drug discovery paradigm "one-compound-one-target" has failed and subsequently shifted to two-drug cocktail and recently the "multi-target approach" in order to design and develop agents able to act simultaneously on multiple intracellular constituents and signaling pathways. Novel hybrid compounds are now designed by incorporating two covalently linked independently acting pharmacores, each efficient at combating cancer. They can deliver synergistic effects from the dual action of both independently acting moieties by interacting with multiple targets. These composite molecules are also less prone to drug resistance, leading to an improved pharmacological potency than each individual moiety. As indole nucleus is a central component of many natural and synthetic molecules with extensive biological activity, this review incorporates a variety of such hybrid compounds with indole moiety as one of the active units, where better therapeutic effect has been successfully achieved, by either simultaneous or sequential action of individual functional pharmacore. The current limitations and challenges encountered in the development of these hybrid agents are also discussed.