Combinatorial Approaches in Anticancer Drug Discovery: Recent Advances in Design and Synthesis

Abstract

Combinatorial technology for the generation of molecular diversity has evolved as an integrated component in accelerated drug discovery process. During the emerging days of combinatorial chemistry, solid-phase organic synthesis has been the leading strategy for the production of large libraries for lead discovery. As combinatorial techniques for the library synthesis has evolved, solution-phase synthesis of smaller, targeted libraries is gaining attention. Numerous syntheses of biologically active chemical libraries of small molecules have been reported during the past decade. This review will focus only on the recent literature of chemical libraries targeted towards anticancer properties. The synthesis, chemistry and biological activity of these libraries as anticancer agents are summarized.

Recent Innovations in Peptide Based Targeted Drug Delivery to Cancer Cells

“…At the end of the synthesis the peptides are directly subjected to a biological screening or are first removed from the pins by enzymatic [12] or chemical [13] cleavage. Several different combinatorial methods and techniques have since been introduced [14,15,16], and the field of synthetic peptide libraries has now become a powerful tool for drug discovery [17,18,19] as well as for fundamental biological investigation [20,21]. In the context of synthetic homing peptides, the one-bead-one-compound (OBOC) method has made a particular impact [22].…”

Combinatorial chemistry in cancer research

“…Bhattacharyya [63] published an extensive review of combinatorial approaches for the design and synthesis of new anticancer drugs. Noteworthy libraries mentioned in the review include two libraries consisting of 476.775 and of 114.783.975 polyamides, respectively, based on iminodiacetic acid and tested as modulators of protein-protein interactions of interest in cancer treatment (Fig.…”

Exploring Novel Target Space: A Need to Partner High Throughput Docking and Ligand-Based Similarity Searches?

“…Genome-based discoveries of this magnitude provide exciting and challenging opportunities for drug discovery scientists, however this novel target space must be validated in terms of therapeutic drugability, disease causality and overall importance in the pathological presentation of disease. These discovery based initiatives build upon other recent success in the areas of combinatorial chemistry (CC) and High throughput screening (HTS) [4,5], success that has permitted scientists to explore and thus understand the mechanistic details of these target-ligand interactions at the molecular and cellular level ( [6][7][8] and references therein). However, these powerful approaches have resulted in a limited number of new chemical entities (NCEs) or clinically approved compounds, which is a significant disappointment that is further compounded when one considers the reproducibility and cost issues associated with these approaches (estimated at $500,000-$1,000,000).…”