Therapeutics
The importance of heterocyclic compounds in anti-cancer drug design
Heterocycles are key structural components of many of the anti-cancer drugs available on the market today. Indeed, of the novel molecular anti-cancer agents approved by the FDA between 2010 and 2015, almost two-thirds contained heterocyclic rings within their structures. Their prevalence in anti-cancer drug design can be partly attributed to their being extremely common in nature, with a vast number of cellular processes and mechanisms having evolved the ability to interact with them. Their versatility means there are multiple metabolic pathways and cellular processes within cancer pathology that can be susceptible to heterocycle-based drugs. In this article, we look at some of the most important heterocyclic compounds currently implicated in cancer therapy, both on the market and in development, discuss the properties that make them valuable as anti-cancer drugs, and consider the benefits of including heterocycles within high-throughput screening libraries.
By Simon Pearce
D
efined as cyclic compounds containing ring member atoms of carbon and at least one other element (such as nitro- gen, oxygen and sulfur), heterocycles are com- mon in biology, featuring in a wide range of structures from enzyme co-factors through to amino acids and proteins. They play a vital role in the metabolism of all living things, and are utilised at almost every stage of the many bio- chemical processes necessary to sustain life. Their prevalence is partly down to the broad range of interactions these structures are involved with, made possible due to the physico- chemical properties of their heteroatoms that can behave as either acids or bases, depending on the pH of their environment1.
The ability of heterocycles to engage in a wide 66
variety of intermolecular interactions, including hydrogen bond donor/acceptor capability, pi- stacking interactions, metal co-ordination bonds as well as van der Waals and hydrophobic forces, allows them to bind with enzymes in a multitude of ways. In addition, their wide range of ring sizes and structural permutations means heterocycles come in a broad range of shapes and sizes, allow- ing them to match the equally diverse structural range of enzyme binding pockets. With their functional versatility, extremely com- mon occurrence in nature, and involvement in large numbers of biological pathways, will the increased investment in heterocyclic-based anti- cancer drug design continue to justify their place in the race to combatting one of the world’s most dev- astating diseases?
Drug Discovery World Summer 2017
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72
