Pyridine based antitumor compounds acting at the colchicine site

July 1, 2016, Bentham Science Publishers

Tubulin inhibitors are amongst the most successful anti-cancer, anti-parasitic and herbicidal agents. Their vascular disrupting activity has recently attracted research focus as it elicits anti-cancer effects at doses well below that of other toxic agents. The colchicine site of tubulin is located in a hydrophobic region at the interface of the tubulin α,β-dimer.

Ligands binding at the colchicine site occupy different pockets and make different types of interactions with the protein. Colchicine site agents are structurally simple, and synthetically accessible anti-tubulin agents are in active development. But these agents suffer from poor pharmacokinetics. The incorporation of pyridines and related nitrogenated heterocycles in the structures of colchicine site agents has resulted in new active scaffolds, improved potencies and pharmacokinetic improvements for binding with colchicine site ligands.

This article critically reviews the impact of such modifications in the field and in the future perspectives of this class of clinically successful agents. The colchicine binding drugs have been classified according to their described or presumed binding modes and the impact of the pyridine and related moieties on the activity for each compound class is discussed based on structure - property and structure - activity relationships, and on X-ray structures when available. Special emphasis has been made on drugs advancing to clinical trials and on proof of concept modifications.

From this analysis, a new insight into tubulin targeting is highlighted along with future perspectives for the development of similar site-specific .

Explore further: Success in the development of a gamma-tubulin specific inhibitor

More information: R. Álvarez et al, Pyridine Based Antitumour Compounds Acting at the Colchicine Site, Current Medicinal Chemistry (2016). DOI: 10.2174/092986732311160420104823

Related Stories

Parsley and dill help fight cancer, research shows

June 29, 2016

A collaborative of Russian scientists has proposed an efficient approach to novel agents with anticancer activity. A synthesis of these compounds is based on extracts from parsley and dill seeds. The results of the study ...

ESC: Colchicine effective for acute pericarditis

September 4, 2013

(HealthDay)—Colchicine is more effective than placebo in reducing the risk of incessant or recurrent pericarditis in patients with acute pericarditis, according to a study published online Sept. 1 in the New England Journal ...

FDA acts against unapproved colchicine

February 6, 2008

The U.S. Food and Drug Administration said it will take action against companies marketing unapproved injectable colchicine, a drug used to treat gout.

Recommended for you

Galactic center visualization delivers star power

March 21, 2019

Want to take a trip to the center of the Milky Way? Check out a new immersive, ultra-high-definition visualization. This 360-movie offers an unparalleled opportunity to look around the center of the galaxy, from the vantage ...

Ultra-sharp images make old stars look absolutely marvelous

March 21, 2019

Using high-resolution adaptive optics imaging from the Gemini Observatory, astronomers have uncovered one of the oldest star clusters in the Milky Way Galaxy. The remarkably sharp image looks back into the early history of ...

When more women make decisions, the environment wins

March 21, 2019

When more women are involved in group decisions about land management, the group conserves more—particularly when offered financial incentives to do so, according to a new University of Colorado Boulder study published ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.