Synthesis, biological evaluation and molecular modeling of imidazo[1,2-a]pyridine derivatives as potent antitubulin agents

Add time:08/11/2019    Source:sciencedirect.com

Two series of novel 5,7-diarylimidazo[1,2-a]pyridine-8-carbonitrile derivatives (3a–3q and 7a–7n) were designed by modification of CA-4 pharmacophore to develop colchicine targeted antitubulin agents. All compounds were efficiently synthesized and evaluated for their cytotoxicity against five selected cancer cell lines (HT-29, H460, A549, MKN-45 and SMMC-7721) which got an insight in structure and activity relationships (SARs). Several molecules (7e, 7f, 7h–7j and 7m) were disclosed to exhibit promising antiproliferative activity with IC50 values in double-digit nanomolar degree. Optimization toward these compounds led to the discovery of a promising lead 7e, which showed noteworthy potency with IC50 value ranging from 0.01 to 3.2 µM superior to CA-4 and Crolibulin. Importantly, immunofluorescence staining and colchcine competitive binding assay revealed that microtubule dynamics was disrupted by 7e by binding at the colchicine site of tubulin. Moreover, molecular docking studies suggested the binding of this mimic at colchcine-binding site is similar to Crolibulin, as was in conformity with the observed SARs for these compounds.

We also recommend Trading Suppliers and Manufacturers of 2-Cyano-4-(pyrrolidin-1-yl)pyridine (cas 127680-86-8). Pls Click Website Link as below: cas 127680-86-8 suppliers

Prev:Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): A highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Next:β-3-furylalanine, a new analog of phenylalanine)