Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II

Abstract

Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.

QSAR studies of imidazopyridine derivatives as Et-PKG inhibitors using the PSO-SVM approach

“…Et-PKG is essential for survival and represents a desirable therapeutic target (Scribner et al, 2007). Highthroughput screening of known kinase inhibitors resulted in the discovery of imidazopyridine derivatives as PKG inhibitors and broad-spectrum anticoccidial agents (Scribner et al, 2008). The imidazopyridine analogs were tested for in vitro efficacy via the Ten_K (Tenella kinase) assay, which measures inhibition of Et-PKG enzyme activity.…”

“…The studied compounds are 107 imidazopyridine derivatives, which were taken from the literature (Liang et al, 2007;Scribner et al, 2007Scribner et al, , 2008Biftu et al, 2006); their structures are shown in Table 1. These compounds were tested for in vitro efficacy using the Ten_K (Tenella kinase) assay.…”

“…Thus, the need to identify and develop new drugs for the control of coccidiosis is critically important. Recently, some groups (Scribner et al, 2008) reported on some novel anticoccidial agents with potent in vitro and in vivo activity against Eimeria parasites. It was determined that inhibition of parasite growth by these compounds was due to inhibition of the parasite-specific cyclic GMP (cGMP)-dependent protein kinase (PKG).…”

Predicting the activity of drugs for a group of imidazopyridine anticoccidial compounds

“…The experimental values for the IC 50 of the imidazopyridine anticoccidial compounds are taken from the literature [15] and presented in Table 1. The data set is randomly separated into a training set of 26 compounds and a test set of 12 compounds.…”

Synthesis, molecular docking and anti-mycobacterial evaluation of new imidazo[1,2-a]pyridine-2-carboxamide derivatives

“…Different compounds containing the moiety imidazo[1,2-a]pyridine have significant biological applications such as anti-mycobacterial [15e21], anticancer [22,23], antiviral [24e27], antimicrobial [28e30], anti-HIV [31], antiulcer [32,33], antihelminthic [34] and anticoccidial activity [35,36]. As a result of our interest in the synthesis of imidazopyridine-containing compounds and their antimicrobial activity [37], we initiated a program directed towards the synthesis of the new imidazopyridine amide derivatives.…”