Collaborative virtual screening to elaborate an imidazo[1,2- <i>a</i> ]pyridine hit series for visceral leishmaniasis
Yuichiro Akao, Stacie Canan, Yafeng Cao, Kevin R. Condroski, Ola Engkvist, Sachiko Itono, Rina Kaki, C. Kimura, Thierry Kogej, Kazuya Nagaoka, Akira Naito, Hiromi Nakai, Garry Pairaudeau, Constantin Radu, Ieuan O. Roberts, Mitsuyuki Shimada, David Shum, Naoaki Watanabe, Huanxu Xie, Shuji Yonezawa, Osamu Yoshida, Ryu Yoshida, Charles E. Mowbray, Benjamin Perry
Abstract
probing of five proprietary pharmaceutical company libraries enabled rapid expansion of the hit chemotype, alleviating initial concerns about the core chemical structure while simultaneously improving antiparasitic activity and selectivity index relative to the background cell line. Subsequent hit optimization informed by the structure-activity relationship enabled by this virtual screening allowed thorough investigation of the pharmacophore, opening avenues for further improvement and optimization of the chemical series.