Structure-Function Study of Symmetrically Substituted Pyridine Derivatives Based on the Iron binding Site of Bleomycin

Abstract

Symmetrical molecules were designed based on the bleomycin iron-binding site leading to an unexpected finding of a zinc-binding molecule SN-1. SN-1 and its derivatives inhibited/regulated zinc finger proteins HIV-EP1, farnesyltransferase, APOBEC3G, TRAF6, and ADAM17. HPH-15 was identified by a phenotype screening of a library of SN-1 derivatives, judging based on the cell morphological changes during epithelial mesenchymal transition of fibroblast. Structural characteristics of HPH-15 are side chains containing a thioamide and a S-tert-butyl group. HPH-15 was found to be effective against diabetes, fatty liver, and skin/liver fibrosis.