39075-92-8Relevant articles and documents
Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors
Mondal, Santanu,Gong, Xuefeng,Zhang, Xiaoqian,Salinger, Ari J.,Zheng, Li,Sen, Sudeshna,Weerapana, Eranthie,Zhang, Xuesen,Thompson, Paul R.
supporting information, p. 12476 - 12480 (2019/08/07)
Protein arginine deiminases (PADs) hydrolyze the side chain of arginine to form citrulline. Aberrant PAD activity is associated with rheumatoid arthritis, multiple sclerosis, lupus, and certain cancers. These pathologies established the PADs as therapeutic targets and multiple PAD inhibitors are known. Herein, we describe the first highly potent PAD1-selective inhibitors (1 and 19). Detailed structure–activity relationships indicate that their potency and selectivity is due to the formation of a halogen bond with PAD1. Importantly, these inhibitors inhibit histone H3 citrullination in HEK293TPAD1 cells and mouse zygotes with excellent potency. Based on this scaffold, we also developed a PAD1-selective activity-based probe that shows remarkable cellular efficacy and proteome selectivity. Based on their potency and selectivity we expect that 1 and 19 will be widely used chemical tools to understand PAD1 biology.
Design, synthesis, and biological activities of closantel analogues: Structural promiscuity and its impact on onchocerca volvulus
Garner, Amanda L.,Gloeckner, Christian,Tricoche, Nancy,Zakhari, Joseph S.,Samje, Moses,Cho-Ngwa, Fidelis,Lustigman, Sara,Janda, Kim D.
experimental part, p. 3963 - 3972 (2011/08/05)
Onchocerciasis, or river blindness, is a neglected tropical disease that affects more than 37 million people worldwide, primarily in Africa and Central and South America. We have disclosed evidence that the larval-stage-specific chitinase, OvCHT1, may be a potential biological target for affecting nematode development. On the basis of screening efforts, closantel, a known anthelmintic drug, was discovered as a potent and highly specific OvCHT1 inhibitor. Originally, closantel's anthelmintic mode of action was believed to rely solely on its role as a proton ionophore; thus, the impact of each of its biological activities on O. volvulus L3moltingwas investigated. Structure-activity relationship studies on an active closantel fragment are detailed, and remarkably, by use of a simple salicylanilide scaffold, compounds acting only as protonophores or chitinase inhibitors were identified. From these data, unexpected synergistic protonophore and chitinase inhibition activities have also been found to be critical for molting in O. volvulus L3 larvae.
Synthetic study of substituted arylsulfonylphenylbenzamides
Gong, Denghuang,Li, Jiafeng,Yuan, Chengye,Yuan, Junying
, p. 55 - 66 (2007/10/03)
For the structure-activity relationship, a series of substituted arylsulfonyl-phenylbenzamides is reported.
