title: Piperazic acid derivatives inhibit Gli1 in Hedgehog signaling pathway.
abstract: Piperazic acid, a non-proteinogenic amino acid, found in complex secondary metabolites and peptide natural substances, has shown down regulation of Gli1 expression in Hedgehog signaling pathway in cell based assays. Further structure activity relationship study indicated that amide derivatives of piperazic acid are more potent than piperazic acid itself, with little to no toxicity. However, other cellular components involved in the pathway were not affected. To the best of our knowledge, this is the first report on the inhibitory property of piperazic acid in this pathway. Hence, this molecule could serve as a useful tool for studying Hedgehog signaling.
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
authors.forename: Harleen
authors.initials: H
authors.lastname: Khatra
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Kundu
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
authors.forename: Pragya Paramita
authors.initials: PP
authors.lastname: Khan
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
authors.forename: Indranil
authors.initials: I
authors.lastname: Duttagupta
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India.
authors.forename: Sankha
authors.initials: S
authors.lastname: Pattanayak
authors.affiliation: Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700 032, India. Electronic address: ocss5@iacs.res.in.
authors.forename: Surajit
authors.initials: S
authors.lastname: Sinha
mesh_terms: D000818:Animals; D002460:Cell Line; D053823:Hedgehog Proteins / Q000378:metabolism*; D011724:Pyridazines / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D011724:Pyridazines; D000071676:Zinc Finger Protein GLI1; C014756:piperazic acid
keywords: Gli; Hedgehog signaling; Hedgehog-inhibitors; Piperazic acid; Shh-LIGHT2 cells