title: Synthesis and biological activity of novel MIF antagonists.
abstract: Two series of novel furan and indole compounds were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds from both series inhibited the enzymatic activity of MIF at levels equal to or significantly better than ISO-1 (an early MIF inhibitor). The majority of the compounds that robustly inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells were from the furan series (compounds 5, 9, 13, 15, and 16). In contrast, compounds that markedly inhibited the MIF-induced production of pro-inflammatory cytokines were predominantly from the indole series (compounds 26, 29, and 32).
authors.affiliation: Department of Medicinal Chemistry, Piramal Life Sciences, Goregaon (E), Mumbai, India. sarala.balachandran@piramal.com
authors.forename: Sarala
authors.initials: S
authors.lastname: Balachandran
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Gadekar
authors.forename: Santosh
authors.initials: S
authors.lastname: Parkale
authors.forename: Vitthal N
authors.initials: VN
authors.lastname: Yadav
authors.forename: Divya
authors.initials: D
authors.lastname: Kamath
authors.forename: Sneha
authors.initials: S
authors.lastname: Ramaswamy
authors.forename: Somesh
authors.initials: S
authors.lastname: Sharma
authors.forename: Ram A
authors.initials: RA
authors.lastname: Vishwakarma
authors.forename: Nilesh M
authors.initials: NM
authors.lastname: Dagia
mesh_terms: D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D015394:Molecular Structure
chemical_list: D004791:Enzyme Inhibitors; D005663:Furans; D008263:Macrophage Migration-Inhibitory Factors