Novel derivatives of ISO-1 as potent inhibitors of MIF biological function.
A series of novel 1,2,4-oxadiazole, phthalimide, amide and other derivatives of ISO-1 were synthesized and probed for inhibition of macrophage migration inhibitory factor (MIF) activity. Several compounds inhibited MIF enzymatic activity at levels better than ISO-1. Of note, compounds 7, 22, 23, 24, 25 and 27 inhibited the spontaneous secretion/release/recognition of MIF from freshly isolated human peripheral blood mononuclear cells and, more importantly, inhibited the MIF-induced production of interleukin-6 (IL-6) and/or interleukin-1beta (IL-1beta) significantly better than ISO-1.
Balachandran
Sarala
S
Department of Medicinal Chemistry, Piramal Life Sciences, Off Western Express Highway, Goregaon (E), Mumbai 400 063, India. sarala.balachandran@piramal.com
Rodge
Atish
A
Gadekar
Pradip K
PK
Yadav
Vitthal N
VN
Kamath
Divya
D
Chetrapal-Kunwar
Anshu
A
Bhatt
Pooja
P
Srinivasan
Shaila
S
Sharma
Somesh
S
Vishwakarma
Ram A
RA
Dagia
Nilesh M
NM
D000577:Amides / Q000737:chemistry; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010069:Oxadiazoles / Q000737:chemistry; D010797:Phthalimides / Q000737:chemistry; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000378:metabolism
C462499:3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazoleacetic acid methyl ester; D000577:Amides; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D007555:Isoxazoles; D010069:Oxadiazoles; D010797:Phthalimides; D011971:Receptors, Immunologic; C033184:macrophage migration inhibitory factor receptor; C037431:phthalimide