Abstract:
:Group IIA secreted phospholipase A₂ (GIIA sPLA₂) is a member of the mammalian sPLA₂ enzyme family and is associated with various inflammatory conditions. In this study, the synthesis of 2-oxoamides based on α-amino acids and the in vitro evaluation against three secreted sPLA₂s (GIIA, GV and GX) are described. The long chain 2-oxoamide GK126 based on the amino acid (S)-leucine displayed inhibition of human and mouse GIIA sPLA₂s (IC₅₀ 300nM and 180nM, respectively). It also inhibited human GV sPLA₂ with similar potency, while it did not inhibit human GX sPLA₂. The elucidation of the stereoelectronic characteristics that affect the in vitro activity of these compounds was achieved by using a combination of simulated annealing to sample low-energy conformations before the docking procedure, and molecular docking calculations.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Mouchlis VD,Magrioti V,Barbayianni E,Cermak N,Oslund RC,Mavromoustakos TM,Gelb MH,Kokotos Gdoi
10.1016/j.bmc.2010.12.030subject
Has Abstractpub_date
2011-01-15 00:00:00pages
735-43issue
2eissn
0968-0896issn
1464-3391pii
S0968-0896(10)01121-1journal_volume
19pub_type
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