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Synthesis of α-santonin derivatives for diminutive effect on T and B-cell proliferation and their structure activity relationships.
European Journal of Medicinal Chemistry 2017 Februrary 16
A new library of 20 compounds from α-santonin was synthesized and tested against Con-A induced T-cell proliferation and LPS-induced B-cell proliferation via MTT assay. The study resulted in the identification of potent immunosuppressant molecules, which were further screened along with α-santonin for Tumor Necrosis Factor Alpha (TNF-α) inhibitory activity. One of the molecules (7) at 10 μM showed equipotency to that of dexamethasone (1 μM conc.) used as a standard. Structure activity relationships of the synthesized compounds along with our earlier reported α-santonin derivatives have been studied. Inferences from the modifications carried out at all the three sites of α-santonin have been elaborated. Computational study of the active compounds shows TNF-α protein as its preferable target rather than Inosine Monophosphate Dehydrogenase (IMPDH).
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