Penthala, Narsimha R. published the artcileAntitumor properties of novel sesquiterpene lactone analogs as NFκB inhibitors that bind to the IKKβ ubiquitin-like domain (ULD), SDS of cas: 6850-57-3, the publication is European Journal of Medicinal Chemistry (2021), 113675, database is CAplus and MEDLINE.
Melampomagnolide B (MMB) is a parthenolide (PTL) based sesquiterpene lactone that has been used as a template for the synthesis of a plethora of lead anticancer agents owing to its reactive C-10 primary hydroxyl group. Such compounds have been shown to inhibit the IKKβ subunit, preventing phosphorylation of the cytoplasmic IκB inhibitory complex. The present study focuses on the synthesis and in vitro antitumor properties of novel benzyl and phenethyl carbamates of MMB. Screening of these MMB carbamates identified analogs with potent growth inhibition properties against a panel of 60 human cancer cell lines (71% of the mols. screened had GI50 values < 2μM). Two analogs, the 4-methoxybenzyl carbamate (I) and the 4-bromophenethyl carbamate, were the most active compounds Lead compound I inhibited cell proliferation in M9 ENL AML cells, and in TMD-231, OV-MD-231 and SUM149 breast cancer cell lines. Interestingly, mechanistic studies showed that I did not inhibit p65 phosphorylation in M9 ENL AML and OV-MD-231 cells, but did inhibit phosphorylation of both p65 and IκBα in SUM149 cells. 4-Methoxybenzyl carbamate also reduced NFκB binding to DNA in both OV-MD-231 and SUM149 cells. Mol. docking studies indicated that I and the 4-bromophenethyl carbamate are both predicted to interact with the ubiquitin-like domain (ULD) of the IKKβ subunit. These data suggest that in SUM149 cells, I is likely acting as an allosteric inhibitor of IKKβ, whereas in M9 ENL AML and OV-MD-231 cells. 4-Methoxybenzyl carbamate is able to inhibit an event after IκB/p65/p50 phosphorylation by IKKβ that leads to inhibition of NFκB activation and reduction in NFκB-DNA binding. The 4-methoxybenzyl carbamate analog I was by far the most potent compound in either carbamate series, and was considered an important lead compound for further optimization and development as an anticancer agent.
European Journal of Medicinal Chemistry published new progress about 6850-57-3. 6850-57-3 belongs to ethers-buliding-blocks, auxiliary class Amine,Benzene,Ether, name is (2-Methoxyphenyl)methanamine, and the molecular formula is C8H11NO, SDS of cas: 6850-57-3.
Referemce:
https://en.wikipedia.org/wiki/Ether,
Ether | (C2H5)2O – PubChem