Synthesis of a rhodanine-based compound library targeting Bcl-XL and Mcl-1

A small library of pyridine-based rhodanine analogues of BH3I-1 were synthesized and screened against B-cell lymphoma-extra large (Bcl-XL) and myeloid cell leukemia sequence 1 (Mcl-1) for the ability to displace 5-carboxyfluorescein-labeled Bak peptide (Flu-Bak). Differences in selectivity toward Bcl-XL and Mcl-1 were observed, and the bind- ing modes of selected compounds were studied further. The results may be useful in design- ing potent small-molecule inhibitors of Bcl-XL and Mcl-1 as well as selective Mcl-1 inhibitors.