CrossRef enabled

PAC Archives

Archive →

Pure Appl. Chem., 2011, Vol. 83, No. 3, pp. 723-731

Published online 2011-02-05

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

Paul H. Bernardo1*, Thirunavukkarasu Sivaraman2, Kah-Fei Wan3, Jin Xu1, Janarthanan Krishnamoorthy4, Chun Meng Song5, Liming Tian1, Jasmine S. F. Chin1, Diane S. W. Lim1, Henry Y. K. Mok4, Victor C. Yu6, Joo Chuan Tong7,5 and Christina L. L. Chai6,1*

1 Institute of Chemical and Engineering Sciences, Agency for Science Technology and Research (A*STAR), 8 Biomedical Grove, #07-01 Neuros 138632, Singapore
2 School of Chemical and Biotechnology, SASTRA University, Thanjavur-613401, TN, India
3 Novartis Institute for Tropical Diseases, 10 Biopolis Road, #05-01 Chromos 138670, Singapore
4 Department of Biological Sciences, National University of Singapore, 117543, Singapore
5 Institute for Infocomm Research, A*STAR, 1 Fusionopolis Way, No. 21-01 Connexis 138632, Singapore
6 Department of Pharmacy, Faculty of Science, National University of Singapore, 117543, Singapore
7 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, 117597 Singapore

Abstract: 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 binding modes of selected compounds were studied further. The results may be useful in designing potent small-molecule inhibitors of Bcl-XL and Mcl-1 as well as selective Mcl-1 inhibitors.