Synthesis and evaluation of biological activities of vibsanin A analogs.

Authors :: Matsuki W
Miyazaki S
Yoshida K
Ogura A
Sasazawa Y
Takao KI
Simizu S
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2017 Oct 01; Vol. 27 (19), pp. 4536-4539. Date of Electronic Publication: 2017 Aug 31.
Publication Year :: 2017
Abstract: Vibsanin A is an 11-membered vibsane diterpenoid and is reported to induce myeloid cell differentiation via activation of protein kinase C (PKC) without tumor-promoting activity. Therefore, vibsanin A is thought to be an attractive compound for acute myeloid leukemia (AML) therapy. In this study, we synthesized vibsanin A analogs and compared the activity of these compounds for PKC activation and myeloid cell differentiation. We found that the hydroxymethyl group in vibsanin A is an important substituent to induce differentiation of AML cells. Collectively, our results showed the biochemical features of vibsanin A and provided new insights into the development of new antileukemic drugs.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)