Synthesis and evaluation of the HIF-1α inhibitory activities of novel ursolic acid tetrazole derivatives.

ID: ALA4392861

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of the HIF-1α inhibitory activities of novel ursolic acid tetrazole derivatives.

Authors: Zhang LH, Zhang ZH, Li MY, Wei ZY, Jin XJ, Piao HR.

Abstract: The hypoxia-inducible factor-1α (HIF-1α) pathway has been implicated in tumor angiogenesis, growth, and metastasis. Therefore, the inhibition of this pathway is an important therapeutic target for the treatment of various types of cancers. Here, we designed and synthesized 31 ursolic acid (UA) derivatives containing a tetrazole moiety and evaluated them for their potential anti-tumor activities as HIF-1α transcriptional inhibitors. Of these, compound 14d (IC₅₀ 0.8 ± 0.2 µM) displayed the most potent activity and compounds 14a (IC₅₀ 4.7 ± 0.2 µM) exhibited the most promising biological profile. Analysis of the structure-activity relationships of these compounds with HIF-1α suggested that the presence of a tetrazole group located at C-28 of the UA derivatives was critical for their inhibitory activities.

CiteXplore: 31006525

DOI: 10.1016/j.bmcl.2019.04.028

Patent ID: ┄