Leucettamine B analogs and their carborane derivative as potential anti-cancer agents: Design, synthesis, and biological evaluation

Ming Hua Hsu, Cheng Ying Hsieh, Mohit Kapoor, Jui Hsun Chang, Hsueh Liang Chu, Tsai Mu Cheng, Kai Cheng Hsu, Tony Eight Lin, Fu Yuan Tsai, Jia Cherng Horng

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Abstract

Leucettamine B is a natural product found in marine sponge Leucetta microraphis. Several of analogs of its family, such as aplysinopsine and clathridine, are medicinally active molecules which have applications in many pharmaceuticals and healthcare products; however, thus far, leucettamine B has not been studied. In this report, we describe the synthesis of a new class of analogs of leucettamine B obtained by Knoevenagel condensation using a microwave reactor. The 25 newly synthesized compounds were tested against MDA-MB-468, SW480, and Mahlavu cell lines for anticancer activity. Among them, the carborane-based compound (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(1-closo-carboranyl)-2-thioxo -thiazolidin-4-one (49) and (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(2-(pyrrolidin-1-yl)ethyl)-2-thioxothiazolidin-4-one (31) derivatives were found to have the most potential for use against tumor cells. The carborane derivative 49 had the lowest IC50 value against the SW480 cell line (4.7 μM) and the Mahlavu (6.6 μM) cell line. Furthermore, compound 31 also had a low IC50 value against SW480 (7.5 μM). Our research shows that leucettamine B analogs might have potential for use in cancer chemotherapy.

Original languageEnglish
Article number103729
JournalBioorganic Chemistry
Volume98
DOIs
Publication statusPublished - 2020 May

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this

Hsu, M. H., Hsieh, C. Y., Kapoor, M., Chang, J. H., Chu, H. L., Cheng, T. M., Hsu, K. C., Lin, T. E., Tsai, F. Y., & Horng, J. C. (2020). Leucettamine B analogs and their carborane derivative as potential anti-cancer agents: Design, synthesis, and biological evaluation. Bioorganic Chemistry, 98, [103729]. https://doi.org/10.1016/j.bioorg.2020.103729