Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest |
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Authors: | Prof. Dr. Hans-René Bjørsvik Prof. Dr. Bjørn Tore Gjertsen Dr. Vijayaragavan Elumalai |
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Affiliation: | 1. Department of Chemistry, University of Bergen, Allégaten 41, 5007 Bergen, Norway;2. Center for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway |
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Abstract: | A previously designed and developed 12-step total synthesis that includes [1,1′-biphenyl]-2-amine and carbazole intermediates and that ultimately produces the carbazole alkaloid carbazomycin G was exploited as a screening compound library with the goal of identifying potential lead compound(s) with cytotoxic effect. These compounds were investigated by using in-vitro tests involving the two human cell lines HL-60 and MOLM-13, which both model acute myeloid leukaemia (AML). The in-vitro biological test results were used together with the molecular structures of the various intermediates in a concise SAR analysis. Several of the intermediates revealed cytotoxicity (IC50<10−4 M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines. |
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Keywords: | carbazole alkaloids cytotoxicity HL-60 leukemia MOLM-13 |
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