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Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest

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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… Click to show full 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.

Keywords: total synthesis; leads cytotoxic; cytotoxic effect; hit leads

Journal Title: ChemMedChem
Year Published: 2020

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