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

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Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest.
ChemMedChem ( IF 3.6 ) Pub Date : 2020-04-21 , DOI: 10.1002/cmdc.202000066
Hans-René Bjørsvik ₁ , Bjørn Tore Gjertsen _{2,

3} , Vijayaragavan Elumalai ₁

Affiliation

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.

中文翻译：

击中导致白血病细胞具有细胞毒性作用的线索：总合成中间体作为分子宝藏。

先前设计和开发的包括[1,1'-联苯] -2-胺和咔唑中间体的12个步骤的全合成方法，最终产生了咔唑生物碱咔唑霉素G，被用作筛选化合物库，目的是鉴定潜在的铅。具有细胞毒性作用的化合物。通过使用涉及两个人类细胞系HL-60和MOLM-13的体外试验研究了这些化合物，它们均模拟急性髓细胞白血病（AML）。在简洁的SAR分析中，将体外生物学测试结果与各种中间体的分子结构一起使用。尽管与两种人类细胞系相比，最终的天然产物卡巴霉素G均未显示出细胞毒性，但几种中间体仍显示出细胞毒性（IC50 <10-4 M）。

更新日期：2020-03-31

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