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Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest
Author(s) -
Bjørsvik HansRené,
Gjertsen Bjørn Tore,
Elumalai Vijayaragavan
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000066
Subject(s) - cytotoxicity , carbazole , natural product , stereochemistry , in vitro , cytotoxic t cell , chemistry , biphenyl , cell culture , amine gas treating , molecule , combinatorial chemistry , biochemistry , biology , organic chemistry , genetics
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 (IC 50 <10 −4 M), although the final natural product carbazomycin G did not reveal cytotoxicity versus the two said human cell lines.