Hit to Leads with Cytotoxic Effect in Leukemic Cells: Total Synthesis Intermediates as a Molecule Treasure Chest. (21st April 2020)

• Record Type: Journal Article
• Authors: Bjørsvik, Hans‐René; Gjertsen, Bjørn Tore; Elumalai, Vijayaragavan
• Is Part Of: ChemMedChem. Volume 15:Number 10(2020)
• Page Start: 862
• Page End: 870
• Publication Date: 2020-04-21
• Subjects: carbazole alkaloids -- cytotoxicity -- HL-60 -- leukemia -- MOLM-13; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000066
• Languages: English
• ISSNs: 1860-7179

Abstract

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. Abstract : Deadlier than the parent : A 12‐step synthetic pathway that includes [1, 1′‐biphenyl]‐2‐amine and carbazole intermediates that ultimately leads to the naturally occurring carbazole alkaloid carbazomycin G was used to generate a compound library aimed at screening for leads that possess cytotoxic effect against the two human cell lines HL‐60 and MOLM‐13.