Synthesis, Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives

Khan R., ULUSAN S., BANERJEE S., DOĞAN Ö.

CHEMISTRY & BIODIVERSITY, vol.16, no.11, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 16 Issue: 11
  • Publication Date: 2019
  • Doi Number: 10.1002/cbdv.201900375
  • Journal Name: CHEMISTRY & BIODIVERSITY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: aziridine phosphonic acids, monohydrolysis of phosphonates, cytotoxicity, apoptosis, necrosis, 2-AZIRIDINYL PHOSPHONATES, INHIBITORS, APOPTOSIS, DESIGN, ANALOG
  • Middle East Technical University Affiliated: Yes

Abstract

New aziridine 2-phosphonic acids were prepared by monohydrolysis of the aziridine 2-phosphonates that were obtained by the modified Gabriel-Cromwell reaction of vinyl phosphonate or alpha-tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT-116 colorectal cancer cell lines and the CCD-18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)-1-[(1S)-1-(naphthalen-2-yl)ethyl]aziridin-2-yl}phosphonate), 2h (ethyl hydrogen (1-benzylaziridin-2-yl)phosphonate), and 2i (ethyl hydrogen (1-cyclohexylaziridin-2-yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well-known apoptosis inducing agent.