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

• Published in: Chemistry & biodiversity 2019-11, Vol.16 (11), p.e1900375-n/a
• Main Authors: Khan, Rehan, Ulusan, Sinem, Banerjee, Sreeparna, Dogan, Özdemir
• Format: Article
• Language: English
• Subjects: Antibiotics; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; aziridine phosphonic acids; Aziridines - chemical synthesis; Aziridines - chemistry; Aziridines - pharmacology; Cancer; Cell death; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Colon; Colorectal cancer; Colorectal carcinoma; Cytotoxicity; Derivatives; Drug Screening Assays, Antitumor; Etoposide; Humans; Hydrogen; Molecular Structure; monohydrolysis of phosphonates; necrosis; Phosphonates; Phosphonic acids; Phosphorous Acids - chemical synthesis; Phosphorous Acids - chemistry; Phosphorous Acids - pharmacology; Toxicity; Tumor cell lines
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.201900375

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 α‐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.