Design, synthesis and cytotoxic evaluation of β-aryl-α-dimethoxyphosphoryl-γ-lactams

Cinar S., ÜNALEROĞLU C., AK A., Garipcan B.

Medicinal Chemistry Research, vol.26, no.5, pp.1022-1028, 2017 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 5
  • Publication Date: 2017
  • Doi Number: 10.1007/s00044-017-1816-y
  • Journal Name: Medicinal Chemistry Research
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1022-1028
  • Keywords: Chemotherapeutic drugs, In vitro cytotoxic activity, Nitrovinyl arenes, β-Aryl-α-dimethoxyphosphoryl-γ-lactams
  • Ankara Haci Bayram Veli University Affiliated: No

Abstract

© 2017, Springer Science+Business Media New York.New β-aryl-α-dimethoxyphosphoryl-γ-lactams 4a, b were designed and synthesized through the intra-molecular cyclization of 3a, b obtained from the addition reaction of methyl 2-(dimethoxyphosphoryl)acetate to (E)-2-(2-nitrovinyl)thiophene and (E)-2-(2-nitrovinyl)furan, respectively. The in vitro cytotoxicity of these compounds was evaluated against human breast cancer (MCF-7), rat glioblastoma (C6), prostate cancer (PC3), neuroblastoma (SHSY-5Y), and mouse fibroblast cell lines (L929). Dimethyl (4-(furan-2-yl)-2-oxopyrrolidin-3-yl)phosphonate (4b) was found to have cytotoxic activity towards MCF-7 and PC3 cell lines at the concentration values above 5 mM and 6 mM, respectively (IC50 values of MCF-7, 5.92 ± 1.86; PC3, 6.70 ± 2.10 mM). Dimethyl (2-oxo-4-(thiophen-2-yl)pyrrolidin-3-yl)phosphonate (4a) only decreased the viability of MCF-7 cells at 8 mM concentration (IC50 value of MCF-7 5.67 ± 1.70 in mM). In addition 4a, b had shown no significant cytotoxic effect on C6, SHSY-5Y and L929 cell lines.