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Medicinal Chemistry Research

, Volume 24, Issue 7, pp 2825–2837 | Cite as

Synthesis, toxicity and chemo-sensitization of HeLa cells to etoposide, of some 2-methyl amino acid ester-substituted-1,3-benzoxazines

  • Saleh K. Ihmaid
  • Cheree Fitzgibbon
  • Jasim M. A. Al-RawiEmail author
Original Research

Abstract

A number of new L- or LD-2-amino acid ester-(substituted)-benz[1,3]oxazines 1217 were synthesized from the reaction of free L- or LD-amino acid ester 9ad with 2-methylthio-1,3-benzoxazines 11ag. The structures of the new products 1217 were confirmed from their 1H, 13CNMR and IR spectra and CHN microanalysis. Some of these compounds weakly inhibited DNA-PK and platelet aggregation. Studies of the toxicity for some of the new compounds showed mostly no inhibitory effects on HeLa cell growth at 1 and 10 µM and some up to 40 µM. The chemo-sensitization to etoposide by some of the compounds revealed that the most effective chemo-sensitizers at 10 µM were 14c (1.83 fold), 12e (1.42 fold), 15a (0.8 fold), 16d (0.76 fold) and 1c (0.74). However, at 1 µM in the presence of etoposide, some compounds were shown to be more effective. No direct link was observed between the type of the L-amino acid methyl ester as well as the 7-, 8-, or 7, 8-substitution on the aromatic ring on the effectiveness of the chemo-sensitizers; however, the 7-hydroxy group did lower the effective chemo-sensitizers values.

Keywords

2-Amino acid ester-substituted-benz[1,3]oxazines Toxicity Chemo-sensitization to etoposide 

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Saleh K. Ihmaid
    • 1
  • Cheree Fitzgibbon
    • 1
  • Jasim M. A. Al-Rawi
    • 1
    Email author
  1. 1.School of Pharmacy and Applied Science, La Trobe Institute for Molecular ScienceLa Trobe UniversityBendigoAustralia

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