Enantiomeric pairs of copper(II) polypyridyl-alanine complex salts: anticancer studies

  • Pei Ying Ng
  • Soi Moi Chye
  • Yee Liang Tiong
  • Cheang Wei Chan
  • Kong Wai Tan
  • Ing Hong Ooi
  • Chew Hee Ng
Article

Abstract

The anticancer properties of two previously characterized pairs of optically pure chiral complex salts [Cu(phen)(ala)(H2O)]X·xH2O (phen = 1.10-phenanthroline; X = NO3; ala: l-alanine (l-ala) 1 and d-alanine (d-ala) 2; and (X = Cl; ala: l-ala, 3 and d-ala, 4; x = number of lattice water molecules) are reported herein, together with the crystal structure of the d-enantiomer 4. Unlike cisplatin which is ineffective against MCF-7 cancer cells with the absence of caspase-3 protein expression, these two pairs of complex salts were effective against this cell line and they were able to induce an increase in intracellular ROS, loss in mitochondrial membrane potential, cell cycle arrest mainly at SubG1 phase , caspase-9 activation, and caspase-3/caspase-7-independent apoptosis. Screening of 1 on the NCI-60 panel of human cancer cell lines showed that it was effective against most of the cell lines. MTT-NCI modified assay screening was also done on other cancer cell lines, viz. A549, CNE1, and HepG2, and two normal cell lines, viz. MCF-10A and CHANG. The effects of chirality of these Cu(II) compounds, especially the greater selectivity of d-enantiomers over the l-counterparts, on their anticancer properties are also reported herein.

Notes

Acknowledgements

The authors would like to thank the Malaysian Ministry of Science, Technology and Innovation (MOSTI) for the eScience Grant (No. 02-02-09-SF0036) used for sponsoring this research. Tan KW wished to thank Dr. Low Yun Yee for useful discussion on revising the cif file.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11243_2018_234_MOESM1_ESM.docx (616 kb)
Supplementary material 1 (DOCX 615 kb)

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Authors and Affiliations

  1. 1.School of Health SciencesInternational Medical UniversityKuala LumpurMalaysia
  2. 2.Department of ChemistryUniversity of MalayaKuala LumpurMalaysia
  3. 3.Pharmaceutical Chemistry Department, School of PharmacyInternational Medical UniversityKuala LumpurMalaysia

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