Chiral preference of l-tryptophan derived metal-based antitumor agent of late 3d-metal ions (Co(II), Cu(II) and Zn(II)) in comparison to d- and dl-tryptophan analogues: Their in vitro reactivity towards CT DNA, 5′-GMP and 5′-TMP

To evaluate the biological preference of chiral drugs for molecular target DNA, new potential metal-based chemotherapeutic agents 1–3 (a–c) of late 3d-transition metals derived from l form, d form, and dl-tryptophan, respectively were synthesized and thoroughly characterized. Interaction studies of 1–3 (a–c) with CT DNA, 5′GMP and 5′-TMP have been carried out. The results reveal that the extent of DNA binding of l form of copper 2a was greatest in comparison to rest of complexes via electrostatic interaction. This was further confirmed by nuclease activity of 2a with supercoiled pBR322 DNA and it was observed that cleavage reaction involves various oxygen species and superoxide radicals by oxidative cleavage mechanism. The complex 2a exhibited significant antitumor activity against MCF-7 cell line.

Graphical abstractTo evaluate chiral preference of two enantiomeric forms l, d and their racemic counterpart dl-tryptophan, new mononuclear complexes 1–3 were synthesized. They can bind to DNA via electrostatic interaction.Figure optionsDownload full-size imageDownload as PowerPoint slide