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

Farukh Arjmand; Mohd Muddassir; Rizwan Hasan Khan

doi:10.1016/j.ejmech.2010.04.031

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

Eur J Med Chem. 2010 Sep;45(9):3549-57. doi: 10.1016/j.ejmech.2010.04.031. Epub 2010 May 10.

Authors

Farukh Arjmand¹, Mohd Muddassir, Rizwan Hasan Khan

Affiliation

¹ Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India. [email protected]

PMID: 20537435
DOI: 10.1016/j.ejmech.2010.04.031

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Absorption
Animals
Antineoplastic Agents / chemistry
Antineoplastic Agents / metabolism
Antineoplastic Agents / pharmacology
Cattle
Cell Line, Tumor
Cobalt / chemistry
Copper / chemistry
DNA / chemistry
DNA / metabolism*
Guanosine Monophosphate / metabolism*
Humans
Inhibitory Concentration 50
Metals, Heavy / chemistry*
Nucleic Acid Conformation / drug effects
Organometallic Compounds / chemistry
Organometallic Compounds / metabolism*
Organometallic Compounds / pharmacology*
Spectrum Analysis
Stereoisomerism
Substrate Specificity
Thymidine Monophosphate / metabolism*
Tryptophan / chemistry*
X-Ray Diffraction
Zinc / chemistry

Substances

Antineoplastic Agents
Metals, Heavy
Organometallic Compounds
Thymidine Monophosphate
Cobalt
Copper
Guanosine Monophosphate
Tryptophan
DNA
calf thymus DNA
Zinc