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.
Department of Chemistry, Aligarh Muslim University, Aligarh-202002, India. farukh_arjmand@yahoo.co.in
Farukh
F
Arjmand
Mohd
M
Muddassir
Rizwan Hasan
RH
Khan
D000042:Absorption; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002417:Cattle; D045744:Cell Line, Tumor; D003035:Cobalt / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D019216:Metals, Heavy / Q000737:chemistry*; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D013057:Spectrum Analysis; D013237:Stereoisomerism; D013379:Substrate Specificity; D013938:Thymidine Monophosphate / Q000378:metabolism*; D014364:Tryptophan / Q000737:chemistry*; D014961:X-Ray Diffraction; D015032:Zinc / Q000737:chemistry
D000970:Antineoplastic Agents; D019216:Metals, Heavy; D009942:Organometallic Compounds; D013938:Thymidine Monophosphate; D003035:Cobalt; D003300:Copper; D006157:Guanosine Monophosphate; D014364:Tryptophan; D004247:DNA; C427203:calf thymus DNA; D015032:Zinc