Crystal structure, DNA binding studies, nucleolytic property and topoisomerase I inhibition of zinc complex with 1,10-phenanthroline and 3-methyl-picolinic acid.
Crystal structure analysis of the zinc complex establishes it as a distorted octahedral complex, bis(3-methylpicolinato-kappa(2) N,O)(2)(1,10-phenanthroline-kappa(2) N,N)-zinc(II) pentahydrate, [Zn(3-Me-pic)(2)(phen)]x5H(2)O. The trans-configuration of carbonyl oxygen atoms of the carboxylate moieties and orientation of the two planar picolinate ligands above and before the phen ligand plane seems to confer DNA sequence recognition to the complex. It cannot cleave DNA under hydrolytic condition but can slightly be activated by hydrogen peroxide or sodium ascorbate. Circular Dichroism and Fluorescence spectroscopic analysis of its interaction with various duplex polynucleotides reveals its binding mode as mainly intercalation. It shows distinct DNA sequence binding selectivity and the order of decreasing selectivity is ATAT > AATT > CGCG. Docking studies lead to the same conclusion on this sequence selectivity. It binds strongly with G-quadruplex with human tolemeric sequence 5'-AG(3)(T(2)AG(3))(3)-3', can inhibit topoisomerase I efficiently and is cytotoxic against MCF-7 cell line.
Seng
Hoi-Ling
HL
Faculty of Engineering and Science, Universiti Tunku Abdul Rahman, 53300, Kuala Lumpur, Malaysia.
Von
Sze-Tin
ST
Tan
Kong-Wai
KW
Maah
Mohd Jamil
MJ
Ng
Seik-Weng
SW
Rahman
Raja Noor Zaliha Raja Abd
RN
Caracelli
Ignez
I
Ng
Chew-Hee
CH
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D053837:DNA Cleavage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008956:Models, Chemical; D008958:Models, Molecular; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry; D010848:Picolinic Acids / Q000737:chemistry; D010957:Plasmids / Q000737:chemistry; D059004:Topoisomerase I Inhibitors; D015032:Zinc / Q000737:chemistry
C548878:3-methylpicolinic acid; D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D009942:Organometallic Compounds; D010618:Phenanthrolines; D010848:Picolinic Acids; D059004:Topoisomerase I Inhibitors; D006861:Hydrogen Peroxide; D004264:DNA Topoisomerases, Type I; D015032:Zinc; D001205:Ascorbic Acid; C025205:1,10-phenanthroline