title: New modulated design and synthesis of chiral CuII/SnIV bimetallic potential anticancer drug entity: in vitro DNA binding and pBR322 DNA cleavage activity.
abstract: A new chiral ligand scaffold L derived from (R)-2-amino-2-phenyl ethanol and diethyl oxalate was isolated and thoroughly characterized by various spectroscopic methods. The ligand L was allowed to react with CuCl(2)·2H(2)O and NiCl(2)·6H(2)O to achieve monometallic complexes 1 and 2, respectively. Subsequently modulation of 1 and 2 was carried out in the presence of SnCl(4)·5H(2)O to obtain heterobimetallic potential drug candidates 3 and 4 possessing (Cu(II)/Sn(IV) and Ni(II)/Sn(IV)) metallic cores, respectively and characterized by elemental analysis and spectroscopic data including (1)H, (13)C and (119)Sn NMR in case of 3 and 4. In vitro DNA binding studies revealed that complex 3 avidly binds to DNA as quantified by K(b) and K(sv) values. Complex 3 exhibits a remarkable DNA cleavage activity (concentration dependent) with pBR322 DNA and the cleavage activity of 3 was significantly enhanced in the presence of activators and follows the order H(2)O(2)>Asc>MPA>GSH. Complex 3 cleave pBR322 DNA via hydrolytic pathway and accessible to major groove of DNA.
authors.affiliation: Department of Chemistry, Aligarh Muslim University (AMU), Aligarh, Uttar Pradesh, India. tsartaj62@yahoo.com
authors.forename: Sartaj
authors.initials: S
authors.lastname: Tabassum
authors.forename: Girish Chandra
authors.initials: GC
authors.lastname: Sharma
authors.forename: Farukh
authors.initials: F
authors.lastname: Arjmand
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D015195:Drug Design; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D006868:Hydrolysis; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013324:Strontium / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D009942:Organometallic Compounds; D003300:Copper; D004247:DNA; D013324:Strontium