title: Synthesis, Characterization, and Biological Activities of Pendant Arm-Pyridyltetrazole Copper(II) Complexes: DNA Binding/Cleavage Activity and Cytotoxic Studies.
abstract: 2-(1H-Tetrazol-5-yl)pyridine (L) has been reacted separately with Me2NCH2CH2Cl⋅HCl and ClCH2CH2OH to yield two regioisomers in each case, N,N-dimethyl-2-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]ethanamine (L1)/N,N-dimethyl-2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanamine (L2) and 2-[5-(pyridin-2-yl)-1H-tetrazol-1-yl]ethanol (L3)/2-[5-(pyridin-2-yl)-2H-tetrazol-2-yl]ethanol (L4), respectively. These ligands, L1-L4, have been coordinated with CuCl2 ⋅H2O in 1 : 1 composition to furnish the corresponding complexes 1-4. EPR Spectra of Cu complexes 1 and 3 were characteristic of square planar geometry, with nuclear hyperfine spin 3/2. Single X-ray crystallographic studies of 3 revealed that the Cu center has a square planar structure. DNA binding studies were carried out by UV/VIS absorption; viscosity and thermal denaturation studies revealed that each of these complexes are avid binders of calf thymus DNA. Investigation of nucleolytic cleavage activities of the complexes was carried out on double-stranded pBR322 circular plasmid DNA by using a gel electrophoresis experiment under various conditions, where cleavage of DNA takes place by oxidative free-radical mechanism (OH(⋅)). In vitro anticancer activities of the complexes against MCF-7 (human breast adenocarcinoma) cells revealed that the complexes inhibit the growth of cancer cells. The IC50 values of the complexes showed that Cu complexes exhibit comparable cytotoxic activities compared to the standard drug cisplatin.
authors.affiliation: Department of Chemistry, GITAM University Hyderabad campus, Hyderabad 502329, India.
authors.forename: Shaik
authors.initials: S
authors.lastname: Mustafa
authors.affiliation: Department of Inorganic and Analytical Chemistry, Andhra University, Visakhapatnam, India.
authors.forename: Bommuluri Umamaheswara
authors.initials: BU
authors.lastname: Rao
authors.affiliation: Department of Chemistry, GITAM University Hyderabad campus, Hyderabad 502329, India. manabolu@gmail.com.
authors.forename: Manubolu Surya
authors.initials: MS
authors.lastname: Surendrababu
authors.affiliation: Department of Biotechnology, Gokaraju Rangaraju Institute of Technology, Hyderabad, India.
authors.forename: Kalidindi Krishnam
authors.initials: KK
authors.lastname: Raju
authors.affiliation: Department of Inorganic and Analytical Chemistry, Andhra University, Visakhapatnam, India.
authors.forename: Gollapalli Nageswara
authors.initials: GN
authors.lastname: Rao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D053837:DNA Cleavage; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D013777:Tetrazoles; D003300:Copper; D004247:DNA; C427203:calf thymus DNA
keywords: Copper complexes; Cytotoxic activity; DNA binding; Pendant arm; Pyridyltetrazoles