title: Synthesis and Evaluation of In Vitro DNA/Protein Binding Affinity, Antimicrobial, Antioxidant and Antitumor Activity of Mononuclear Ru(II) Mixed Polypyridyl Complexes.
abstract: The four novel Ru(II) complexes [Ru(phen)2MAFIP](2+) (1) [MAFIP = 2-(5-(methylacetate)furan-2-yl)-1 H-imidazo[4,5-f] [1, 10]phenanthroline, phen = 1,10-Phenanthroline], [Ru(bpy)2MAFIP](2+) (2) (bpy = 2,2'-bipyridine) and [Ru(dmb)2MAFIP](2+) (3) (dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(hdpa)2MAFIP](2+) (4) (hdpa = 2,2-dipyridylamine) have been synthesized and fully characterized via elemental analysis, NMR spectroscopy, EI-MS and FT-IR spectroscopy. In addition, the DNA-binding behaviors of the complexes 1-4 with calf thymus DNA were investigated by UV-Vis absorption, fluorescence studies and viscosity measurement. The DNA-binding experiments showed that the complexes 1-4 interact with CT-DNA through an intercalative mode. BSA protein binding affinity of synthesized complexes was determined by UV/Vis absorption and fluorescence emission titrations. The binding affinity of ruthenium complexes was supported by molecular docking. The photoactivated cleavage of plasmid pBR322 DNA by ruthenium complexes 1-4 was investigated. All the synthesized compounds were tested for antimicrobial activity by using three Gram-negative (Escherichia coli, Salmonella typhi and Pseudomonas aeruginosa) and three Gram-positive (Micrococcus luteus, Bacillus subtilis and Bacillus megaterium) organisms, these results indicated that complex 3 was more activity compared to other complexes against all tested microbial strains while moderate antimicrobial activity profile was noticed for complex 4. The antioxidant activity experiments show that the complexes exhibit moderate antioxidant activity. The cytotoxicity of synthesized complexes on HeLa cell lines has been examined by MTT assay. The apoptosis assay was carried out with Acridine Orange (AO) staining methods and the results indicate that complexes can induce the apoptosis of HeLa cells. The cell cycle arrest investigated by flow cytometry and these results indicate that complexes 1-4 induce the cell cycle arrest at G0/G1 phase.
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Venkat Reddy
authors.initials: VR
authors.lastname: Putta
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Nagamani
authors.initials: N
authors.lastname: Chintakuntla
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Rajender Reddy
authors.initials: RR
authors.lastname: Mallepally
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Srishailam
authors.initials: S
authors.lastname: Avudoddi
authors.affiliation: Department of Biochemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Nagasuryaprasad
authors.initials: N
authors.lastname: K
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Nancherla
authors.affiliation: Bioengineering and Environmental Sciences, CSIR-Indian Institute of Chemical Technology, Taranaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Yaswanth
authors.initials: Y
authors.lastname: V V N
authors.affiliation: Bioengineering and Environmental Sciences, CSIR-Indian Institute of Chemical Technology, Taranaka, Hyderabad, Telangana State, 500007, India.
authors.forename: Prakasham
authors.initials: P
authors.lastname: R S
authors.affiliation: Department of Biochemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India.
authors.forename: Satyanarayana Singh
authors.initials: SS
authors.lastname: Surya
authors.affiliation: Department of Chemistry, University College of Science, Osmania University, Hyderabad, Telangana State, 500007, India. ssnsirasani@gmail.com.
authors.forename: Satyanarayana
authors.initials: S
authors.lastname: Sirasani
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry / Q000494:pharmacology*; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D000975:Antioxidants; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D010618:Phenanthrolines; D012710:Serum Albumin, Bovine; D012428:Ruthenium; D004247:DNA; C427203:calf thymus DNA
keywords: Antimicrobial activity; Antioxidant; Cytotoxicity; DNA binding; Ru(II) complexes