title: Synthesis and evaluation of new salicylaldehyde-2-picolinylhydrazone Schiff base compounds of Ru(II), Rh(III) and Ir(III) as in vitro antitumor, antibacterial and fluorescence imaging agents.
abstract: Reaction of salicylaldehyde-2-picolinylhydrazone (HL) Schiff base ligand with precursor compounds [{(p-cymene)RuCl2}2] 1, [{(C6H6)RuCl2}2] 2, [{Cp*RhCl2}2] 3 and [{Cp*IrCl2}2] 4 yielded the corresponding neutral mononuclear compounds 5-8, respectively. The in vitro antitumor evaluation of the compounds 1-8 against Dalton's ascites lymphoma (DL) cells by fluorescence-based apoptosis study and by their half-maximal inhibitory concentration (IC50) values revealed the high antitumor activity of compounds 3, 4, 5 and 6. Compounds 1-8 render comparatively lower apoptotic effect than that of cisplatin on model non-tumor cells, i.e., peripheral blood mononuclear cells (PBMC). The antibacterial evaluation of compounds 5-8 by agar well-diffusion method revealed that compound 6 is significantly effective against all the eight bacterial species considered with zone of inhibition up to 35 mm. Fluorescence imaging study of compounds 5-8 with plasmid circular DNA (pcDNA) and HeLa RNA demonstrated their fluorescence imaging property upon binding with nucleic acids. The docking study with some key enzymes associated with the propagation of cancer such as ribonucleotide reductase, thymidylate synthase, thymidylate phosphorylase and topoisomerase II revealed strong interactions between proteins and compounds 5-8. Conformational analysis by density functional theory (DFT) study has corroborated our experimental observation of the N, N binding mode of ligand. Compounds 5-8 exhibited a HOMO (highest occupied molecular orbital)-LUMO (lowest unoccupied molecular orbital) energy gap 2.99-3.04 eV. Half-sandwich ruthenium, rhodium and iridium compounds were obtained by treatment of metal precursors with salicylaldehyde-2-picolinylhydrazone (HL) by in situ metal-mediated deprotonation of the ligand. Compounds under investigation have shown potential antitumor, antibacterial and fluorescence imaging properties. Arene ruthenium compounds exhibited higher activity compared to that of Cp*Rh/Cp*Ir in inhibiting the cancer cells growth and pathogenic bacteria. At a concentration 100 µg/mL, the apoptosis activity of arene ruthenium compounds, 5 and 6 (~30 %) is double to that of Cp*Rh/Cp*Ir compounds, 7 and 8 (~12 %). Among the four new compounds 5-8, the benzene ruthenium compound, i.e., compound 6 is significantly effective against the pathogenic bacteria under investigation.
authors.affiliation: Centre for Advanced Studies in Chemistry, North Eastern Hill University, Shillong, 793 022, India.
authors.forename: Narasinga Rao
authors.initials: NR
authors.lastname: Palepu
authors.forename: S L
authors.initials: SL
authors.lastname: Nongbri
authors.forename: J Richard
authors.initials: JR
authors.lastname: Premkumar
authors.forename: Akalesh Kumar
authors.initials: AK
authors.lastname: Verma
authors.forename: Kaushik
authors.initials: K
authors.lastname: Bhattacharjee
authors.forename: S R
authors.initials: SR
authors.lastname: Joshi
authors.forename: Scott
authors.initials: S
authors.lastname: Forbes
authors.forename: Yurij
authors.initials: Y
authors.lastname: Mozharivskyj
authors.forename: Romita
authors.initials: R
authors.lastname: Thounaojam
authors.forename: K
authors.initials: K
authors.lastname: Aguan
authors.forename: Mohan Rao
authors.initials: MR
authors.lastname: Kollipara
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D007495:Iridium / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011789:Quantum Theory; D012238:Rhodium / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012545:Schiff Bases / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D005456:Fluorescent Dyes; D006835:Hydrazones; D009942:Organometallic Compounds; D012545:Schiff Bases; D007495:Iridium; D012428:Ruthenium; D012238:Rhodium