Structural and biological properties of ortho-quinones having nitrogen-sulfur fuctionalities and their metal conjugates

The preparation and characterization of the thiosemicarbazones (TSC) of three classes of ortho-quinone ligands, viz. 1,2-naphthoquinone, 4-substituted 1,2-naphthaquinone and 9,10-phenanthraquinone are reported...All the synthesized compounds were evaluated for their antiproliferation activities against human breast cancer cell lines --Abstract, page iii

Gadolinium Triflate Immobilized in Imidazolium Based Ionic Liquids: A Recyclable Catalyst and Green Solvent for Acetylation of Alcohols and Amines

Gadolinium triflate immobilized in room temperature ionic liquids (RTIL) 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim][BF4]) and 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6]) was found to be a recyclable and green catalyst for acetylation of a variety of alcohols, phenols and amines. Acetylation reactions using acetic anhydride (Ac2O) as the reagent proceeded in excellent yields in the presence of catalytic amounts (0.2-0.5 mol%) of Gd(OTf)3 immobilized in RTILs, at ambient temperature. In addition, the catalyst system Gd(OTf) 3/[bmim][X] can be recovered and reused efficiently in these transformations

Nickel (II) Complexes of Naphthaquinone Thiosemicarbazone and Semicarbazone: Synthesis, Structure, Spectroscopy, and Biological Activity

Ni(II) complexes of ortho-naphthaquinone thiosemicarbazone and semicarbazone were synthesized and spectroscopically characterized. the X-ray crystal structure of both the complexes describe a distorted octahedral coordination with two tridentate mono-deprotonated ligands. in vitro anticancer studies on MCF-7 human breast cancer cells reveal that the semicarbazone derivative along with its nickel complex is more active in the inhibition of cell proliferation than the thiosemicarbazone analogue

Antitumor Metallothiosemicarbazonates: Structure and Antitumor Activity of Palladium Complex of Phenanthrenequinone Thiosemicarbazone

The crystal structure of the potential antitumor metal compound, viz. chloro, mono(phenanthrenequinone thiosemicarbazonato) palladium(II) dimethyl formamide solvate, is reported. The central palladium(II) atom is in a square planar environment provided by the tridentate, monoanionic thiosemicarbazone ligand and the ancillary chloride ion. The compound exhibited remarkable activity against drug-sensitive and drug-resistant breast cancer cell lines and was relatively nontoxic toward the normal mammary epithelial cells. The drug-induced killing effect against breast cancer cell lines was predominantly mediated via apoptosis, a physiologic form of cell death

Copper Conjugates of Nimesulide Schiff Bases Targeting VEGF, COX and Bcl-2 in Pancreatic Cancer Cells

Copper conjugates of Schiff base derivatives of nimesulide (1), a well-known cyclooxygenase-2 (COX-2) inhibitor, were synthesized, structurally characterized and evaluated for their COX selectivity indices and cytotoxicities on pancreatic tumor, BxPC-3 (COX-2 positive) and MiaPaCa (COX-2 negative) cell lines. Copper conjugates exhibit distorted square planar geometries as revealed by the single crystal X-ray structure determination of Cu(L1)2 and show significant growth inhibition in both cell lines (IC50 values 3-26 µM for COX-2 positive and 5-9 µM for COX-2 negative cell line) than the parent nimesulide (35 µM for COX-2 positive and \u3e100 µM for COX-2 negative cell line). The mechanistic pathway for the biological activity involves inhibition of vascular endothelial growth factor (VEGF) and COX inhibition, as well as down regulation of antiapoptotic Bcl-2 and Bcl-XL proteins

New Nanomedicine Approaches Using Gold-thioguanine Nanoconjugates as Metallo-Ligands

Gold-thioguanine nanoconjugates (AuNP-TG) of size 3-4 nm were synthesized and the ratio between gold and 6-thioguanine (TG) was estimated as ~1:1.5 using a cyanide digestion method and confirmed by flame atomic absorption spectroscopic analysis. AuNP-TG constructs showed high in vitro stability under different pH conditions and biologically relevant solutions for a period of 24 h. Reaction of AuNP-TG with europium or platinum salts resulted in the formation of organized self-assembled metallo-networks

Gold Nanoparticle Based Immunostrip Assay Method for Detection of Protein-A

We have successfully developed gold nanoparticle based immunostrip assay to detect protein-A (PA). Rabbit polyclonal antibody IGg (αPA) that has affinity to PA was conjugated to gold nanoparticles (GNPs) and the gold nanoconjugate (αPA-GNP) was used to detect protein-A by simple immunostrip assay method. ELISA experiments were used to confirm the retention of binding affinity of antibody towards protein-A after conjugation with gold nanoparticles

The Cytotoxicity and Mechanisms of 1,2-naphthoquinone Thiosemicarbazone and Its Metal Derivatives against Mcf-7 Human Breast Cancer Cells

We have investigated the antitumor functions and mechanisms of 1,2-naphthoquinone-2-thiosemicarbazone (NQTS) and its metal complexes (Cu 2+, Pd2+, and Ni2+) against MCF-7 human breast cancer cells. The cells were dosed with these complexes at varying concentrations, and cell viability was measured by a sulforhodamine B (SRB) method. To study mechanisms of action, the complexes were incubated with topoisomerase II (topo II) and supercoiled DNA, linear DNA, nicked open DNA, and relaxed DNA were detected by agarose gel electrophoresis. The results revealed that these complexes are effective antitumor chemicals in inhibiting MCF-7 cell growth, with Ni-NQTS being the most effective among the complexes studied. Our data also indicated that Ni-NQTS is more effective than the commercial antitumor drug, etoposide, based on IC50 values. The mechanistic study of action showed that metal complexes of NQTS, NQ, and NQTS can only stabilize the single-strand nicked DNA, but not double-strand breakage intermediates. In addition, metal derivatives of these ligands, but not the parent NQ and NQTS, exerted an antagonizing effect on topoisomerase II activity. In summary, chemicals with or without metal derivatives might possess different chemical-topoisomerase II-DNA interactions

Design and Development of a Field Applicable Gold Nanosensor for the Detection of Luteinizing Hormone

In this paper, we describe a novel strategy for the fabrication of a nanosensor for detecting luteinizing hormone (LH) of sheep using a gold nanoparticle-peptide conjugate. A new peptide sequence CDHPPLPDILFL (leutinizing hormone peptide, LHP) has been identified, using BLAST and Clustal W analysis, to detect antibody of LH (sheep). LHP has been synthesized and characterized, and their affinity toward anti-LH was established using enzyme linked immunosorbant assay (ELISA) technique. The thiol group in LHP directly binds with gold nanoparticles (AuNPs) to yield AuNP-LHP construct. Detailed physicochemical analysis of AuNP-LHP construct was determined using various analytical techniques. Nanosensor using gold nanoparticle peptide conjugate was developed on the basis of competitive binding of AuNP-LHP and LH toward anti-LH. Nitrocellulose membrane, precoated with anti-LH, was soaked in the mixture of AuNP-LHP and sample of analysis (LH). In the absence of LH (sheep), anti-LH coated on the membrane binds with AuNP-LHP, leading to a distinctive red color, while in the presence of LH, no color appeared in the membrane due to the interaction of anti-LH with LH thereby preventing the binding of AuNP-LHP with membrane bound anti-LH. The sensor assay developed in this study can detect LH (sheep) up to a minimal concentration of ~50 ppm with a high degree of reproducibility and selectivity. The gold-nanoparticle-peptide based nanosensor would be a simple, portable, effective, and low cost technique for infield applications

Neutral Dimeric Copper-Sparfloxacin Conjugate Having Butterfly Motif with Antiproliferative Effects against Hormone Independent BT20 Breast Cancer Cell Line

A neutral dimeric copper conjugate of sparfloxacin and its phenanthroline adduct show considerable enhancement in their antiproliferative activities against hormone independent BT20 breast cancer cells