ascorbic-acid and 4-cymene

Anticancer active metal complexes with biologically active ligands have the potential to interact with more than one biological target, which could help to overcome acquired and/or intrinsic resistance of tumors to small molecule drugs. In this paper we present the preparation of 2-hydroxy-[1,4]-naphthoquinone-derived ligands and their coordination to a Ru(II)(η(6)-p-cymene)Cl moiety. The synthesis of oxime derivatives resulted in the surprising formation of nitroso-naphthalene complexes, as confirmed by X-ray diffraction analysis. The compounds were shown to be stable in aqueous solution but reacted with glutathione and ascorbic acid rather than undergoing reduction. One-electron reduction with pulse radiolysis revealed different behavior for the naphthoquinone and nitroso-naphthalene complexes, which was also observed in in vitro anticancer assays.

Topics: Antineoplastic Agents; Ascorbic Acid; Cell Line, Tumor; Cell Survival; Coordination Complexes; Cymenes; Drug Resistance, Neoplasm; Glutathione; Humans; Monoterpenes; Naphthoquinones; Ruthenium

The relative affinity of the cationic triangular metallaprism, [(pCH(3)C(6)H(4)Pr(i))(6)Ru(6)(tpt)(2)(dhbq)(3)](6+) ([1](6+)), for various amino acids, ascorbic acid, and glutathione (GSH) has been studied at 37 °C in aqueous solutions at pD 7, using NMR spectroscopy and electrospray ionization mass spectrometry (ESI-MS). The metallaprism [1](6+), which is constituted of six (pCH(3)C(6)H(4)Pr(i))Ru corners bridged by three 1,4-benzoquinonato (dhbq) ligands and connected by two 2,4,6tri(pyridin4yl)1,3,5-triazine (tpt) triangular panels, disassembled in the presence of Arg, His, and Lys, while it remains intact with Met. Coordination to the imidazole nitrogen atom in His or to the basic NH/NH(2) groups in Arg and Lys displaces the dhbq and tpt ligands from the (p-cymene)Ru units, and subsequent coordination to the amino and carboxylato groups forms stable N,N,O metallacycles. The binding to amino acids proceeds rapidly, as determined by NMR spectroscopy. Interestingly, solutions of [1](6+) are able to catalyze oxidation of the thiol group of Cys and GSH to give the corresponding disulfides and of ascorbic acid to give the corresponding dehydroascorbic acid. Competition experiments with Arg, Cys, His, and Lys show the simultaneous formation of one single adduct, the (p-cymene)Ru-His complex, and oxidation of Cys to cystine. Furthermore, the (p-cymene)Ru-His complex formed upon the addition of His to [1][CF(3)SO(3)](6) is able to oxidize Cys to cystine much more efficiently than [1](6+). These results provide evidence against interaction with proteins as process in the release of encapsulated guest molecules. Oxidation of Cys and GSH to give the corresponding disulfides may explain the in vitro anticancer activity of [1](6+).

Topics: Amino Acids; Antineoplastic Agents; Arginine; Ascorbic Acid; Cymenes; Cysteine; Disulfides; Glucose; Glutathione; Ligands; Lysine; Magnetic Resonance Spectroscopy; Methionine; Monoterpenes; Organomercury Compounds; Oxidation-Reduction; Ruthenium; Solutions; Spectrometry, Mass, Electrospray Ionization; Sulfhydryl Compounds

In the present study, essential oil from the leaves of Syrian oreganum [Origanum syriacum L. (Lauraceae)] grown in Turkish state forests of the Dortyol district, Turkey, was obtained by steam distillation. The chemical composition of oil was analysed by GC and GC-MS, and was found to contain 49.02% monoterpenes, 36.60% oxygenated monoterpenes and 12.59% sesquiterpenes. The major components are as follows: gamma-terpinene, carvacrol, p-cymene and beta-caryophyllene. Subsequently, the reducing power, antioxidant and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activities of the essential oil were studied. The reducing power was compared with ascorbic acid, and the other activities were compared with 2,6-di-tert-butyl-4-methyl phenol (BHT, butylated hydroxytoluene). The results showed that the activities were concentration dependent. The antioxidant activities of the oil were slightly lower than those of ascorbic acid or BHT, so the oil can be considered an effective natural antioxidant. Antimicrobial activities of the essential oil from the leaves of Origanum syriacum was also determined on 16 microorganisms tested using the agar-disc diffusion method, and showed antimicrobial activity against 13 of these.

Topics: Ampicillin; Anti-Infective Agents; Antioxidants; Ascorbic Acid; Biphenyl Compounds; Cyclohexane Monoterpenes; Cymenes; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Escherichia coli; Free Radical Scavengers; Klebsiella pneumoniae; Micrococcus luteus; Monoterpenes; Nystatin; Oils, Volatile; Origanum; Picrates; Plant Leaves; Plant Oils; Plants, Medicinal; Polycyclic Sesquiterpenes; Sesquiterpenes; Staphylococcus aureus; Streptomycin; Turkey