Comparative solution and structural studies of half-sandwich rhodium and ruthenium complexes bearing curcumin and acetylacetone

Half-sandwich organometallic complexes of curcumin are extensively investigated as anticancer compounds.Speciation studies were performed to explore the solution stability of curcumin complexes formed with [Rh(η5- C5Me5)(H2O)3]2+. Acetylacetone (Hacac), as the simplest β-diketone ligand bearing (O,O) donor set, was involved for comparison and its Ru(η6‑p‑cymene), Ru(η6‑toluene) complexes were also studied. 1H NMR, UV–visible and pH-potentiometric titrations revealed a clear trend of stability constants of the acac complexes: Ru(η6‑p‑cymene) > Ru(η6‑toluene) > Rh(η5-C5Me5). Despite this order, the highest extent of complex formation is seen for the Rh(η5-C5Me5) complexes at pH 7.4. Formation constant of [Rh(η5-C5Me5)(H2curcumin) (H2O)]+ reveals similar solution stability to that of the acac complex. Additionally, structures of two complexes were determined by X-ray crystallography. The in vitro cytotoxicity of curcumin was not improved by the complexation with these organometallic cations.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/2875]This is the peer-reviewed version of the following article: Meszaros, J. P.; Poljarević, J.; Gal, T. G.; May, N. V.; Spengler, G.; Enyedy, E. A. Comparative Solution and Structural Studies of Half-Sandwich Rhodium and Ruthenium Complexes Bearing Curcumin and Acetylacetone. Journal of Inorganic Biochemistry 2019, 195, 91–100. [https://doi.org/10.1016/j.jinorgbio.2019.02.015

Supplementary data for the article: Meszaros, J. P.; Poljarević, J.; Gal, T. G.; May, N. V.; Spengler, G.; Enyedy, E. A. Comparative Solution and Structural Studies of Half-Sandwich Rhodium and Ruthenium Complexes Bearing Curcumin and Acetylacetone. Journal of Inorganic Biochemistry 2019, 195, 91–100. https://doi.org/10.1016/j.jinorgbio.2019.02.015

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2019.02.015]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2873

Supplementary data for the article: Poljarević, J. M.; Tamás Gál, G.; May, N. V.; Spengler, G.; Dömötör, O.; Savić, A. R.; Grgurić-Šipka, S.; Enyedy, É. A. Comparative Solution Equilibrium and Structural Studies of Half-Sandwich Ruthenium(II)(η 6 -Toluene) Complexes of Picolinate Derivatives. J. Inorg. Biochem. 2018, 181, 74–85. https://doi.org/10.1016/j.jinorgbio.2017.12.017

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.12.017]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2119

Supplementary data for the article: Meszaros, J. P.; Poljarević, J.; Gal, T. G.; May, N. V.; Spengler, G.; Enyedy, E. A. Comparative Solution and Structural Studies of Half-Sandwich Rhodium and Ruthenium Complexes Bearing Curcumin and Acetylacetone. Journal of Inorganic Biochemistry 2019, 195, 91–100. https://doi.org/10.1016/j.jinorgbio.2019.02.015

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2019.02.015]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2873

Supplementary data for the article: Poljarević, J. M.; Tamás Gál, G.; May, N. V.; Spengler, G.; Dömötör, O.; Savić, A. R.; Grgurić-Šipka, S.; Enyedy, É. A. Comparative Solution Equilibrium and Structural Studies of Half-Sandwich Ruthenium(II)(η 6 -Toluene) Complexes of Picolinate Derivatives. J. Inorg. Biochem. 2018, 181, 74–85. https://doi.org/10.1016/j.jinorgbio.2017.12.017

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.12.017]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2119

Antiviral, antimicrobial and antibiofilm activity of selenoesters and selenoanhydrides

Selenoesters and the selenium isostere of phthalic anhydride are bioactive selenium compounds with a reported promising activity in cancer, both due to their cytotoxicity and capacity to reverse multidrug resistance. Herein we evaluate the antiviral, the biofilm inhibitory, the antibacterial and the antifungal activities of these compounds. The selenoanhydride and 7 out of the 10 selenoesters were especially potent antiviral agents in Vero cells infected with herpes simplex virus-2 (HSV-2). In addition, the tested selenium derivatives showed interesting antibiofilm activity against Staphylococcus aureus and Salmonella enterica serovar Typhimurium, as well as a moderate antifungal activity in resistant strains of Candida spp. They were inactive against anaerobes, which may indicate that the mechanism of action of these derivatives depends on the presence of oxygen. The capacity to inhibit the bacterial biofilm can be of particular interest in the treatment of nosocomial infections and in the coating of surfaces of prostheses. Finally, the potent antiviral activity observed converts these selenium derivatives into promising antiviral agents with potential medical applications.

Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors

Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in Staphylococcus aureus, methicillin resistant S. aureus (MRSA), Enterococcus faecalis, Escherichia coli, and Chlamydia trachomatis D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogen

Solution equilibrium, structural and cytotoxicity studies on Ru(η6-p-cymene) and copper complexes of pyrazolyl thiosemicarbazones

Solution chemical properties of two bidentate pyrazolyl thiosemicarbazones 2-((3-methyl-1-phenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Me-pyrTSC), 2-((1, 3-diphenyl-1H-pyrazol-4-yl)methylene)hydrazinecarbothioamide (Ph-pyrTSC), stability of their Cu(II) and Ru(η6-p-cymene) complexes were characterized in aqueous solution (with 30% DMSO) by the combined use of UV–visible spectrophotometry, 1H NMR spectroscopy and electrospray ionization mass spectrometry in addition to their solid phase isolation. The solid phase structures of Me-pyrTSC∙H2O, [Ru(η6-p-cymene)(Me-pyrTSC)Cl]Cl and [Cu(Ph-pyrTSCH−1)2] were determined by single crystal X-ray diffraction. High stability mononuclear Ru(η6-p-cymene) complexes with (N, S) coordination mode are formed in the acidic pH range, and increasing the pH the predominating dinuclear [(Ru(η6-p-cymene))2(L)2]2+ complex with μ2-bridging sulphur donor atoms is formed (where L− is the deprotonated thiosemicarbazone). [CuL]+ and [CuL2] complexes show much higher stability compared to that of complexes of the reference compound benzaldehyde thiosemicarbazone. [CuL2] complexes predominate at neutral pH. Me-pyrTSC and Ph-pyrTSC exhibited moderate cytotoxicity against human colonic adenocarcinoma cell lines (IC50 = 33–76 μM), while their complexation with Ru(η6-p-cymene) (IC50 = 11–24 μM) and especially Cu(II) (IC50 = 3–6 μM) resulted in higher cytotoxicity. Cu(II) complexes of the tested thiosemicarbazones were also cytotoxic in three breast cancer and in a hepatocellular carcinoma cell line. No reactive oxygen species production was detected and the relatively high catalase activity of SUM159 breast cancer cells was decreased upon addition of the ligands and the complexes. In the latter cell line the tested compounds interfered with the glutathione synthesis as they decreased the concentration of this cellular reductant

pH Modulation of Efflux Pump Activity of Multi-Drug Resistant Escherichia coli: Protection During Its Passage and Eventual Colonization of the Colon

BACKGROUND:Resistance Nodulation Division (RND) efflux pumps of Escherichia coli extrude antibiotics and toxic substances before they reach their intended targets. Whereas these pumps obtain their energy directly from the proton motive force (PMF), ATP-Binding Cassette (ABC) transporters, which can also extrude antibiotics, obtain energy from the hydrolysis of ATP. Because E. coli must pass through two pH distinct environments of the gastrointestinal system of the host, it must be able to extrude toxic agents at very acidic and at near neutral pH (bile salts in duodenum and colon for example). The herein described study examines the effect of pH on the extrusion of ethidium bromide (EB). METHODOLOGY/PRINCIPAL FINDINGS:E. coli AG100 and its tetracycline induced progeny AG100(TET) that over-expresses the acrAB efflux pump were evaluated for their ability to extrude EB at pH 5 and 8, by our recently developed semi-automated fluorometric method. At pH 5 the organism extrudes EB without the need for metabolic energy (glucose), whereas at pH 8 extrusion of EB is dependent upon metabolic energy. Phe-Arg beta-naphtylamide (PAbetaN), a commonly assumed inhibitor of RND efflux pumps has no effect on the extrusion of EB as others claim. However, it does cause accumulation of EB. Competition between EB and PAbetaN was demonstrated and suggested that PAbetaN was preferentially extruded. A K(m) representing competition between PAbetaN and EB has been calculated. CONCLUSIONS/SIGNIFICANCE:The results suggest that E. coli has two general efflux systems (not to be confused with a distinct efflux pump) that are activated at low and high pH, respectively, and that the one at high pH is probably a putative ABC transporter coded by msbA, which has significant homology to the ABC transporter coded by efrAB of Enterococcus faecalis, an organism that faces similar challenges as it makes its way through the toxic intestinal system of the host