In vitro anticancer activity of parent and nano-encapsulated samarium(iii) complex towards antimicrobial activity studies and FS-DNA/BSA binding affinity

Based on the potential anticancer properties of lanthanide complexes, the anticancer activity of the Sm(iii) complex containing a 2,2′-bipyridine ligand (bpy) and its interaction with FS-DNA (Fish-Salmon DNA) and BSA (Bovine Serum Albumin) were examined experimentally and by molecular docking in this paper. Absorption and fluorescence spectroscopic methods were used to define the thermodynamic parameters, binding constant (K_b), and the probable binding mechanism. It was concluded that the Sm complex interacts with FS-DNA through a minor groove with a K_b of 10⁵ M⁻¹. Also, the K_b for the BSA binding at 298 K was found to be 5.89 × 10⁵ M⁻¹, showing relatively a high tendency of the Sm complex to DNA and BSA. Besides, the Sm complex was docked to BSA and DNA by the autodock program. The results of the docking calculations were in good agreement with the experimental examinations. Additionally, the antifungal and antibacterial properties of this complex were investigated. The anticancer tests on the effect of the Sm complex, starch nano-encapsulation, and lipid nano-encapsulation in MCF-7 and A-549 cell lines were performed by the MTT method. It can be observed that the Sm complex and its nanocarriers presented a selective inhibitory effect on various cancer cell growths.

The biological properties of the Sm-complex, such as its interaction with FS-DNA and BSA, anticancer, and antimicrobial activities were studied.     

Synthesis,spectroscopic, thermal,antimicrobial and electrochemical characterization of some novel Ru(iii), Pt(iv) and Ir(iii) complexes of pipemidic acid

Three new solid complexes of pipemidic acid (Pip–H) with Ru³⁺, Pt⁴⁺ and Ir³⁺ were synthesized and characterized. Pipemidic acid acts as a uni-dentate chelator through the nitrogen atom of the –NH piperazyl ring. The spectroscopic data revealed that the general formulas of Pip–H complexes are [M(L)_n(Cl)_x]·yH₂O ((1) M = Ru³⁺, L: Pip–H, n = 3, x = 3, y = 6; (2) M = Pt⁴⁺, L: Pip–NH₄, n = 2, x = 4, y = 0 and (3) M = Ir³⁺, L: Pip–H, n = 3, x = 3, y = 6). The number of water molecules with their locations inside or outside the coordination sphere were assigned via thermal analyses (TG, DTG). The DTG curves refer to 2–3 thermal decomposition steps where the first decomposition step at a lower temperature corresponds to the loss of uncoordinated water molecules followed by the decomposition of Pip–H molecules at higher temperatures. Thermodynamic parameters (E*, ΔS*, ΔH* and ΔG*) were calculated from the TG curves using Coats–Redfern and Horowitz–Metzeger non-isothermal models. X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM) techniques were carefully used to assign properly the particle sizes of the prepared Pip–H complexes. The biological enhancement of Pip–H complexes rather than free chelate were assessed in vitro against four kinds of bacteria G(+) (Staphylococcus epidermidis and Staphylococcus aureus) and G(−) (Klebsiella and Escherichia coli) as well as against the human breast cancer (MCF-7) tumor cell line.

Three new solid complexes of pipemidic acid (Pip–H) with Ru³⁺, Pt⁴⁺ and Ir³⁺ were synthesized and characterized. Pipemidic acid acts as a uni-dentate chelator through the nitrogen atom of the –NH piperazyl ring.     

Synthesis,characterization, and photoelectric properties of iridium(iii) complexes containing an N hetero-dibenzofuran C^N ligand

In this study, three high-efficient green light iridium(iii) complexes were designed and synthesized, wherein 2-methyl-8-(2-pyridine) benzofuran [2,3-B] pyridine (MPBFP) is the main ligand and three β-diketone derivatives, namely 3,7-diethyl-4,6-nondiazone (detd), 2,2,6,6-tetramethyl-3,5-heptyldione (tmd) and acetylacetone (acac), are ancillary ligands. The thermal stabilities, electrochemical properties, and electroluminescence (EL) performance of these three complexes, namely (MPBFP)₂ Ir(detd), (MPBFP)₂Ir(tmd) and (MPBFP)₂Ir(acac), were investigated. The results show that the absorption peaks of the three complexes range from 260 to 340 nm, and the maximum emission wavelengths are 537 nm, 544 nm and 540 nm, respectively. The LUMO level is −2.18 eV, −2.20 eV, −2.21 eV, and the HOMO level is −5.30 eV, −5.25 eV, and −5.25 eV, respectively. The thermal decomposition temperatures of each of the three compounds are 359 °C, 389 °C and 410 °C respectively, with a weight loss of 5%. Green phosphorescent electroluminescent devices were prepared with the structure of ITO/HAT-CN/TAPC/TCTA/TCTA:X/Bepp2/LiF/Al, and the three complexes were dispersed in the organic light-emitting layer as the guest material X. The maximum external quantum efficiency of the devices is 17.2%, 16.7%, and 16.5%, respectively. The maximum brightness is 57 328 cd m⁻², 69 267 cd m⁻² and 69 267 cd m⁻², respectively. With respect to the EL properties, (MPBFP)₂Ir(detd) is the best performer among the three complexes. The different performances exhibited by these complexes were discussed from the view point of substituent effect on the β-diketone ligands.

Three high-efficient green light iridium complexes were designed and prepared. Thermal stabilities, electrochemical properties, electroluminescence performances and substituents effects are presented and discussed in this study.     

Parent and nano-encapsulated ytterbium(iii) complex toward binding with biological macromolecules,in vitro cytotoxicity,cleavage and antimicrobial activity studies

To determine the chemotherapeutic and pharmacokinetic aspects of an ytterbium complex containing 2,9-dimethyl-1,10-phenanthroline (Me₂Phen), in vitro binding studies were carried out with FS-DNA/BSA by employing multiple biophysical methods and a molecular modeling study. There are different techniques including absorption spectroscopy, fluorescence spectroscopy, circular dichroism studies, viscosity experiments (only in the case of DNA), and competitive experiments used to determine the interaction mode between DNA/BSA and the ytterbium-complex. The results showed that the Yb-complex exhibited a high propensity for the interaction of BSA and DNA via hydrophobic interactions and van der Waals forces. Further, a competitive examination and docking study showed that the interaction site of the ytterbium complex on BSA is site III. The results of docking calculations for DNA/BSA were in good agreement with experimental findings. The complex displays efficient DNA cleavage in the presence of hydrogen peroxide. Moreover, antimicrobial studies of different bacteria and fungi indicated its promising antibacterial activity. In vitro cytotoxicity studies of the Yb-complex, starch nano-encapsulated, and lipid nano-encapsulated were carried out in MCF-7 and A-549 cell lines, which revealed significantly good activity. The results of anticancer activity studies showed that the cytotoxic activity of the Yb-complex was increased when encapsulated with nanocarriers. Based on biological applications of the Yb-complex, it can be concluded that this complex and its nanocarriers can act as novel anticancer and antimicrobial candidates.

The biological applications of Yb-complexes including anticancer, antimicrobial and DNA cleavage ability, and their interaction with FS-DNA and BSA were examined.     

Water-soluble cyclometalated platinum(ii) and iridium(iii) complexes: synthesis,tuning of the photophysical properties,and in vitro and in vivo phosphorescence lifetime imaging

This paper presents synthesis and photophysical investigation of cyclometalated water-soluble Pt(ii) and Ir(iii) complexes containing auxiliary sulfonated diphosphine (bis(diphenylphosphino)benzene (dppb), P^P*) ligand. The complexes demonstrate considerable variations in excitation (extending up to 450 nm) and emission bands (with maxima ranging from ca. 450 to ca. 650 nm), as well as in the sensitivity of excited state lifetimes to molecular oxygen (from almost negligible to more than 4-fold increase in degassed solution). Moreover, all the complexes possess high two-photon absorption cross sections (400–500 GM for Pt complexes, and 600–700 GM for Ir complexes). Despite their negative net charge, all the complexes demonstrate good uptake by HeLa cells and low cytotoxicity within the concentration and time ranges suitable for two-photon phosphorescence lifetime (PLIM) microscopy. The most promising complex, [(ppy)₂Ir(sulfo-dppb)] (Ir1*), upon incubation in HeLa cells demonstrates two-fold lifetime variations under normal and nitrogen atmosphere, correspondingly. Moreover, its in vivo evaluation in athymic nude mice bearing HeLa tumors did not reveal acute toxicity upon both intravenous and topical injections. Finally, Ir1* demonstrated statistically significant difference in lifetimes between normal tissue (muscle) and tumor in macroscopic in vivo PLIM imaging.

Novel water-soluble iridium complexes with sulfonated diphosphine allow in vitro and in vivo lifetime hypoxia imaging.     

Cerium(iii) complexes with azolyl-substituted thiophenolate ligands: synthesis,structure and red luminescence

In order to obtain molecular Ce(iii) complexes which emit red light by f–d transitions the azolyl-substituted thiophenolates were used as the ligands. The thiophenolate Ce(iii) complexes were synthesized by the reaction of Ce[N(SiMe₃)₂]₃ with respective thiophenols 2-(2′-mercaptophenyl)benzimidazole (H(NSN)), 2-(2′-mercaptophenyl)benzoxazole (H(OSN)) and 2-(2′-mercaptophenyl)benzothiazole (H(SSN)) in DME media. The structures of the benzimidazolate (Ce(NSN)₃(DME)) and benzothiazolate (Ce(SSN)₃(DME)) derivatives were determined by X-ray analysis which revealed that the cerium ion in the molecules is coordinated by one DME and three anionic thiophenolate ligands. The lanthanum complex La(OSN)₃(DME) has been synthesized similarly and structurally characterized. It was found that the solids of Ce(SSN)₃(DME) and Ce(OSN)₃(DME) exhibit a broad band photoluminescence peaking at 620 nm which disappears upon solvatation. With an example of OSN derivatives it was proposed that this behaviour is caused by the blue shift of the f–d transition of Ce³⁺ ions.

Novel Ce(iii) complexes with azolyl-substituted thiolate ligands have been synthesized. Some of them exhibit red PL.     

One pot synthesis of two cobalt(iii) Schiff base complexes with chelating pyridyltetrazolate and exploration of their bio-relevant catalytic activities

Two new cobalt(iii) tetrazolato complexes [Co(L¹)(PTZ)(N₃)] (1) and [Co(L²)(PTZ)(N₃)] (2) {where H₂L¹ = 2((3-(methylamino)propylimino)methyl)-6-methoxyphenol, H₂L² = 2((3-(dimethylamino)propylimino)methyl)-6-ethoxyphenol and HPTZ = 5-(2-pyridyl)tetrazole}, have been synthesized via in situ 1,3-dipolar cycloaddition reaction of 2-cyanopyridine and sodium azide in the presence of cobalt(ii) nitrate hexahydrate and respective Schiff bases in the open atmosphere. The structures of both complexes have been confirmed by single crystal X-ray diffraction studies. Features of noncovalent interactions in the solid state of both complexes have been studied by means of DFT and MEP calculations and characterized using Bader''s theory of “atoms in molecules” (AIM). These complexes act as biomimetic catalysts promoting the aerobic oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to the corresponding o-benzoquinone at room temperature. The reaction follows Michaelis–Menten enzymatic reaction kinetics with turnover numbers of ∼0.030 s⁻¹ in an acetonitrile–methanol (2 : 1) mixture. Both complexes are also reactive towards aerobic oxidation of o-aminophenol in acetonitrile–methanol (2 : 1) with turnover numbers ∼0.095 s⁻¹.

Two cobalt(iii) tetrazolato complexes have been synthesized and characterized. Noncovalent interactions have been analysed by DFT and MEP calculations and characterized using Bader''s theory of AIM. Both complexes catalyze the aerial oxidation of 3,5-DTBC and OAPH.     

In vitro and in vivo antibacterial activities of a novel glycylcycline, the 9-t-butylglycylamido derivative of minocycline (GAR-936)

The 9-t-butylglycylamido derivative of minocycline (TBG-MINO) is a recently synthesized member of a novel group of antibiotics, the glycylcyclines. This new derivative, like the first glycylcyclines, the N,N-dimethylglycylamido derivative of minocycline and 6-demethyl-6-deoxytetracycline, possesses activity against bacterial isolates containing the two major determinants responsible for tetracycline resistance: ribosomal protection and active efflux. The in vitro activities of TBG-MINO and the comparative agents were evaluated against strains with characterized tetracycline resistance as well as a spectrum of recent clinical aerobic and anaerobic gram-positive and gram-negative bacteria. TBG-MINO, with an MIC range of 0.25 to 0.5 microgram/ml, showed good activity against strains expressing tet(M) (ribosomal protection), tet(A), tet(B), tet(C), tet(D), and tet(K) (efflux resistance determinants). TBG-MINO exhibited similar activity against methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and vancomycin-resistant enterococci (MICs at which 90% of strains are inhibited, < or = 0.5 microgram/ml). TBG-MINO exhibited activity against a wide diversity of gram-negative aerobic and anaerobic bacteria, most of which were less susceptible to tetracycline and minocycline. The in vivo protective effects of TBG-MINO were examined against acute lethal infections in mice caused by Escherichia coli, S. aureus, and Streptococcus pneumoniae isolates. TBG-MINO, administered intravenously, demonstrated efficacy against infections caused by S. aureus including MRSA strains and strains containing tet(K) or tet(M) resistance determinants (median effective doses [ED50s], 0.79 to 2.3 mg/kg of body weight). TBG-MINO demonstrated efficacy against infections caused by tetracycline-sensitive E. coli strains as well as E. coli strains containing either tet(M) or the efflux determinant tet(A), tet(B), or tet(C) (ED50s, 1.5 to 3.5 mg/kg). Overall, TBG-MINO shows antibacterial activity against a wide spectrum of gram-positive and gram-negative aerobic and anaerobic bacteria including strains resistant to other chemotherapeutic agents. The in vivo protective effects, especially against infections caused by resistant bacteria, corresponded with the in vitro activity of TBG-MINO.     

Spectro-electrochemical assessments of DNA/BSA interactions,cytotoxicity, radical scavenging and pharmacological implications of biosensitive and biologically active morpholine-based metal(ii) complexes: a combined experimental and computational investigation

Biosensitive and biologically active morpholine-based transition metal(ii) complexes (1–5) were constructed as [M^II(L) AcO]·nH₂O {where M = Cu (1) n = 1; Co (2), Mn (3), Ni (4), n = 4 and Zn (5) n = 2}, which were synthesized from 2-(-(2-morpholinoethylimino) methyl)-4-bromophenol ligand (HL) and structurally characterized by various analytical and spectroscopic techniques, which proposed a square planar and tetrahedral geometry around the central metal ion with lattice water molecules. The gel electrophoresis results revealed that complexes 1 and 5 had more potent DNA cleavage efficacy in the presence of an oxidizing agent (H₂O₂) as compared to the others. The observed DNA binding results for all the compounds as determined by spectro-electrochemical and hydrodynamic techniques were in the order 3.36 (1) > 3.06 (2) > 2.73 (4) > 2.61 (5) > 1.84 (3) > 1.00 (HL) × 10⁴ M⁻¹. The obtained bovine serum albumin (BSA) protein binding constant (K_b) results put forward the following order 2.38 (1) > 2.21 (2) > 2.18 (5) > 1.76 (4) > 1.40 (3) > 1.26 (HL) × 10⁴ M⁻¹. Also, the biothermodynamic parameters (, , ΔH° and ΔS°) and binding results divulged that all the complexes (1–5) could bind to DNA via intercalation in a spontaneous manner. Density functional theory calculations were employed to optimize the structure of ligand (HL) and its complexes (1–5) to gain insights into their electronic structures. Molecular docking analysis was carried out to identify the preferential binding modes of these complexes toward DNA and BSA protein. The theoretical observations of all cases were found to be very close to the experimental observations. Among the radical scavenging activity results for all the cases toward DPPH, hydroxyl radical, superoxide, nitric oxide and ferric reducing agents, complex (1) revealed a superior scavenging potency over the other compounds. In the screened antimicrobial reports against 10 different selected pathogenic species, although all the complexes (1–5) exhibited a greater significant inhibitory effect than the free ligand, complexes 4 and 5 achieved the best potency over standard drugs. The observed percentage of growth inhibition for all the compounds against the A549, HepG2, MCF-7 and NHDF cell lines suggested that complex 1 had enhanced growth-inhibitory potency over the other compounds and slightly affected normal cells as compared to the standard drug cisplatin, which may lead to its investigation as a promising anticancer agent in future research.

Morpholine-based metal(ii) complexes exhibited more significant biological activities than the free ligand. Among investigations towards DNA/BSA, the copper complex revealed excellent intercalating efficacy, which suggests it may have potential as a novel anticancer agent.     

Synthesis,crystal structures,and luminescent properties of Zn(ii), Cd(ii), Eu(iii) complexes and detection of Fe(iii) ions based on a diacylhydrazone Schiff base

Acylhydrazone Schiff bases are rich in N and O atoms to coordinate with metal ions to form multidentate complexes. In this study, a novel diacylhydrazone Schiff base (N′¹E,N′⁴E)-N′¹,N′⁴-bis(2-hydroxy-5-nitrobenzylidene)succinohydrazide (H₄L) was synthesized from the condensation of nitrosalicylaldehyde and succinic dihydrazide. The interactions of H₄L with common monovalent, divalent and trivalent metal ions were investigated by ultraviolet spectroscopy and fluorescence spectroscopy. The results showed that H₄L had no obvious effect on the monovalent metal ions (Li⁺, Na⁺, K⁺), but reacted with most divalent and trivalent metal ions, and showed single selectivity in the fluorescence recognition of Fe³⁺ ions. More importantly, three kinds of binuclear molecular structures, [Zn₂(H₂L)₂]·5DMF (Zn-L), [Cd₂(H₂L)₂]·DMF·H₂O (Cd-L) and [Eu₂(H₂L)₃]·6DMSO (Eu-L), have been studied to further illustrate the interaction mode of diacylhydrazone Schiff base and metal ions. In addition, the optical properties of these crystallized complexes have been studied in DMF solution.

Acylhydrazone Schiff bases are rich in N and O atoms to coordinate with metal ions to form multidentate complexes.     

Tetranuclear Cu(ii)-chiral complexes: synthesis,characterization and biological activity

Tetranuclear chiral Cu(ii)-Schiff-base complexes S-1 and R-1, were synthesised using enantiomerically pure (S)-(H₂vanPheol) and (R)-(H₂vanPheol) ligands respectively in the ratio of 1 : 1 of Cu(NO₃)₂ to (S/R)-(H₂vanPheol) in MeOH at room temperature. A pair of polynuclear chiral Cu(ii)-cluster complexes were characterized using single-crystal X-ray diffraction, elemental analysis, infrared and CD spectroscopy. The results revealed the importance of these chiral ligands encouraging the arrangement of copper metal in non-centrosymmetric polar packing. The potential of the novel [Cu₄(S/R-vanPheol)₂(S/R-HvanPheol)₂(CH₃OH)₂](NO₃)₂ complexes as biologically active compounds was assessed in particular regarding their anti-proliferative and anti-microbial properties.

A pair of tetranuclear chiral Cu(ii)-Schiff-base complexes were synthesized using enantiomerically pure (S)-H₂L and (R)-H₂L ligands. These were characterised using single-crystal X-ray diffraction and CD spectroscopy and their biological activity tested.     

Fullerene-modified magnetic silver phosphate (Ag3PO4/Fe3O4/C60) nanocomposites: hydrothermal synthesis,characterization and study of photocatalytic,catalytic and antibacterial activities

In this work, fullerene-modified magnetic silver phosphate (Ag₃PO₄/Fe₃O₄/C₆₀) nanocomposites with efficient visible light photocatalytic and catalytic activity were fabricated by a simple hydrothermal approach. The composition and structure of the obtained new magnetically recyclable ternary nanocomposites were completely characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, Brunauer–Emmett–Teller (BET) specific surface area analysis, vibrating sample magnetometery (VSM), diffuse reflectance spectroscopy (DRS), field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray (EDX) spectroscopy and transmission electron microscopy (TEM). This novel magnetically recyclable heterogeneous fullerene-modified catalyst was tested for the H₂O₂-assisted photocatalytic degradation of MB dye under visible light. The results show that about 95% of the MB (25 mg L⁻¹, 50 ml) was degraded by the Ag₃PO₄/Fe₃O₄/C₆₀ nanocomposite within 5 h under visible light irradiation. The catalytic performance of the Ag₃PO₄/Fe₃O₄/C₆₀ nanocomposite was then examined for 4-nitrophenol (4-NP) reduction using NaBH₄. This new nanocomposite showed that 4-NP was reduced to 4-aminophenol (4-AP) in 98% yield with an aqueous solution of NaBH₄. In both photocatalytic and catalytic reactions, the Ag₃PO₄/Fe₃O₄/C₆₀ nanocomposite exhibited higher catalytic activity than pure Ag₃PO₄. Moreover, the Ag₃PO₄/Fe₃O₄/C₆₀ nanocomposite could be magnetically separated from the reaction mixture and reused without any change in structure. The antibacterial activity of the nanocomposites was also investigated and they showed good antibacterial activity against a few human pathogenic bacteria.

Fullerene-modified magnetic silver phosphate (Ag₃PO₄/Fe₃O₄/C₆₀) nanocomposites prepared by a hydrothermal route were used as photocatalysts/catalysts for the efficient degradation and reduction of MB dye and 4-nitrophenol, respectively.     

Copper(ii) complexes with terpene derivatives of ethylenediamine: synthesis,and antibacterial,antifungal and antioxidant activity

The synthesis of new chiral copper(ii) complexes with terpene derivatives of ethylenediamine and the results of studying their antibacterial, antifungal and antioxidant activity in vitro are discussed. All studied copper complexes (1–4) showed significantly higher antifungal activity against the strains of C. albicans, S. salmonicolor and P. notatum compared to the activity of the clinical antifungal drug amphotericin. High antibacterial activity of copper complexes with terpene derivatives of ethylenediamine was revealed against the S. aureus (MRSA) strain, which is resistant to the reference antibiotic ciprofloxacin. Using various test systems, a comparative assessment of the antioxidant activity (AOA) of the synthesized copper complexes and the ligands was carried out. The salen-type complex 4, which has the highest AOA in the model of initiated oxidation of a substrate containing animal lipids, was superior to other copper complexes in the ability to protect erythrocytes under conditions of H₂O₂-induced hemolysis.

The synthesis of new chiral copper(ii) complexes with terpene derivatives of ethylenediamine and the results of studying their antibacterial, antifungal and antioxidant activity in vitro are discussed.     

Anticancer steroid sulfatase inhibitors: synthesis of a potent fluorinated second-generation agent, in vitro and in vivo activities, molecular modeling, and protein crystallography

An improved steroid sulfatase inhibitor was prepared by replacing the N-propyl group of the second-generation steroid-like inhibitor (2) with a N-3,3,3-trifluoropropyl group to give (10). This compound is 5-fold more potent in vitro, completely inhibits rat liver steroid sulfatase activity after a single oral dose of 0.5 mg/kg, and exhibits a significantly longer duration of inhibition over (2). These biological properties are attributed to the increased lipophilicity and metabolic stability of (10) rendered by its trifluoropropyl group and also the potential H-bonding between its fluorine atom(s) and Arg(98) in the active site of human steroid sulfatase. Like other sulfamates, (10) is expected to be sequestered, and transported by, erythrocytes in vivo because it inhibits human carbonic anhydrase II (hCAII) potently (IC(50), 3 nmol/L). A congener (4), which possesses a N-(pyridin-3-ylmethyl) substituent, is even more active (IC(50), 0.1 nmol/L). To rationalize this, the hCAII-(4) adduct, obtained by cocrystallization, reveals not only the sulfamate group and the backbone of (4) interacting with the catalytic site and the associated hydrophobic pocket, respectively, but also the potential H-bonding between the N-(pyridin-3-ylmethyl) group and Nepsilon(2) of Gln(136). Like (2), both (10) and its phenolic precursor (9) are non-estrogenic using a uterine weight gain assay. In summary, a highly potent, long-acting, and nonestrogenic steroid sulfatase inhibitor was designed with hCAII inhibitory properties that should positively influence in vivo behavior. Compound (10) and other related inhibitors of this structural class further expand the armory of steroid sulfatase inhibitors against hormone-dependent breast cancer.     

Design,synthesis and characterization of novel chromone based-copper(ii) antitumor agents with N,N-donor ligands: comparative DNA/RNA binding profile and cytotoxicity

A series of new chromone based-Cu(ii) complexes 1–3 derived from bioactive pharmacophore, 3-formylchromone and N,N-donor ligands viz., 1,10-phenanthroline, 2,2′-bipyridine and 1R,2R-DACH were synthesized as potential antitumor agents and thoroughly characterized by UV-vis, FT-IR, EPR, ESI-MS and elemental analysis. Single X-crystal diffraction studies of complex 2 revealed triclinic P$\bar{1}$ space group with square pyramidal geometry around the Cu(ii) center. Comparative in vitro binding studies with ct-DNA and tRNA were carried out using absorption and emission titration experiments which revealed intercalative mode of binding with higher binding propensity of complexes 1–3 towards tRNA as compared to ct-DNA. Additionally, complex 1 exhibited high binding affinity among all the three complexes due to the involvement of phen co-ligands via π-stacking interactions in between nucleic acid base pairs. Furthermore, Hirshfeld surface analysis was carried out for complex 2 to investigate various intra and intermolecular non-covalent interactions (H-bonding, C–H⋯π etc.) accountable for stabilization of crystal lattice. The cleavage activity of complex 1 was performed by gel electrophoretic assay with pBR322 DNA and tRNA which revealed efficient DNA/tRNA cleaving ability of complex, suggesting tRNA cleavage both concentration and time dependent. Furthermore, in vitro cytotoxic activity of complexes 1–3 on a selected panel of human cancer cell lines was performed which revealed that all three complexes exhibited remarkably good cytotoxic activity with GI₅₀ value < 10 μg mL⁻¹ (<20 μM).

New chromone-based Cu(ii) tRNA targeted complexes 1–3 as potential anticancer agents have been synthesized and thoroughly characterized.     

Crystal structure,spectroscopic measurement,optical properties,thermal studies and biological activities of a new hybrid material containing iodide anions of bismuth(iii)

As part of our interest in halogenobismuthate(iii) organic–inorganic hybrid materials, a novel compound named bis(4,4′-diammoniumdiphenylsulfone) hexadecaiodotetrabismuthate(III) tetrahydrate with the chemical formula (C₁₂H₁₄N₂O₂S)₂[Bi₄I₁₆]·4H₂O, abbreviated as (H₂DDS)[Bi₄I₁₆], has been prepared by a slow evaporation method at room temperature. This compound was characterized by single crystal X-ray diffraction (SCXRD), spectroscopic measurements, thermal study and antimicrobial activity. The examination of the molecular arrangement shows that the crystal packing can be described as made of layers of organic [C₁₂H₁₄N₂O₂S]²⁺ entities and H₂O molecules, between which tetranuclear [Bi₄I₁₆]⁴⁻ units, isolated from each other, are inserted. The cohesion among the different molecules is assured by N–H⋯I, N–H⋯O and O–H⋯I hydrogen bonding interactions, forming a three-dimensional network. Room temperature IR, Raman spectroscopy of the title compound were recorded and analyzed. The optical properties were also investigated by both UV-vis and photoluminescence spectroscopy. Moreover, the synthesized compound was also screened for in vitro antimicrobial (Gram-positive and Gram-negative) and antioxidant activities (scavenging effect on DPPH free radicals, reducing power and total antioxidant capacity).

A novel halogenobismuthate(iii) organic–inorganic hybrid material named bis(4,4′-diammoniumdiphenylsulfone) hexadecaiodotetrabismuthate(iii) tetrahydrate, (C₁₂H₁₄N₂O₂S)₂[Bi₄I₁₆]·4H₂O, has been prepared by slow evaporation at room temperature.     

Synthesis,crystal structures,DNA interactions,and antitumor activity of two new dinuclear copper(ii) complexes with thiazole ligand

Two new dinuclear copper(ii) complexes, [Cu(ambt)₂(cnba)₄] (1) and [Cu(ambt)₂(clba)₄] (2) were synthesized with 2-amino-6-methoxybenzothiazole (ambt) as the main ligand. The structures of the two complexes were characterized by single-crystal XRD. The binding between CT-DNA (calf thymus DNA) and the complexes was evaluated by viscometry, electronic absorption, and fluorescence spectroscopy, and the binding constants were calculated using the Stern–Volmer equation. The complexes were intercalatively bound to CT-DNA, and [Cu(ambt)₂(clba)₄] having a greater binding constant than [Cu(ambt)₂(cnba)₄]. The two complexes had better antitumor properties against HepG2 (human hepatocellular carcinoma), A549 (human lung carcinoma), and HeLa (human cervical carcinoma) tumor cell lines than their respective ligands and cisplatin. Furthermore, [Cu(ambt)₂(clba)₄] had a stronger inhibitory ability on the three types of tumor cells than [Cu(ambt)₂(cnba)₄], which is congruent with the binding power of the complexes with DNA. Flow cytometry revealed that [Cu(ambt)₂(cnba)₄] and [Cu(ambt)₂(clba)₄] could trigger apoptosis or necrosis, arrest the HepG2 cell cycles, and cause G0/G1-phase cells to accumulate.

Two new dinuclear copper(ii) complexes, [Cu(ambt)₂(cnba)₄] (a) and [Cu(ambt)₂(clba)₄] (b) were synthesized with 2-amino-6-methoxybenzothiazole (ambt) as the main ligand.     

In vitro and in vivo antimicrobial activities of T-3811ME, a novel des-F(6)-quinolone

The in vitro and in vivo activities of T-3811ME, a novel des-F(6)-quinolone, were evaluated in comparison with those of some fluoroquinolones, including a newly developed one, trovafloxacin. T-3811, a free base of T-3811ME, showed a wide range of antimicrobial spectra, including activities against Chlamydia trachomatis, Mycoplasma pneumoniae, and Mycobacterium tuberculosis. In particular, T-3811 exhibited potent activity against various gram-positive cocci, with MICs at which 90% of the isolates are inhibited (MIC90s) of 0.025 to 6.25 microgram/ml. T-3811 was the most active agent against methicillin-resistant Staphylococcus aureus and streptococci, including penicillin-resistant Streptococcus pneumoniae (PRSP). T-3811 also showed potent activity against quinolone-resistant gram-positive cocci with GyrA and ParC (GrlA) mutations. The activity of T-3811 against members of the family Enterobacteriaceae and nonfermentative gram-negative rods was comparable to that of trovafloxacin. In common with other fluoroquinolones, T-3811 was highly active against Haemophilus influenzae, Moraxella catarrhalis, and Legionella sp., with MIC90s of 0.0125 to 0.1 microgram/ml. T-3811 showed a potent activity against anaerobic bacteria, such as Bacteroides fragilis and Clostridium difficile. T-3811 was the most active agent against C. trachomatis (MIC, 0.008 microgram/ml) and M. pneumoniae (MIC90, 0.0313 microgram/ml). The activity of T-3811 against M. tuberculosis (MIC90, 0.0625 microgram/ml) was potent and superior to that of trovafloxacin. In experimental systemic infection with a GrlA mutant of S. aureus and experimental pneumonia with PRSP in mice, T-3811ME showed excellent therapeutic efficacy in oral and subcutaneous administrations.     

Ru(ii)–N-heterocyclic carbene complexes: synthesis,characterization, transfer hydrogenation reactions and biological determination

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions. All new compounds were characterized by spectroscopic and analytical methods. These ruthenium(ii)–NHC complexes were found to be efficient precatalysts for the transfer hydrogenation of ketones by using 2-propanol as the hydrogen source in the presence of KOH as a co-catalyst. The antibacterial activity of ruthenium N-heterocyclic carbene complexes 3a–f was measured by disc diffusion method against Gram positive and Gram-negative bacteria. Compounds 3d exhibited potential antibacterial activity against five bacterial species among the six used as indicator cells. The product 3e inhibits the growth of all the six tested microorganisms. Moreover, the antioxidant activity determination of these complexes 3a–f, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) as reagent, showed that compounds 3b and 3d possess DPPH and ABTS antiradical activities. From a concentration of 1 mg ml⁻¹, these two complexes presented a similar scavenging activity to that of the two used controls gallic acid (GA) and butylated hydroxytoluene (BHT). From a concentration of 10 mg ml⁻¹, the percentage inhibition of complexes 3b and 3d was respectively 70% and 90%. In addition, these two Ru–NHC complexes exhibited antifungal activity against Candida albicans. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a, 3b, 3d and 3e exhibited good activity at 100 μg ml⁻¹ and product 3d is the most active. In a cytotoxicity study the complexes 3 were evaluated against two human cancer cell lines MDA-MB-231 and MCF-7. Both 3d and 3e complexes were found to be active against the tested cell lines showing comparable activity with examples in the literature.

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions.