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A perceived drawback of ruthenium(II) polypyridyl photosensitizers for phototherapeutic applications is their inadequate absorption in the visible region. Ru(II) dyads attached to light‐harvesting organic chromophores are studied to address this issue. Biotin‐appended compounds having one chromophore, namely BODIPY (boron‐dipyrromethene) (1) and Ru(II)‐(tpy)2 (2), or a dyad system containing BODIPY linked to Ru(II)‐(tpy)2 via a diphenylacetylene linker (3) were prepared and studied as photodetection agent and photosensitizes for Photodynamic Therapy (PDT) applications. The bichromophoric 3 with a strong absorption profile (ϵ≈71000 M−1 cm−1 at λmax=503 nm) and high singlet oxygen quantum yield (ΦΔ=0.63 in DMSO) was studied for PDT activity. This complex produced a superoxide anion radical via type‐I and singlet oxygen via type‐II photosensitization processes on light exposure, as evidenced from DNA photo‐cleavage experiments and in vitro DCFDA assay using reactive oxygen species scavengers/quenchers. Dyad 3 displayed an apoptotic photo‐cytotoxic effect against HeLa and H1299 cancer cells with a photocytotoxicity index (PI) value of >625 in HeLa cells with a PDT efficacy much superior to those of its monochromophoric analogs 1 and 2. The intrinsic emission of complex 3, utilized for cellular imaging, showed selectivity towards lysosomes. Finally, the remarkable potential of complex 3 was evidenced using a clinically relevant 3D multicellular tumor spheroid model. [ABSTRACT FROM AUTHOR]

As a kind of multifunctional materials with high porosity, tunable pore structure and easy functionalization, coordination complexes have been widely used in various fields. Here, three complexes were prepared by self‐assembly with Co(II) ions using tetrazolylacetic acids as ligands, 2,2′,2′′‐(benzene‐1,3,5‐triyltris(2H‐tetrazole‐5,2‐diyl)) triacetic acid (H3tzpha), 2‐(5‐(pyrazin‐2‐yl)‐2H‐tetrazol‐2‐yl) propanoic acid (Hpztzma) and 2‐(5‐(pyridin‐2‐yl)‐2H‐tetrazol‐2‐yl) acetic acid (Hpytza), and were characterized by X‐ray crystallography. These complexes can also self‐assemble into nanoparticles (NPs) in aqueous solution by nanocoprecipitation. In vitro CCK‐8 assay on three kind of human cancer cells (HeLa, HepG2 and Huh7) cells showed these Co(II) complexes have the best cytotoxicity against HeLa cells. And complex 1 had a half maximal inhibitory concentration (IC50 value) of 14.8 μg mL−1, which was superior to 16.5 μg mL−1 and 15.2 μg mL−1 of complex 2 and 3. In addition, the effect of different ligands on cancer cell ablation was explored. The results showed the three NPs can effectively inhibit the proliferation of cancer cells in vitro and provided a strategy on designing highly efficient anticancer materials based on coordination complexes. [ABSTRACT FROM AUTHOR]

Reductive aminations of ferrocenecarboxaldehyde, ansa‐ferrocenecarboxaldehyde, and 1,1′‐ferrocene‐dicarboxaldehyde with allylamine, N‐allylmethylamine, or N‐allylaniline were investigated. In the case of the dialdehyde only one formyl group effectively reacted with N‐allylmethylamine or N‐allylaniline, thus providing a simple route to aminomethyl aldehydes and aminomethyl alcohol. 2‐Aza‐ansa[3] ferrocene was also obtained by reacting the dialdehyde with one equivalent of allylamine and subsequent deprotection of the nitrogen atom. The isolated N‐allyl ferrocene derivatives were completely characterized by spectroscopic techniques, whereas crystal structures of four representative compounds were determined using single‐crystal X‐ray diffraction. MTT assays showed that these simple N‐allyl ferrocene derivatives display anticancer activity (MCF‐7, A‐549 and PC‐3 cell lines) in the micromolar range. [ABSTRACT FROM AUTHOR]

The β‐diketone scaffold is a commonly used synthetic intermediate, and is a functional group found in natural products such as curcuminoids. This core structure can also act as a chelating ligand for a variety of metals. In order to assess the potential of this scaffold for medicinal inorganic chemistry, seven different κ2‐O,O'‐chelating ligands were used to construct Ru(II) complexes with polypyridyl co‐ligands, and their biological activity was evaluated. The complexes demonstrated promising structure‐dependent cytotoxicity. Three complexes maintained high activity in a tumor spheroid model, and all complexes demonstrated low in vivo toxicity in a zebrafish model. From this series, the best compound exhibited a ∼30‐fold window between cytotoxicity in a 3‐D tumor spheroid model and potential in vivo toxicity. These results suggest that κ2‐O,O'‐ligands can be incorporated into Ru(II)‐polypyridyl complexes to create favorable candidates for future drug development. [ABSTRACT FROM AUTHOR]

Iron(III) complexes of curcumin (Hcur) having a tridentate NNNdonor dipicolylamine-based ligand L¹ and its biotinylated analogue L², namely, [Fe(L¹)(cur)Cl] (1) and [Fe(L²)(cur)Cl] (2), were prepared, characterized and their photo-induced cytotoxicity studied. The complexes exhibited curcumin-based absorption band near 430 nm and emission maxima at 520 nm. Complex 2 with a biotin moiety showed enhanced cellular uptake and higher cytotoxicity compared to its non-biotin analogue 1. The visible light induced cytotoxicity was studied in HeLa, MCF-7 and HepG2 cell lines. Complex 2 displayed photodynamic effect (400-700 nm, 10 Jcm-2) giving an IC50 value of ~4 μM in HeLa and MCF-7 cells, while being significantly nontoxic in the dark (IC50>100 μM). A 5-fold increase in cytotoxicity was observed in HepG2 cells (IC50~0.7 μM) for the biotinappended complex 2. In vitro generation of reactive oxygen species (ROS) was observed from dichlorofluorescein diacetate (DCFDA) assay. The mode of cell death was apoptotic. Formation of hydroxyl radicals as the ROS was evidenced from the plasmid pUC19 DNA photo-cleavage studies. The complexes demonstrated the ability to act as targeted PDT (photodynamic therapy) drugs. [ABSTRACT FROM AUTHOR]

Exploring the potential of bis(thiosemicarbazones) (BTSC), a new family of BTSC ligands derived from GTSM (glyoxal-bis(N4- methylthiosemicarbazonato) and respective CuIIBTSC complexes were synthesized. These complexes, having pendant nitrogen heterocycles, exhibited increased water-solubility, lower lipophilicity at physiological pH and more negative Cu(II)/Cu(I) redox potential, when compared with the parental complex. The cytotoxic evaluation performed in a panel of cancer cells lines showed an important effect of the metal complexation, and furthermore correlated well with the cellular uptake of the compounds, which was determined using their 64Cu congeners. The radiolabelling of the complexes also allowed more detailed uptake studies, with the results suggesting an active transport or facilitated diffusion mechanism for the cellular uptake of 64CuGTSMpip and 64CuGTSMmor, with pendant piperidine and morpholine rings, respectively. Additionally, a comparative study with the corresponding Cu(II) complexes derived from ATSM (diacetyl-bis(NU4-methylthiosemicarbazonato) that we have previously described, demonstrated a clear difference in their lysosomotropic properties in particular for the piperidine derivatives. From this study, CuGTSMpip emerged as the most promising compound to be further evaluated as an anticancer metallodrug. [ABSTRACT FROM AUTHOR]

Porphyrins and N‐heterocyclic carbenes (NHCs) are both relevant ligands in the fields of coordination and organometallic chemistry. Despite evident structural differences, porphyrins and NHCs have a lot in common such as their ability to form strong metal‐ligand bonds and their use in catalysis, materials science and biomedicine. During the last decade, several molecular systems combining porphyrins and NHC ligands were reported in the literature. The present review gathers relevant examples where NHC ligands are either axially bonded to metalloporphyrins or covalently attached to the porphyrin cores. Structural diversity, electronic interplay between porphyrins and NHCs and some relevant applications in catalysis and biomedicine are notably described. Finally, molecular systems combining NHCs with other original porphyrinoids such as N‐confused porphyrins, subporphyrins and norcorroles are also presented. [ABSTRACT FROM AUTHOR]

With about 4 % abundance in the genome 5‐methylcytosine (5mC) is one of the most important epigenetic modifications. Change in DNA hypermethylation levels has even been linked to resistances to cisplatin treatment of cancer cells. This work aimed at the synthesis and full characterization of 5mC‐cisplatin adducts as well as for the examination of possible side‐reactions and transformations. We report the first X‐ray crystal structure of a cis‐[PtCl(5mC)(NH3)2]Cl complex and the formation of [PtCl(5mC)(NH3)2]+ and [PtCl(5mC)2(NH3)]+ with HR‐ESI mass spectrometry. Further, we explore complex formation and dynamics using 1H, 195Pt, and DOSY NMR spectroscopy. UV/Vis absorption and EPR spectroscopy also confirmed the formation of trace amounts of paramagnetic Pt‐blue species. In the process, a hemiprotonated 5mC dimer, 5mC‐5mCH+, reminiscent of the "i‐motif" in DNA tetramers, was structurally characterized. [ABSTRACT FROM AUTHOR]

Great attention has been bestowed upon iridium(III) complexes as anticancer agents in recent years, and a variety of them, in particular, are luminescent. The phosphorescence of these compounds facilitates the visualization and monitoring of their subcellular localization and interactions with other molecules or structures during anticancer therapy, which might help demonstrate the inner pathways and molecular mechanisms of the complexes. In this review, we focus on the development of phosphorescent iridium(III) complexes for anticancer applications in recent five years and intend to highlight some newly reported Ir(III) complexes that are targeting specific organelles, inducing different cell death modes, or photoactivated agents in phototherapies including photodynamic therapy and photoredox catalysis. [ABSTRACT FROM AUTHOR]

Platinum pincer‐based complexes [(O^N^O)Pt(L)] (L = DMSO, pyridine, triphenylphosphine or 1,3‐dimethylbenzimidazol‐2‐ylidene) carrying an (N^N) coordination site were used as starting materials to synthesize a series of seven cationic heterobimetallic Pt(II)/Ru(II), Pt(II)/Ir(III), and Pt(II)/Cu(I) presenting a [(p‐cymene)RuCl]+, a [(Cp*)IrCl]+ (Cp* = η5‐pentamethylcyclopentadienyl), and a [(NHCiPr)Cu]+ {NHCiPr = 1,3‐bis(2,6‐diisopropylphenyl)imidazole‐2‐ylidene} moiety, respectively. The X‐ray structure of one of the bimetallic Pt(II)/Ir(III) complexes showed a distortion of the organic platform to accommodate the coordination geometry of both metal centers, as already observed for previous Pt(II)/Re(I) complexes. The antiproliferative activity of the complexes was first screened on the triple negative breast cancer cell line MDA‐MB‐231. Then the IC50 of the most active candidates was determined on a wider panel of human cancer cells (MDA‐MB‐231, MCF‐7 and A2780) as well as on a non‐tumorigenic cell line (MCF‐10A). The most toxic compound, namely the Pt(II)/Cu(I) heterobimetallic complex 4c, showed antiproliferative activity down to the nanomolar level. [ABSTRACT FROM AUTHOR]

The therapy of cancer remains a major challenge for modern medicine. Complementary to classical treatments, the use of photodynamic therapy (PDT) has received increasing attention over the last decades. Among the classes of PDT photosensitizers (PSs) investigated, RuII polypyridine complexes are currently considered as a valuable option. To improve the water solubility of these lipophilic compounds and generate a drug delivery system, these complexes can be encapsulated with polymers. Herein, the physical encapsulation of the photoactive [Ru((E,E')‐4,4'‐bis[p‐methoxystyryl]‐2,2'‐bipyridine)3][PF6]2 complex with the polymer Pluronic F‐127/Poloxamer‐407 is presented. The resulting spherical particles were found to have a toxic effect in the micromolar range in human cervical carcinoma cells upon light irradiation (500 nm). [ABSTRACT FROM AUTHOR]

We report the synthesis, characterization and cytotoxicity of six cyclometalated rhodium(III) complexes [CpXRh(C^N)Z]0/+, in which CpX = Cp*, Cpph, or Cpbiph, C^N = benzo[h]quinoline, and Z = chloride or pyridine. Three X‐ray crystal structures showing the expected "piano‐stool" configurations have been determined. The chlorido complexes hydrolyzed faster in aqueous solution, and reacted preferentially with 9‐ethyl guanine or glutathione compared to their pyridine analogues. The 1‐biphenyl‐2,3,4,5‐tetramethylcyclopentadienyl complex [CpbiphRh(benzo‐[h]quinoline)Cl] (3a) was the most efficient catalyst in coenzyme reduced nicotinamide adenine dinucleotide (NADH) oxidation to NAD+ and induced an elevated level of reactive oxygen species (ROS) in A549 human lung cancer cells. The pyridine complex [CpbiphRh(benzo[h]quinoline)py]+ (3b) was the most potent against A549 lung and A2780 ovarian cancer cell lines, being 5‐fold more active than cisplatin towards A549 cells, and acted as a ROS scavenger. This work highlights a ligand‐controlled strategy to modulate the reactivity and cytotoxicity of cyclometalated rhodium anticancer complexes. [ABSTRACT FROM AUTHOR]

With the aim to explore the effects of different organometallic ligands on the reactivity and biological properties of a series of twelve heteroleptic AuI complexes, of general formula [Au(NHC)(alkynyl)] (NHC = benzimidazolylidene or 1,3‐dihydroimidazolylidene) were synthesized and characterized by 1H and 13C NMR and elemental analysis, and in some cases also by X‐ray diffraction. The compounds were all stable in H2O/DMSO as established by NMR spectroscopy, while they could react with model thiols (EtSH) in the presence of water to undergo ligand‐substitution reactions. 1H NMR experiments showed that dissociation of the more labile alkynyl ligand was possible for all compounds, while in the case of the benzimidazolylidene series also dissociation of the NHC ligand could be observed. DFT calculations suggest that, depending on the steric hindrance exerted by both the NHC wingtip groups and the alkynyl substituents, the reaction can proceed either via a π‐stabilized intermediate or with the alkynyl ligand remaining purely σ‐coordinated to the AuI center until completely dissociated. The most stable compounds in PBS buffer (pH 7.4), as assessed by UV‐Visible spectrophotometry, were further investigated for their ability to stabilize G4 DNA by FRET DNA melting assay, showing only moderate activity. Moreover, two derivatives were tested in vitro for their anticancer activities in three different human cancer cell lines and showed cytotoxicity in the low micromolar range. [ABSTRACT FROM AUTHOR]

Five‐coordinate platinum(II) complexes represent a minority compared to the well‐known class of square‐planar species. However, since the first appearances in the literature, their general properties have attracted much interest. In particular, their potential to act as anticancer agents has been considered, and several studies have demonstrated their effectiveness as pro‐drugs. The review traces the progress of these investigations over time and the subsequent refinements in the structures. It also reports their synthesis, general properties, cytotoxic activity and ability to interact with biological macromolecules. [ABSTRACT FROM AUTHOR]

The discovery of cisplatin is an important milestone in the history of successful anticancer drugs. This is also a notable example of the translational scientific achievement that remains a driving force in multidisciplinary research. The clinical success of cisplatin has led chemists to vary the ligands around the platinum metal to improve cisplatin's effectiveness while reducing its side effects. While there have been more failures than successes, key developments in the elucidation of mechanisms of the tumor‐resistance properties have been accomplished. N‐Heterocyclic carbene as ligand for organometallic chemistry is a relatively young area that offers new opportunities in many fields including bio‐inorganic chemistry. These ligands fit the prerequisites for metal drug development and recent achievements have demonstrated the great potential of these compounds. The properties of these metal NHC complexes also allow for easy post‐functionalization, thus enabling molecular diversity for efficient drug design. Overall, N‐heterocyclic carbene ligands reveal new opportunities for Pt drug development. [ABSTRACT FROM AUTHOR]

Complementary to classical treatment methods used against cancer, photodynamic therapy (PDT) has received increasing attention over the last years. PDT relies on the generation of reactive oxygen species (ROS) upon light irradiation to trigger cell death. As the wavelength employed during such treatments directly influences the light penetration depth and therefore the possibility to treat deep seated tumors or large tumors, research efforts have been made towards the development of photosensitizers (PSs) with an absorption in the phototherapeutic window (600–900 nm). To tackle this drawback, we report herein the preparation and characterization of new RuII‐containing PDT PSs, that are based on a [Ru(bipy)3]2+ core (1; bipy: 2,2′‐bipyridine) and that are extended with methyl groups (2) or vinyl dimethylamino groups (3). As anticipated with our design, we found a red‐shift of 65 nm of the maximum absorption of complex 3 in comparison to complex 1. In addition, we report on the in‐depth photophysical properties as well as (photo‐)cytotoxicity against cervical cancerous HeLa cells of the investigated compounds. [ABSTRACT FROM AUTHOR]

The oxaliplatin derivative (SP‐4‐3)‐oxalato[(1R,2R,4R/1S,2S,4S)‐(4‐trifluoromethyl‐cyclohexane‐1,2‐diamine)]platinum(II) hosting a trifluoromethyl group at position 4 of the cyclohexane ring is presented. The ligand was synthesized as an 1R,2R,4R/1S,2S,4S racemic mixture starting from 4‐trifluoromethyl‐cyclohexanol over five steps and coordinated to platinum to yield first the dichlorido and subsequently the oxalato complex. This novel compound and its analogue featuring a (13C2)oxalate ligand were characterized by multinuclear (1H, 13C, 15N, 19F, 195Pt) one‐ and two‐dimensional NMR spectroscopy. Ligand exchange and adduct formation reactions with DMSO, NaCl, CaCl2, l‐methionine, and 5′‐GMP were investigated via time‐dependent measurements by 19F and 13C NMR spectroscopy. The cytotoxicity of the title complex was investigated in three human cancer cell lines; the IC50 values were found in the low micromolar range, attesting moderate to high antiproliferative activity, depending on the cell line. A racemic mixture of an analogue of the clinically established anticancer drug oxaliplatin featuring a CF3 group at position 4 of the cyclohexane ring was synthesized and fully characterized. Its binding to DMSO, chloride, 5′‐GMP, and l‐methionine was investigated by 19F and 13C NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Representative polyoxometalates with proven bio‐active properties, namely {Sb9W21}, {P2W18} and {Mo7O24}, were encapsulated into chitosan and carboxymethyl chitosan (CMC) to afford nanoscale composites. The pristine POMs were characterized with a wide range of analytical techniques, including powder X‐ray diffraction as well as FT‐IR and 31P NMR spectroscopy. Size and morphology of their nanocomposites were determined within the 100–200 nm size range by dynamic light scattering (DLS) methods in combination with scanning and transmission electron microscopy. Their stability was monitored by UV/Vis and DLS measurements over several days. The cytotoxicity of pristine and encapsulated POMs was investigated on HeLa and MRC‐5 cell lines, representing cancer and normal cell lines, respectively. Our results suggest that CMC encapsulation enhances the specificity towards cancer cells, especially in treatment approaches where a lower drug dose would be required. The anticancer activity of POMs emerged as a dynamic property that depends on manifold parameters, such as the POM structure, the polymeric drug carrier type, and the investigated cell line. Representative bio‐active polyoxometalates were encapsulated in chitosan and carboxymethyl chitosan forming nanoparticles of 100–200 nm. Selectivity towards cancer cells vs. normal cells was enhanced upon CMC encapsulation. [ABSTRACT FROM AUTHOR]

A new series of naphthalimide platinum(IV) compounds with dual DNA damage mechanism were designed, synthesized and evaluated for antitumor activities. The platinum(IV) compounds could combine with DNA and cause DNA damage via naphthalimide fragment. Then the platinum(II) complexes released in reductive microenvironment would cause remarkable secondary DNA lesions. Some title compounds exhibit good antitumor activities and are of great potential in overcoming the drug resistance of cisplatin. Furthermore, naphthalimide platinum(IV) complexes could effectively combine with HSA by electrostatic force, which would influence the drug distribution and bioactivities in vivo. Moreover, the accumulation of the tested platinum(IV) compounds in whole cells and DNA is remarkably enhanced in comparison with cisplatin and oxaliplatin. This article describes the design and synthesis of a new series of platinum(IV) compounds with dual DNA damage mechanism. Target compounds exhibited good antitumor activities and were of great potential in overcoming drug resistance. Moreover, they could effectively combine with HSA and further influence the drug distribution and bioactivities in vivo. [ABSTRACT FROM AUTHOR]

In this work the synthesis, photochemistry, and streptavidin interaction of new [Ru(tpy)(bpy)(SRR′)](PF6)2 complexes where the R′ group contains a free biotin ligand, are described. Two different ligands SRR′ were investigated: An asymmetric ligand 1 where the Ru‐bound thioether is a N‐acetylmethionine moiety linked to the free biotin fragment via a triethylene glycol spacer and a symmetrical ligand 2 containing two identical biotin moieties. The coordination of these two ligands to the precursor [Ru(tpy)(bpy)Cl]Cl was studied in water at 80 °C. In such conditions the coordination of the asymmetric ligand 1 occurred under thermodynamic control. After the reaction, a mononuclear and a binuclear complex were isolated. In the mononuclear complex, the ratio of methionine‐ {[6](PF6)2} vs. biotin‐bound {[7](PF6)2} regioisomer was 5.3 and the free biotin fragment of [6](PF6)2 allowed to purify it from its isomer [7](PF6)2 at small scales using avidin affinity chromatography. Coordination of the symmetrical ligand 2 afforded [Ru(tpy)(bpy)(2)](PF6)2 {[8](PF6)2} in synthetically useful scales (100 mg), good yield (82 %), and without traces of the binuclear impurity. In this complex, one of the biotin remains free whereas the second one is coordinated to ruthenium. Photochemical release of ligand 2 from [8](PF6)2 occurred upon blue light irradiation (465 nm) with a photosubstitution quantum yield of 0.011 that was independent of the binding of streptavidin to the free biotin ligand. A new synthetic strategy is presented for preparing photoactivated chemotherapeutic ruthenium compounds functionalized with a free biotin group. The free biotin fragment, which is bound to ruthenium via a thermally stable Ru–S bond, can still bind to streptavidin. Blue light irradiation resulted in the cleavage of the biotin‐bearing protecting ligand, thus liberating the ruthenium aqua compound. [ABSTRACT FROM AUTHOR]

Half‐sandwich organometal complexes of RuII, OsII, RhIII and IrIII with β‐diketone‐like ligands have been extensively explored as potential prodrugs in anticancer therapy in recent years. Here a minireview of this class of compounds is provided. A discussion of the basic structural features of the metal complexes is given, together with their in vitro anticancer activity. [ABSTRACT FROM AUTHOR]

Organometallic N‐heterocyclic carbene (NHC) complexes with intercalating bis‐naphthalimide ligands were prepared and evaluated biologically. Cytotoxic effects against tumor cells or bacteria were strongly ligand dependent with minor influence of the metal (Ag, Ru, Rh, Au) centers. Complex 8b with a rhodium(I) NHC moiety was studied in more detail for its DNA interacting properties in comparison to the metal free ligand. These studies showed a good DNA binding pattern with some preference for the telomeric quadruplex structure hTelo. Complex 8b was also shown to trigger additional coordinative binding to the DNA and therefore represents an useful tool compound with a mixed intercalative/coordinative DNA binding mode. [ABSTRACT FROM AUTHOR]

The current study investigates [Ru(bipy)2(dpphen)]Cl2 [where bipy = 2,2′‐bipyridine and dpphen = 2,9‐diphenyl‐1,10‐phenanthroline] (complex 1) for photoactivatable chemotherapy (PACT) application on five cancer cell lines. [Ru(bipy)2(phen)]Cl2 [where phen = 1,10‐phenanthroline] (complex 2) was included as an unstrained control. Upon excitation with visible light, complex 2 proved to be photostable while complex 1 underwent a quantitative dissociation of the bipy ligand and formation of a RuII polypyridyl aqua complex in water. Complex 1 demonstrated only marginal activity in the dark; its cytotoxicity increased significantly upon photoactivation with a high phototoxicity index (PI = [IC50 dark]/[IC50 light]) ranging from 39.2‐fold in A549 to over 100‐fold in MDA‐MB‐231. Complex 2, on the other hand, did not show much difference in anticancer activity between dark and light conditions. Importantly, the IC50 of the photoproduct of complex 1 was several folds lower than that of cisplatin in all tested cell lines. Furthermore, the dissociating ligand (bipy) was biologically inert in almost all cell lines investigated confirming that phototoxicity was mediated primarily by the Ru aqua complex that is released upon irradiation. In conclusion, the Ru‐centered complex 1 could represent a potential photoactivatable chemotherapeutic drug that increases selectivity to tumors and offers alternative treatment in the light of increasing cisplatin resistance. [ABSTRACT FROM AUTHOR]

Two new platinum(II) complexes bearing triphenylphosphine and bidentate oxime ligands [Pt(Cl)(PPh3){(κ2‐N,O)‐(1{C(R)=N(OH)‐2(O)C10H6})}] (R = H, Me) were synthesized in good yields from trans‐[PtCl(µ‐Cl)(PPh3)]2. The structure of [Pt(Cl)(PPh3){(κ2‐N,O)‐(1{CH=N(OH)‐2(O)C10H6})}] was determined by single‐crystal X‐ray diffraction. Both complexes showed good antiproliferative properties in vitro against HeLa, A2780, and A2780cis cancer cell lines. They reacted cleanly with alkylating agents in the presence of aqueous bases under phase‐transfer catalysis conditions to afford the corresponding O‐alkylation products [Pt(Cl)(PPh3){(κ2‐N,O)‐(1{HC=N(OR′)‐2(O)C10H6})}] [R′ = CH2CH2Cl, CH2Ph, (CH2)4Br] in good yields. [ABSTRACT FROM AUTHOR]

Iron(III) complexes of a vitamin B6 Schiff base and NNN-donor ligands with pendant boron-dipyrromethene (BODIPY) moieties; namely, [Fe(L1-3)(L4,5)](NO3) (1-4), where L¹ is benzyl-bis[(pyridin-2-yl)methyl]methanamine (bzdpa in 1), L² is a noniodinated BODIPY-appended dipicolylamine ligand (in 2, 3), L³ is the diiodinated BODIPY analogue in 4, L4 is a vitamin B6 Schiff base, namely 3-hydroxy-5(hydroxymethyl)-4-{[(2-hydroxyphenyl)imino]methyl}-2-methylpyridine (in 1, 3, and 4), and L5 is 2-[(2-hydroxyphenylimino)-methyl]phenol (in 2) as a nonpyridoxal Schiff base, were prepared, characterized, and their cellular localization and cytotoxic activity in light and in the dark were studied. The diiodo-BODIPY complex 4 displays remarkable photoinduced cytotoxicity in visible light (400-700 nm), with IC50 values within 0.11-0.25 µM and about 200-fold lower dark toxicity. Complex 3, being fluorescent, was used for cellular imaging by confocal microscopy. Complex 4 shows supercoiled pUC19 DNA cleavage activity through the generation of singlet oxygen (¹O2) as the reactive oxygen species (ROS). Selective uptake of the complexes is observed from competitive cellular incorporation assays in cancer and noncancer cells. The complexes also show no apparent toxicity up to 100 µM in the immortal human lung epithelial cells HPL1D in both light and the dark. Complex 3 shows preferential accumulation in lysosomes, giving a Pearson's correlation coefficient value of about 0.7. [ABSTRACT FROM AUTHOR]

In light of the widely used platinum anticancer drugs showing high toxicity and poor selectivity, the quest to develop new anticancer agents is increasing. This study investigated the synthesis of mononuclear and trinuclear RhIII and IrIII sulfonatecontaining pyridinyl complexes that have been fully characterized using NMR and IR spectroscopy, HR-ESI-mass spectrometry and elemental analysis. The cytotoxicities of all sulfonated pyr-idinyl compounds were investigated against a WHCO1 oesophageal cancer cell line and the metal complexes showed moderate activity, while the uncomplexed ligands were inactive. Several of the trinuclear complexes are of comparable activity to that of the clinical cancer drug cisplatin. 1H NMR model studies demonstrated the in vitro DNA binding ability of the most active complex. [ABSTRACT FROM AUTHOR]

A series of five iron(III) complexes, namely [Fe(HL1)Cl2] (1), [Fe(HL2)Cl2]·1.6H2O (2·1.6H2O), [Fe(HL3)(MeOH)Cl2]·0.5H2O (3·0.5H2O), [Fe(HL4)(MeOH)Cl2]·0.5H2O (4·0.5H2O) and [Fe(HL4)(DMF)Cl2]·0.5Et2O·H2O (4′·0.5Et2O·H2O), where H2L1 = l-proline-salicylaldehyde–thiosemicarbazone (l-Pro-STSC), H2L2 = pyrrolidine-substituted l-Pro-STSC, H2L3 = phenyl-substituted l-Pro-STSC, and H2L4 = naphthyl-substituted l-Pro-STSC, have been synthesized. The two ligand precursors (H2L3 and H2L4) and iron complexes were characterized by elemental analysis, spectroscopic methods (UV/Vis, IR, and NMR), ESI mass spectrometry, cyclic voltammetry, and single-crystal X-ray crystallography (1–3 and 4′). Magnetic properties of the five-coordinate complex 2 and six-coordinate complex 4 have also been investigated. The antiproliferative activity of the organic hybrids and their iron(III) complexes have been studied in vitro in five human cell lines and one murine cancer cell line, namely HeLa (cervical cancer), FemX (melanoma), A549 (alveolar basal adenocarcinoma), LS-174 (colon cancer), MDA-MB-453 (breast cancer) and MS1 (transformed murine endothelial), as well as in human noncancerous fetal lung fibroblast cell line (MRC-5). According to the structure–activity relationship, introduction of aromatic groups such as phenyl or naphthyl enhances the cytotoxic potency of the hybrids in the following order H2L1 < H2L2 < H2L3 < H2L4. Coordination of the hybrids to iron(III) improves their antiproliferative activity in the majority of investigated cell lines with exception of H2L3 in LS-174, H2L4 in MS1, and both H2L3 and H2L4 in FemX cell lines, where an opposite effect was observed. [ABSTRACT FROM AUTHOR]

In this work, a new kind of multiple drug-release system, graphene oxide (GO)@polylactic acid (PLA)@hydroxyapatite (HA) composite microcapsule, was constructed through the double Pickering emulsion method. In the preparation of the microcapsules, GO and HA were used as stabilizers for the water-in-oil (W¹/O) and oil-in-water (O/W²) systems, respectively. Furthermore, GO, as the internal water phase (W¹), could carry a hydrophilic drug (5-FU), while PLA, as the oil phase (O), was employed to effectively embed a hydrophobic drug (coumarin). Additionally, the pH-sensitive HA in an external water phase (W²) could also act as a vector to carry hydrophilic rose bengal, due to its excellent adsorption ability. Dynamic optical experiment results show that the uniform size and complete structure of the GO@PLA@HA composite microcapsules can be obtained at a volume ratio of W¹/O/W² = 3:20:100. The pre-pared GO@PLA@HA composite microcapsules present good biocompatible, biodegradable, and pH-sensitive features. The respective drug encapsulation efficiencies of 5-FU, coumarin, and rose bengal are estimated to be 13.38 %, 48.58 %, and 53.24 %, and their loading efficiencies are 0.15 %, 4.49 %, and 5.3 %, respectively. The controlled release of drugs can be realized by the degradation of HA in the simulated acidic tumoral environment, which illustrates the pH-triggered drug-release behavior of HA. More importantly, the above three different drugs, with their hydrophilic or hydrophobic natures, could be loaded into the single W¹@O@W² microcapsule, and they exhibited multistage sustained release in PBS solution at pH 5.0. Thus, the as-synthesized composite microcapsules, with their multistage drug-delivery function, may act as a new and promising drug-delivery system in the medical field. [ABSTRACT FROM AUTHOR]

Dicationic ruthenium(II)-p-cymene complexes containing curcumin ligands (curcH = curcumin, bdcurcH = bisdemethoxycurcumin) and ionic N-methyl-1,3,5-triaza-7-phosphaadamantane [PTA-Me]X (X = BF4 or I) have been synthesized and fully characterized for the first time. The solid-state structure of [Ru(p-cym)(curc)(PTA-Me)][SO3CF3][BF4] has also been determined by single-crystal X-ray diffraction. Modest antiproliferative activities of the complexes were observed against cisplatin-sensitive and cisplatin-resistant human ovarian carcinoma cells (A2780 and A2780cisR, respectively) and nontumorigenic human embryonic kidney (HEK293) cells. [ABSTRACT FROM AUTHOR]

The [Pd(AEMP)Cl2] complex [AEMP = 2-(2-aminoethyl)-1-methylpyrrolidine] was prepared and characterized by single-crystal X-ray diffraction and spectroscopic analyses. The structure of the complex was found to be square-planar with some distortion. The geometric optimizations of the ligand and complex were performed with the DFT/B3LYP method by using Gaussian 09. The stoichiometry and stability constants of the complexes formed in the reaction of [Pd(AEMP)(H2O)2]2+ with dicarboxylic acids and DNA constituents were investigated at 0.1 m ionic strength and 25 °C. The results show that both DNA constituents and cyclobutanedicarboxylate (CBDCA) coordinate to [Pd(AEMP)(H2O)2]2+ to form the quaternary complex [Pd(AEMP)(CBDCA-O)DNA], where CBDCA-O represents cyclobutanedicarboxylate coordinated through one carboxylate oxygen atom to the PdII center. The speciation concentration distributions in solution were evaluated. The biological activity for DNA cleavage and cytotoxicity of the [Pd(AEMP)Cl2] complex was studied. [ABSTRACT FROM AUTHOR]

Vitamin B12 (cyanocobalamin) is a vital nutrient characterized by very low bioavailability. Owing to their extremely high proliferation rates, tumor cells show increased demand for nutrients in comparison with healthy ones, including the greater uptake of vitamin B12. This avidity for cyanocobalamin can thus be exploited for the site-specific delivery of drugs directly into tumor cells by conjugation of vitamin B12 (carrier) to either chemotherapeutic or diagnostic agents. In particular, tailored cobalamin-containing substrates can be conjugated to metal-based drugs to achieve targeted delivery into the affected tissues, thus accomplishing biomolecular recognition and tumor selectivity. Progress in the development of metal-vitamin B12 conjugates for medicinal applications is summarized and discussed. [ABSTRACT FROM AUTHOR]

Molecularly targeted therapeutic agents make up an important class of oncology drugs that are used either alone, or in combination with classical cytotoxic agents, to combat many solid tumors and hematological cancers. Their targets in cancer cells are proteins that are encoded by oncogenes, which regulate cell growth, survival, and proliferation. These include a number of signal-transducing and angiogenesis-related kinases, hormone receptors, and certain cell-surface antigens. Targeting of cancer cells harboring oncogenic molecular targets with precision medicines, while sparing the vast majority of normal healthy cells, has led to promising new treatments for cancer patients. Molecularly targeted therapeutic agents promise higher efficacy and weaker side effects than the traditional cytotoxic chemotherapies. Simple metal complexes and metal-organic hybrid agents have been the subjects of investigation for many years since the success of cisplatin in treating genitourinary cancers, but their applications in targeted therapies remain underexplored. In this review we highlight the development of metal-based targeted cancer therapeutic agents with unique structures and functions. These strategies provide exciting opportunities for discovering new therapeutic and diagnostic agents for clinical uses. [ABSTRACT FROM AUTHOR]

Electron paramagnetic resonance spectroscopy (EPR) is an invaluable method for characterizing ligand environments and oxidation states of paramagnetic metal complexes. In this review we describe applications of this technique to understanding the often complicated mechanisms of metal-based anticancer compounds. EPR has been instrumental in unravelling this in many instances, providing insight into conformations upon dissolution, aqueous ligand exchange, pH effects, and redox processes. EPR studies have also characterized the protein and DNA interactions of metal-based chemotherapeutics, enabling discrimination of different binding modes. EPR can also be used to probe the behaviour of metallodrugs with whole cells, revealing interactions with cellular components and redox stability. Together, these studies provide important information on aspects of anticancer activity and demonstrate the scope and potential of EPR to contribute to the ongoing development of metal-based anticancer complexes. [ABSTRACT FROM AUTHOR]

We present herein the results of a pharmacokinetic (PK) study of CuII mixed-chelate coordination compound CasIII-La {[Cu(5,6-dimethyl-1,10-phenanthroline)(acetylacetonate)(H2O)]NO3}, which belongs to the antineoplastic family of compounds known as Casiopeínas. The main interest in this molecule lies in the big difference in its lethal dose and PK parameters in Wistar rats compared with its structural isomer CasIII-Ea {[Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonate)(H2O)]NO3}. For instance, the half-lives of these compounds are 9.6 ± 1.15 and 48 ± 4.6 h for CasIII-La and CasIII-Ea, respectively. The differences in the half-lives have been attributed to their different capacities to cross cellular membranes. Molecular dynamics studies of a fraction of a cell membrane and Casiopeínas were developed to identify the possible intermolecular interactions responsible for the retention of the compound inside the cellular membrane. Also, quantum theory of atoms-in-molecules studies was developed to determine the capacity of the hydrogen atoms of methyl groups to participate in intermolecular interactions. In addition, peripheral human blood lymphocyte and macrophage samples were used to determine the cross-membrane effect on cytotoxicity. [ABSTRACT FROM AUTHOR]

Among the various applications of metal-based compounds, those that involve catalytic properties and biological activity have been the goals of quests by many research teams throughout the world. We mainly concentrate in this short review article on the anticancer properties of a certain class of organometallic ruthenium compounds: the cyclometalated derivatives that have been studied in the last decade. We emphasize the apparent contradiction between the known reactivity of the carbon-metal bonds in these species towards nucleophilic and electrophilic reagents and the fact that these bonds most probably survive the harsh reaction conditions that exist in most of the catalytic media and probably also in the biologic media. We focus on the mechanisms of action of the cycloruthenated molecules in terms of their anticancer properties and thus reveal some of the most recent findings on the potential modes of action of these compounds in cancer cells, which open new therapeutic perspectives. [ABSTRACT FROM AUTHOR]

[Fe(NCN)2]PF6 ( 1·PF6) [NCHN = 1,3-di(pyridin-2-yl)benzene] was readily obtained by a transmetalation reaction between [Fe3(CO)12] and Hg(NCN)Cl followed by a metathesis reaction with KPF6. X-ray diffraction, electron paramagnetic resonance spectroscopy, and cyclic voltammetry studies confirmed the proposed structure. Cytotoxic assays in human colon cancer (HCT-15), lung cancer (SKLU), and gastric cancer (AGS, KATOIII) cells were performed, and the IC50 data obtained for all cell lines showed that 1·PF6 has a much higher activity than cisplatin. [ABSTRACT FROM AUTHOR]

AuL10 ([AuIIICl2(dmdt)], dmdt = N, N-dimethyldithiocarbamate) and AuL12 ([AuIIIBr2(esdt)], esdt = ethylsarcosine dithiocarbamate) are two extremely promising gold-based anticancer compounds. Their mechanisms of action are still largely unknown although some specific hypotheses have been proposed. To shed light on their reactivity with probable biological targets, we report here on their interactions with serum albumin and calf-thymus DNA, taken as model biomolecules. Quite unexpectedly, spectrophotometric investigations revealed substantially different patterns of interaction for these two gold complexes with the aforementioned biomolecules, probably arising from differences in redox chemistry. Afterwards, AuL12 was tested against A549 human non-small-cell lung carcinoma cells, evaluating its real-time profile of cell-growth inhibition by means of the xCELLigence Real-Time Cell Analysis system. Measures of impedance by non-invasive gold microelectrodes at the base of each well indicated that this gold complex inhibits cell proliferation after only 4 h of treatment, producing its cytotoxic effects probably at the membrane level. [ABSTRACT FROM AUTHOR]

As anticipated in the title, this contribution is basically divided into two, strictly connected, parts. The first is a personal overview of the ruthenium drug candidate NAMI-A, almost 30 years after its synthesis and the discovery of its unprecedented antimetastatic properties in animal models at nontoxic dosages. The sections relating to the chemical and biological behavior of the complex, and the hypotheses on its mechanism(s) of action, are kept to a minimum, whereas more space is devoted to discussion of the results of the clinical investigations. The second part deals in detail with a number of undemonstrated misconceptions (or myths) that, over the years, have thrived around NAMI-A and other ruthenium drug candidates, thus negatively affecting the whole field of Ru anticancer drugs. [ABSTRACT FROM AUTHOR]

The lack of selectivity for cancer cells and the resulting negative impact on healthy tissue is a severe drawback of actual cancer chemotherapy. Tethering of cytotoxic drugs to targeting vectors such as peptides, which recognize receptors overexpressed on the surface of tumor cells, is one possible strategy to overcome such a problem. The pentapeptide cyc(RGDfK) targets the integrin receptor αvβ3, important for tumor growth and metastasis formation. In this work, two terpyridine-based RuII complexes were prepared and for the first time conjugated to cyc(RGDfK) through amide bond formation, which resulted in a monomeric and a dimeric bioconjugate. Both RuII complexes were found to bind strongly and selectively to integrin αvβ3, and the dimeric molecule displayed a 20-fold higher affinity to the receptor than the monomeric one. However, the cytotoxicity of the complexes and related bioconjugates against human A549 and SKOV-3 cell lines is still not sufficient for application as anticancer agents. Nevertheless, considering the high selectivity for integrin receptor αvβ3, the synthesis of Ru-based bioconjugates with cyc(RGDfK) paves a promising way towards the design of effective targeted anticancer agents. [ABSTRACT FROM AUTHOR]

Ru(arene)[3-hydroxy-4(1 H)-pyr(id)one]Cl complexes are known to be converted intodinuclear Ru(arene) compounds with three hydroxido bridges in aqueous solution. In an attempt to obtain anticancer Ru(arene) complexes of 3-hydroxy-4(1 H)-pyr(id)one ligands that are stable in aqueous solution, triphenylphosphine (PPh3) and 1,3,5-triaza-7-phoshatricyclo[3.3.1.1]decane (pta) were introduced as co-ligands instead of the chlorido ligand. This led to a series of cationic complexes that were characterized by using standard methods and X-ray diffraction analysis. The pta complexes were found to be highly stable in aqueous solution for up to 120 h. While they were unreactive in the presence of l-histidine (His) and l-methionine (Met), l-cysteine (Cys) induced cleavage of the 3-hydroxy-4(1 H)-pyr(id)one ligands from the Ru center. In vitro cytotoxicity assays against human cancer cell lines revealed that the complexes with the more lipophilic phosphine ligand were cytotoxic in the low-micromolar concentration range, while the analogous pta compounds did not significantly inhibit cell proliferation. [ABSTRACT FROM AUTHOR]

Photoactivated chemotherapy is gaining increasing interest as a potentially selective treatment of cancer, and bacterial and viral infections. In this approach a therapeutic can be administered as a nontoxic prodrug and then converted to its active form in the diseased tissue by the localized application of light. Here we report the first example of a photolabile ruthenium prodrug that releases a purine ligand when irradiated with visible light. A series of ruthenium(II) polypyridyl complexes were prepared with the anticancer agent 6-mercaptopurine as a ligand. The nature of the polypyridyl ligand was found to strongly influence the properties of the complexes, including absorbance maxima, photostability, and the binding mode of 6-mercaptopurine. The lead complex is stable in solution in the dark but releases 6-mercapoturine when irradiated with visible light, leading to a significant increase in toxicity towards breast cancer cells. [ABSTRACT FROM AUTHOR]

A new family of cytotoxic TiIV complexes is described, based on the salalen (half salan and half salen) ligands. Altogether, 17 (salalen)TiIV complexes with different ligand substitutions and different numbers of labile groups were synthesized. Representative complexes were characterized by X-ray crystallography. The complexes were evaluated for their hydrolytic stability in 10 % D2O solutions, their cytotoxicity toward HT-29 human colon cancer cells, and the retaining of activity after pre-incubation in aquatic medium prior to cell addition. The results showed that: (a) reducing complexes' lability increased hydrolytic stability, (b) bulky groups often increased kinetic stability toward hydrolysis, but also damaged accessibility, (c) for unstable complexes, some hydrolysis products are likely the active species, (d) specific hydrophobic groups may facilitate penetration through the cell membrane, and (e) one di- tert-butylated salalen catecholato complex was identified as the superior derivative, combing high cytotoxicity with high stability and accessibility. [ABSTRACT FROM AUTHOR]

The drawbacks of the platinum chemotherapy agents cisplatin, carboplatin and oxaliplatin have inspired the development of compounds with different mechanisms of action. Polyaromatic platinum complexes (PPCs) are a promising anticancer alternative; these bind reversibly with DNA through the insertion of a planar aromatic moiety between nucleobases in a process known as intercalation. PPCs have demonstrated in vitro behaviour remarkably different from that of cisplatin and exhibited cytotoxicity up to one hundred times higher than that of cisplatin in many cell lines. This microreview primarily discusses 1,10-phenanthroline-based complexes of the type [Pt(PL)(AL)]2+ (where PL is a polyaromatic ligand and AL is an ancillary ligand), including their cytotoxicity, DNA-binding behaviour and biological activity in vitro and in vivo. Other PPCs within the field, including dual-mode DNA binders incorporating tethered acridines and other potently cytotoxic complexes, are also covered. [ABSTRACT FROM AUTHOR]

Vanadium complexes are attractive potential alternatives to platinum-based anticancer drugs. Two vanadium(V) complexes, based on a common chelating tetradentate diaminobis(phenolato) ligand featuring a branched connectivity but differing in their labile ligands, were synthesized and characterized. Whereas the isopropoxido complex was obtained as a mixture of cis and trans isomers with regard to the orientation of the labile group vs. the amine sidearm, the salicylato-containing complex was obtained as a single trans isomer. X-ray structures of the complexes featured octahedral geometry for both. The two complexes exhibited high cytotoxic activity toward different cancer cells, often higher than that of cisplatin, including toward cisplatin-resistant ovarian cancer cells. These complexes demonstrated rapid hydrolysis, releasing the labile ligand within several minutes, with no indications of release of free chelating ligand after water exposure, suggesting that polynuclear hydrolysis products are involved in the cellular activity. [ABSTRACT FROM AUTHOR]

The β-diketone scaffold is a key intermediate in the synthesis of COX-2 inhibitors, a type of non-steroidal anti-inflammatory agents of the coxib family, which have also been shown to have excellent anticancer potential at the preclinical stage of research. Moreover, it is also present in the family of natural products named curcuminoids. Both natural products and their synthetic analogues possess interesting antibacterial, neuroprotective and anticancer properties. Coordination compounds of curcuminoids with platinum-group metals as potential anticancer agents are a hot topic of current research, with most scientific articles on this topic having been published in the last five years. Structurally simpler diketones, such as acetylacetone derivatives, are also employed in the design of new metal-based agents. Most notably, the first metal-based, non-platinum anticancer compound to enter clinical trials was budotitane - cis-diethoxy(1-phenylbutane-1,3-dionato)titanium(IV). Recently, several studies of platinum-group coordination and organometallic compounds, their biological evaluation and mode-of-action studies have been published in high-impact journals in the field of inorganic and medicinal chemistry. [ABSTRACT FROM AUTHOR]

As part of our ongoing study of the toxicity of compounds derived from 1,1-bis(4-hydroxyphenyl)-2-ferrocenylbut-1-ene, we have recently shown that closely analogous [3]ferrocenophane complexes have an in vitro toxicity level substantially higher than that of their ferrocene counterparts, particularly in the case of mono- and diphenol complexes. In this study we have examined whether the presence of a dimethylamino chain, analogous to the chain in hydroxytamoxifen, is capable of producing in the ferrocenophane series the same antiestrogenic effect observed for OH-Tam and Fc-OH-Tam. To this end, we have synthesized and characterized new complexes bearing various side-chains [O(CH2)3NMe2, O(CH2)3piperidine, O(CH2)3pyrrolidine, NHCO(CH2)2NMe2] and studied the biochemical properties of those complexes possessing appropriate solubility. The results revealed that the new complexes of [3]ferrocenophane have very strong antiproliferative effects; one of the compounds bearing an NHCO(CH2)2NMe2 chain has an IC50 value of 0.05 ± 0.02 µ m for MDA-MB-231 breast cancer cells. All the complexes showed affinity for the estradiol receptor. At the low (nanomolar range) concentrations at which the estrogenic/antiestrogenic effect is expressed in these molecules, the presence of an amino-substituted side-chain does not induce in the [3]ferrocenophane series the antiestrogenic effect observed with OH-Tam and Fc-OH-Tam. However, this effect has been found for the complex with a slightly longer chain [O(CH2)4NMe2]. [ABSTRACT FROM AUTHOR]

Self-assembled coordination cages are interesting as drug-delivery systems. Therefore, the synthesis of new M2L4 (M = Pd, Pt) molecular cages derived from highly fluorescent, rigid polyaromatic ligands is reported herein, and the first Pt2L4 cage with a ligand consisting of three pyridine moieties is described. The photophysical properties were examined, and they showed high quantum yields Φ of up to 48 % for the methoxy-functionalized ligands. Coordination of the ligands to palladium and platinum ions did, however, reduce the fluorescence of the metallocages. The host-guest chemistry of the palladium cages with cisplatin was investigated, which confirmed the encapsulation. The cages encapsulating cisplatin show significantly increased cytotoxicity towards A549 (human lung adenocarcinoma) cells relative to that shown by cisplatin and, thus, appear to be promising delivery vectors for the anticancer drug cisplatin. [ABSTRACT FROM AUTHOR]

Antitumor agents, Cobalt, Nanoparticles, Tetrazole carboxylate ligands, Structure elucidation Keywords: Antitumor agents; Cobalt; Nanoparticles; Structure elucidation; Tetrazole carboxylate ligands EN Antitumor agents Cobalt Nanoparticles Structure elucidation Tetrazole carboxylate ligands 1 1 1 12/30/22 20221227 NES 221227 GRAPH. [Extracted from the article]

We have investigated the synergistic effect of nitric oxide and singlet oxygen originating from stimulated ruthenium complexes and their photodynamic action against a melanoma cancer cell line. In aqueous solution, the photosensitizer [Ru(NH3)5pz]2+ ( I; pz = pyrazine) and the nitrosylruthenium complex trans-[RuCl([15]aneN4)NO]2+ ( II; [15]aneN4 = 1,4,8,12-tetrazacyclopentadecane) can produce singlet oxygen and nitric oxide, respectively. The phototoxicity of complex I does not correlate with the singlet oxygen quantum yields unless it is mediated by nitric oxide release from complex II. This effect is around 70 and 50 % higher than the effect prompted by compounds I and II, respectively, in isolation in the presence of light. It was found that the number of hypodiploid cells in the melanoma cancer cells increased, which indicates that a mixture of compounds I and II induces apoptosis of tumorigenic cell lines. Both singlet oxygen and nitric oxide produced by the ruthenium complexes enhance the photodynamic efficacy in melanoma cancer cells. [ABSTRACT FROM AUTHOR]

The nonsteroidal anti-inflammatory drugs (NSAIDs) make up a great group of drugs that provide benefits in the prevention of cancers. Coordinated metal ions with NSAIDs provide advantages over the drugs themselves. The metal complexes of NSAIDs display a range of biological activities quite often inaccessible to the original NSAID ligands. NSAIDs-metal complexes have molecular properties different from those of the parent drugs. Thus, if a given NSAIDs-metal complex remains intact in the biological medium its biological target is almost invariably different from the original NSAID target. This review includes results obtained on the antibacterial and antiproliferative activities of metal-NSAIDs complexes and their interaction with intracellular components. The study shows that the molecular weights of metal complexes containing the same NSAID are linearly related to their IC50 values against MCF-7 cells. Moreover, compounds with low molecular weight strongly bind to DNA. [ABSTRACT FROM AUTHOR]