Anti-trypanosomal activity of doubly modified salinomycin derivatives

Abstract: As a group of biologically active compounds, polyether antibiotics (ionophores) show a broad spectrum of interesting pharmacological properties, ranging from anti-bacterial to anti-cancer activities. There is increasing evidence that ionophores, including salinomycin (SAL), and their semi-synthetic analogues are promising candidates for the development of drugs against parasitic diseases. Our previous studies have shown that esterification and amidation of the C1 carboxylate moiety of SAL provides compounds with potent activity against Trypanosoma brucei, protozoan parasites responsible for African trypanosomiasis. In this paper, we present the synthetic pathways, crystal structures and anti-trypanosomal activity of C1 esters, amides and hydroxamic acid conjugates of SAL, its C20-oxo and propargylamine analogues as well novel C1/C20 doubly modified derivatives. Evaluation of the trypanocidal and cytotoxic activity using bloodstream forms of Trypanosoma brucei and human myeloid HL-60 cells revealed that the single-modified C20-oxo and propargylamine precursor molecules 10 and 16 were the most anti-trypanosomal and selective compounds with 50% growth inhibition (GI50) values of 0.037 and 0.0035 µM, and selectivity indices of 252 and 300, respectively. Also the salicylhydroxamic acid conjugate of SAL (compound 9) as well as benzhydroxamic acid and salicylhydroxamic acid conjugates of 10 (compounds 11 and 12) showed promising trypanocidal activities with GI50 values between 0.032 to 0.035 µM but less favorable selectivities. The findings confirm that modification of SAL can result in derivatives with improved trypanocidal activity that might be interesting lead compounds for further anti-trypanosomal drug development

Sensitizing, sensing and chemical separation of Tb(III) ions: All in a novel T copper metal-organic framework

The importance of rare earth elements in high-tech materials has promoted the necessity to develop new materials for sensing and separating them. Luminescent metal-organic frameworks (MOFs) due to their promising applications as functional materials for chemical sensing and separation, which upon introducing analytes create multi-responsive systems, have been receiving great attention by scientists. In this regard, we have designed and synthesized a novel three-dimensional copper framework, [Cu2(3,4-pydc)2(H2O)5]n.2nH2O (1; 3,4-H2pydc = 3,4-pyridine dicarboxylic acid), in ambient condition with an interesting topology and potential application as a cation exchange material. Upon Tb3+ ions uptake, compound 1 exhibited the antenna effect to sensitize Tb3+ ions and its fluorescent emission was enhanced. It also showed selective sensing ability based on turn-on fluorescence response towards Tb3+ ions, in a mixture of main and transition metal ions and Tb3+ ions. Furthermore, the results showed that the Tb3+ ion exchange process is reversible. Therefore, compound 1 is a promising multifunctional luminescent MOF for simultaneous sensing and chemical separation of Tb3+ ions which is an advantage over the previously used MOFs in this regard. Furthermore, the reusability experiment demonstrated that 1 can be utilized for long-term detection and separation of Tb3+ ions

Sensitizing, sensing and chemical separation of Tb(III) ions: All in a novel T copper metal-organic framework

The importance of rare earth elements in high-tech materials has promoted the necessity to develop new materials for sensing and separating them. Luminescent metal-organic frameworks (MOFs) due to their promising applications as functional materials for chemical sensing and separation, which upon introducing analytes create multi-responsive systems, have been receiving great attention by scientists. In this regard, we have designed and synthesized a novel three-dimensional copper framework, [Cu2(3,4-pydc)2(H2O)5]n.2nH2O (1; 3,4-H2pydc = 3,4-pyridine dicarboxylic acid), in ambient condition with an interesting topology and potential application as a cation exchange material. Upon Tb3+ ions uptake, compound 1 exhibited the antenna effect to sensitize Tb3+ ions and its fluorescent emission was enhanced. It also showed selective sensing ability based on turn-on fluorescence response towards Tb3+ ions, in a mixture of main and transition metal ions and Tb3+ ions. Furthermore, the results showed that the Tb3+ ion exchange process is reversible. Therefore, compound 1 is a promising multifunctional luminescent MOF for simultaneous sensing and chemical separation of Tb3+ ions which is an advantage over the previously used MOFs in this regard. Furthermore, the reusability experiment demonstrated that 1 can be utilized for long-term detection and separation of Tb3+ ions

Synthesis and temperature-dependent studies of a perovskite-like manganese formate framework templated with protonated acetamidine

We report the synthesis, crystal structure, thermal, dielectric, phonon and magnetic properties of the [CH3C(NH2)2][Mn(HCOO)3] (AceMn) compound. Our results show that this compound crystallizes in the perovskite-like orthorhombic structure, space group Imma. It undergoes a structural phase transition at 304 K into a monoclinic structure, space group P21/n. X-ray diffraction, dielectric, IR and Raman studies show that the ordering of the acetamidinium cations triggers the phase transition. Low-temperature magnetic studies show that this compound exhibits weak ferromagnetic properties below 9.0 K

Trinuclear Cage-Like ZnII Macrocyclic Complexes: Enantiomeric Recognition and Gas Adsorption Properties

Three zinc(II) ions in combination with two units of enantiopure 3+3 triphenolic Schiff base macrocycles 1, 2, 3 or 4 form cage-like chiral complexes. The formation of these complexes is accompanied by the enantioselective self-recognition of chiral macrocyclic units. The X-ray crystal structures of these trinuclear complexes show hollow metal-organic molecules. In some crystal forms, these barrel-shaped complexes are arranged in a window-to-window fashion which results in formation of 1-D channels and combination of intrinsic porosity with extrinsic porosity. The microporous nature of the [Zn312] complex is reflected in its N2, Ar, H2 and CO2 adsorption properties. The N2 and Ar adsorption isotherms showed pressure gating behaviour which is without precedent for any noncovalent porous material. The comparison of the structures of the [Zn312] and [Zn332] complexes with that of the free macrocycle H31 reveals a striking structural similarity. In the latter compound two macrocyclic units stitched together by hydrogen bonds form a cage very similar to that formed by two macrocyclic units stitched together by Zn(II) ions. This structural similarity is manifested also by the gas adsorption properties of the free H31 macrocycle. Recrystallization of [Zn312] in the presence of racemic 2-butanol results in enantioselective binding of the (S)-2-butanol inside the cage via coordination to one of Zn(II) ions.This work was supported by the NCN (NarodoweCentrumNauki, Poland) (grant 2011/03/B/ST5/01060).D.P.and J.L.thank the FNP Program“Mistrz” for financial support, and D.F.-J. thanks the Royal Society for funding through a University Research Fellowship.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/chem.20150347

Dopamine sensing based on ultrathin fluorescent metal−organic nanosheets

The importance of dopamine (DA) detection as a biomarker for several diseases, especially Parkinson''s disease, has persuaded scientists to develop new nanomaterials for efficient sensing of DA in clinical samples. Ultrathin metal-organic nanosheets due to their exceptional thickness, large surface area, and flexibility are endowed with many accessible active sites and optimal surface interaction with the target analyte molecules. In this regard, a novel layered fluorescent metal-organic nanomaterial with a honeycomb topology based on europium, [Eu(pzdc)(Hpzdc)(H2O)]n (ECP) (H2pzdc = 2,3-pyrazine dicarboxylic acid), was synthesized. X-ray crystallography revealed that the 3D supramolecular architecture of ECP is constructed from noncovalent interactions of coordinated water molecules between the 2D layers along the b axis. These layers that are only ∼4 nm thick were conveniently separated through ultrasound-induced liquid phase exfoliation. Optical studies show that the reduction of ECP thickness enhances the fluorescence intensity and serves as an efficient optical marker for DA detection. ECP nanoflakes exhibited fast response and high selectivity for DA detection in clinical samples. Good linearity for DA detection in the range of 0.1-10 μM with a detection limit of 21 nM proves the potential of ECP nanoflakes in DA sensing applications

Cathecol and Naphtol groups in Salphen-Type Schiff Bases for the preparation of polynuclear complexes

In this paper, we show a strategy to modify salphen-type Schiff base ligands with naphtol (SYML1) and pyrocathecol (2,3-dihydroxyphenyl) groups (SYML2), or a combination of both (ASYML). Each of these ligands can be used to obtain polynuclear metal complexes following two different strategies. One relies on using metals that are either too large for the N2O2 cavity or not fond of coordination number 4 and the other one relies on forcing the polynuclear species by adding functional groups to the hydroxybenzaldehayde in order to have extra coordination sites in the ligand. We report and characterize the mononuclear complexes SYML1-Cu and SYML1-Ce, along with the dinuclear complex SYML1-Fe and the tetranuclear species SYML2-Mn. The asymmetric ligand ASYML routinely hydrolyzes into the symmetric ligands in the reaction mixtures. SYML1-Fe displays a nearly linear Fe-O-Fe bridge with very strong antiferromagnetic coupling between the Fe(III) ions

Ultrasound-assisted exfoliation of a layered 2D coordination polymer with HER electrocatalytic activity

Altres ajuts: the ICN2 is funded by the CERCA programme/Generalitat de Catalunya. Noemí Contreras Pereda's project that gave rise to these results received the support of a fellowship from "laCaixa" Foundation (ID 100010434). The fellowship code is LCF/BQ/ES17/11600012. Renhao Dong acknowledgements the financial support DFG project (SPP 1928, COORNETs).Large blue rectangular crystals of the 2D layered coordination polymer 1 have been obtained. The interest for this complex is two-fold. First, complex 1 is made of 2D layers packing along the (0-11) direction favored by the presence of lattice and coordinated water molecules. And second, nanostructures that could be derived by delamination are potentially suitable for catalytic purposes. Therefore it represents an excellent example to study the role of interlayer solvent molecules on the ultrasound-assisted delamination of functionally-active 2D metal-organic frameworks in water, a field of growing interest. With this aim, ultrasound-assisted delamination of the crystals was optimized with time, leading to stable nanosheet colloidal water suspensions with very homogeneous dimensions. Alternative bottom-up synthesis of related nanocrystals under ultrasound sonication yielded similar shaped crystals with much higher size dispersions. Finally, experimental results evidence that the nanostructures have higher catalytic activities in comparison to their bulk counterparts, due to larger metallic center exposition. These outcomes confirm that the combination of liquid phase exfoliation and a suitable synthetic design of 2D coordination polymers represents a very fruitful approach for the synthesis of functional nanosheets with an enhancement of catalytic active sites, and in general, with boosted functional properties

The evaluation of the healing of fresh arterial allografts in infected environments

Wstęp. Celem pracy była ocena wgajania materiału tkankowego (allograftu tętniczego) w masywnym zakażeniu protezy naczyniowej. Materiał i metody. Badaniem objęto 50 chorych z infekcją protezy naczyniowej w odcinku aortalno-biodrowo- udowym leczonych wymianą zakażonej protezy na homograft tętniczy. Badania wykonywano w Katedrze i Klinice Chirurgii Naczyniowej, Ogólnej i Transplantacyjnej AM we Wrocławiu w latach 1999-2004. Allograft przechowywano metodą zimnego niedokrwienia w temp. +4°C, w płynie konserwującym (świeży homograft tętniczy). Zakażenie i wgajanie homogarftu diagnozowano za pomocą Duplex-Doppler i scyntygrafii leukocytami znakowanymi Technetem 99m. W obserwacji pooperacyjnej chorych podzielono na dwie grupy: w grupie I po zabiegu operacyjnym zastosowano immunosupresję (24 pacjentów), natomiast w grupie II nie podano tych leków (26 chorych).Wyniki. W grupie osób leczonych pooperacyjnie lekami immunosupresyjnymi (grupa I) nie obserwowano powikłań w postaci pęknięcia przeszczepu związanego z degradacją jego ściany. W grupie chorych niestosujących leków obniżających odporność (grupa II) występowały powikłania związane z uszkodzeniem ściany allograftu pęknięcie, zakrzepica homograftu i tętniak prawdziwy. W obu grupach w badaniu scyntygraficznym odnotowano ustępowanie infekcji po wymianie protezy na homograft tętniczy. Wniosek. Zastosowanie świeżych homograftów tętniczych w leczeniu chorych z zakażeniami protez naczyniowych z protekcją immunosupresji jest właściwą metodą terapeutyczną.Background. In this paper, 50 cases of massive aorto-ilio-femoral graft infection treated by the replacement of infected prosthesis with arterial homograft in the Departament of Vascular, General and Transplantation Surgery In Wrocław University of Medicine during the years 1999–2003 are presented. Material and methods. The arterial allograft was stored with the application of cold ischemia method in a preservation solution at 4°C. Duplex-Doppler Ultrasound and scintigraphy with the use of technetiumlabelled leukocytes were used in the diagnostic evaluation of infection and of the healing process of the homograft. During the follow up period, patients in whom fresh homografts were used were divided into two groups: group I received immunosuppressive regimen after surgery (24 patients) and group II received no immunosuppression (26 patients). Results. In group I, no complications due to the homograft's wall degradation (e.g. graft rupture) were noticed. In group II, complications related to the impairment of the allograft wall were observed: graft rupture, true graft aneurysm and homograft thrombosis. In all groups the regression of infection after in-situ replacement of the synthetic prosthesis with the homograft was monitored with scintigraphy examination. Conclusion. The use of arterial homograft with the application of cold ischemia method and immunosuppression in the therapy of prosthetic graft infection is a proper treatment method