Mesoporous silica and chitosan based pH-sensitive smart nanoparticles for tumor targeted drug delivery

This study investigated inclusion formation and the physicochemical properties of naringin/cyclodextrin through a combined computational and experimental approach. Molecular dynamics simulations were applied to investigate the thermodynamics and geometry of naringin/cyclodextrin cavity docking. The complexes were investigated by UV, FT-IR, DSC, XRD, SEM, 2D-NOSEY and ¹H-NMR analyses. Clearly visible protons belonging to naringin and chemical shift displacements of the H3 and H5 protons in cyclodextrin were anticipated in the formation of an inclusion complex. Naringin solubility increased linearly with increasing cyclodextrin concentration (displaying an A_L profile). The simulations indicated that the phenyl group of naringin was located deep within the cyclodextrin cavity, while the glycoside group of naringin was on the plane of the wider rim of cyclodextrin. The simulation and molecular modeling results indicate that (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) provided the more stable inclusion complex. This result was also in good concordance with the stability constants that had been determined by the phase solubility method. The consistency of the computational and experimental results indicates their reliability.     

In vitro and in vivo antitumor activity of novel 3D-organotin supramolecular coordination polymers based on CuCN and pyridine bases

Two novel organotin supramolecular coordination polymers (SCP), namely, ³_∞[Me₃SnCu(CN)₂·(EN)₂], 1 and ³_∞[Ph₃SnCu(CN)₂·(3-mpy)₂], 2 are obtained by the reactions of K₃[Cu(CN)₄], ethyl nicotinate (EN) or 3-methylpyridine (3-mpy) and Me₃SnCl or Ph₃SnCl in H₂O/acetonitrile solution at room temperature. 2D-layers are constructed via H-bonds between the parallel 1D-puckered chains which contain nanometer-sized [-CN(R₃Sn)NC-] spacers connecting the tetrahedral (T-4) copper sites. The network structures of 1 and 2 consist of infinite layers connected by interlayer H-bonds forming 3D-framworks. 2 is the first compound in this family containing the Ph₃Sn cation. The electronic absorption spectra of 1 and 2 reveal a broad band at 320 nm due to CT transition while the emission spectra exhibit high energy bands at 400-460 nm due to metal-centered (MC) transitions and low energy bands at 485-530 nm corresponding to MLCT. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to determine the in vitro antitumor effects of the SCP 1 and 2 on human breast cancer cell line, ZR-75-1. Cell cycle analysis revealed that the SCP 1 and 2 induced apoptosis in ZR-75-1 breast cancer cell line through activating caspase-3. Moreover, in vivo model, the compound SCP 2 suppressed tumor growth developed mammary carcinoma by 52.3%. Taken together, our novel compounds selectivity exhibit specific in vivo and in vitro antitumor effects.     

Biogenesis of the unique 4',5'-dehydronucleoside of the uridyl peptide antibiotic pacidamycin

The pacidamycins belong to a class of antimicrobial nucleoside antibiotics that act by inhibiting the clinically unexploited target translocase I, a key enzyme in peptidoglycan assembly. As with other nucleoside antibiotics, the pacidamycin 4',5'-dehydronucleoside portion is an essential pharmacophore. Here we show that the biosynthesis of the pacidamycin nucleoside in Streptomyces coeruleorubidus proceeds through three steps from uridine. The transformations involve oxidation of the 5'-alcohol by Pac11, transamination of the resulting aldehyde by Pac5, and dehydration by the Cupin-domain protein Pac13.     

Antenna behavior of donor–acceptor dye‐loaded novel supramolecular framework hosts

New guest dye cations within the channel cavities of supramolecular hosts are studied. The guest organic dyes are intercalated in the supramolecular hosts by a coprecipitation reaction to give new dye‐sensitizer coordination polymers. The absorption spectra for the dye molecules within the supramolecular hosts show intense bands in the region from 500 to 700 nm due to the presence of the dyes within the parallel channels in the monomeric forms. The properties of the resulting colored polymers were investigated by IR, UV–vis, fluorescence spectra and X‐ray powder diffraction, indicating the excitation energy transfer from neutral red or pyronine as donors to methylene blue or thionine as acceptors within a supramolecular system filled with a mixture of both dyes. The wide‐ranging tenability of these highly organized materials offers fascinating new possibilities for exploring excitation energy transfer phenomena, and challenges for developing new photonic devices. Copyright © 2005 John Wiley & Sons, Ltd.     

Synthesis of a homologous 3beta-hydroxycard-5,22-dienolide (author's transl)]

Synthesis of a homologous 3β-hydroxycard-5,22-dienolide. We describe the synthesis of 4′-[(3β-hydroxy-androst-5-en-17β-yl)methyl]-2′(5′)-furanone ( 22 ) starting from 3β-acetoxy-androst-5-ene-17β-carboxylic acid ( 5 ).     

Integrals involving products of bessel functions

Summary The integrals and , where n is any positive integer, are evaluated in terms ofMacRobert E-functions and generalized hypergeometric functions.     

Multiple integrals involving product of modified Bessel functions of the second kind

The following two multiple integrals are evaluated

$$\prod\limits_{r = 1}^{m - 1} {\int\limits_0^\infty {\lambda _r^{k_r } K_{\gamma r} (\lambda _r )d\lambda _r K_\mu } \left[ {x\left( {\lambda _1 ...\lambda _{m - 1} } \right)^{ \pm 1} } \right].} $$     

<Emphasis Type="Italic">In situ</Emphasis> Oxidation of phenol and <Emphasis Type="Italic">o</Emphasis>-aminophenol in the channels of 3d-supramolecular coordination polymers

The host attractive properties of supramolecular coordination polymers of the type _￥³ _\infty^3 [(R₃Sn)₃FeIII(CN)₆], where R = methyl (I), n-butyl (II), and phenyl (III), afford the ability to be used as effective oxidizing reagents for phenol and o-aminophenol forming new host-guest supramolecular coordination polymers. Phenol was oxidized to 1,4-benzoquinone while o-aminophenol was oxidized to poly-o-aminophenol by the polymers I and II and to 2-aminophenoxazin-3-one by the polymer III. The oxidation products were investigated by methods of spectroscopy and high-performance liquid chromatography. The redox reactions were characterized by first-order kinetics. Moreover, mechanisms of the oxidation processes of phenol and o-aminophenol have been proposed.     

Radiophotosynthesis of some 14C-labelled Amino Acids using the Unicellular Green Alga Scenedesmus acutus

Radiophotosynthesis has been carried out using the unicellular green algea Scenedesmus acutus grown, as a substrate for preparing some carbon-14 labelled amino acids. Gaseous ¹⁴CO₂, in an air tight photosynthesis chamber or NaH¹⁴CO₃ solution, in an ordinary photosynthesis chamber, were used as radioactive carbon sources. The yields, radiochemical yields and specific activities of the formed radioactive products are reported in both cases. The results obtained clearly showed the advantages of using the NaH¹⁴CO₃ method. In that case the process was by far less tedious. Moreover, the chemical and radiochemical yields of the formed amino acids were relatively much more higher than the values obtained on using ¹⁴CO₂ in the tight photosynthesis chamber.     

Design and Synthesis of Imidazole and Triazole Pyrazoles as Mycobacterium Tuberculosis CYP121A1 Inhibitors

The emergence of untreatable drug-resistant strains of Mycobacterium tuberculosis is a major public health problem worldwide, and the identification of new efficient treatments is urgently needed. Mycobacterium tuberculosis cytochrome P450 CYP121A1 is a promising drug target for the treatment of tuberculosis owing to its essential role in mycobacterial growth. Using a rational approach, which includes molecular modelling studies, three series of azole pyrazole derivatives were designed through two synthetic pathways. The synthesized compounds were biologically evaluated for their inhibitory activity towards M. tuberculosis and their protein binding affinity (K_D). Series 3 biarylpyrazole imidazole derivatives were the most effective with the isobutyl ( 10 f ) and tert-butyl ( 10 g ) compounds displaying optimal activity (MIC 1.562 μg/mL, K_D 0.22 μM ( 10 f ) and 4.81 μM ( 10 g )). The spectroscopic data showed that all the synthesised compounds produced a type II red shift of the heme Soret band indicating either direct binding to heme iron or (where less extensive Soret shifts are observed) putative indirect binding via an interstitial water molecule. Evaluation of biological and physicochemical properties identified the following as requirements for activity: LogP >4, H-bond acceptors/H-bond donors 4/0, number of rotatable bonds 5–6, molecular volume >340 ų, topological polar surface area <40 Ų.