Novel Imidazopyridine Derivatives Possess Anti-Tumor Effect on Human Castration-Resistant Prostate Cancer Cells.

Prostate cancer (PCa) is the second leading cause of cancer-related death afflicting United States males. Most treatments to-date for metastatic PCa include androgen-deprivation therapy and second-generation anti-androgens such as abiraterone acetate and enzalutamide. However, a majority of patients eventually develop resistance to these therapies and relapse into the lethal, castration-resistant form of PCa to which no adequate treatment option remains. Hence, there is an immediate need to develop effective therapeutic agents toward this patient population. Imidazopyridines have recently been shown to possess Akt kinase inhibitory activity; thus in this study, we investigated the inhibitory effect of novel imidazopyridine derivatives HIMP, M-MeI, OMP, and EtOP on different human castration-resistant PCa cells. Among these compounds, HIMP and M-MeI were found to possess selective dose- and time-dependent growth inhibition: they reduced castration-resistant PCa cell proliferation and spared benign prostate epithelial cells. Using LNCaP C-81 cells as the model system, these compounds also reduced colony formation as well as cell adhesion and migration, and M-MeI was the most potent in all studies. Further investigation revealed that while HIMP primarily inhibits PCa cell growth via suppression of PI3K/Akt signaling pathway, M-MeI can inhibit both PI3K/Akt and androgen receptor pathways and arrest cell growth in the G2 phase. Thus, our results indicate the novel compound M-MeI to be a promising candidate for castration-resistant PCa therapy, and future studies investigating the mechanism of imidazopyridine inhibition may aid to the development of effective anti-PCa agents.

Concentration-driven phase control for low temperature synthesis of phase-pure anatase and rutile titanium oxide.

It is highly desirable to develop controlled synthetic methods at low temperature (<100 °C) for defined phases of titanium oxide nanoparticle. We present here a simple low temperature approach which is based on the peroxide route. This approach allows the preparation of phase-pure rutile and anatase without the use of any additives or surfactants or external acids. The formation of crystalline phases is found to be dependent on reaction temperature and highly dependent on concentration. Phase-pure rutile is obtained in two concentration zones while phase-pure anatase is obtained in one concentration zone. The relationship between phases and reaction conditions (concentration and temperature) fits well with the nucleation diffusion rate model.

Low temperature fabrication & photocatalytical activity of carbon fiber-supported TiO2 with different phase compositions.

Crystalline TiO2 nanoparticles with different phase compositions were fabricated on carbon fibers. The fabrication is achieved at low temperature. The process includes the treatment of Ti(OH)4 with hydrogen peroxide in the presence of carbon fibers. Neither additional acids nor bases, or additives are used during the process. Carbon fibers prior to and after TiO2 loading are characterized by FE-SEM, XRD, and UV-vis absorption spectroscopy. The photocatalytic activity was assessed via photocatalytic degradation of methyl orange solution, and found to be phase composition-dependent & pH dependent. Carbon fibers loaded with mixed-phase TiO2 led to the best photocatalytic performance. HRTEM reveals the anatase/rutile heterojunction which helps explain the high efficiency of photocatalysis. They have been demonstrated to be re-usable in the continuous photocatalytic degradation process.

Antiproliferative activity of novel imidazopyridine derivatives on castration-resistant human prostate cancer cells.

Metastatic prostate cancer (mPCa) relapses after a short period of androgen deprivation therapy and becomes the castration-resistant prostate cancer (CR PCa); to which the treatment is limited. Hence, it is imperative to identify novel therapeutic agents towards this patient population. In the present study, antiproliferative activities of novel imidazopyridines were compared. Among three derivatives, PHE, AMD and AMN, examined, AMD showed the highest inhibitory activity on LNCaP C-81 cell proliferation, following dose- and time-dependent manner. Additionally, AMD exhibited significant antiproliferative effect against a panel of PCa cells, but not normal prostate epithelial cells. Further, when compared to AMD, its derivative DME showed higher inhibitory activities on PCa cell proliferation, clonogenic potential and in vitro tumorigenicity. The inhibitory activity was apparently in part due to the induction of apoptosis. Mechanistic studies indicate that AMD and DME treatments inhibited both AR and PI3K/Akt signaling. The results suggest that better understanding of inhibitory mechanisms of AMD and DME could help design novel therapeutic agents for improving the treatment of CR PCa.

The fast removal of low concentration of cadmium(II) from aqueous media by chelating polymers with salicylaldehyde units.

Poly[4-(4-vinylbenzyloxy)-2-hydrobenzaldehyde], PVBH, a salicylaldehyde chelating functional group-based polymer has been found to be capable of the removal of low concentration of cadmium metal ion in ppb level from aqueous media. The adsorption fits best with the Langmuir model, indicating the monolayer coverage of the metal ion on the surface of chelating polymer. The R(L) values have indicated the favorable adsorption in the range of all the ppb concentrations studied. The kinetic study has revealed a very fast adsorption process with the rate following the pseudo-second-order.

Highly efficient and direct heterocyclization of dipyridyl ketone to N,N-bidentate ligands.

[reaction: see text] Reaction of various aromatic aldehydes with 2,2'-dipyridyl ketone and ammonium acetate in hot acetic acid provides ready access to a series of substituted 1-pyridylimidazo[1,5-a]pyridines, a class of ligands possessing an N,N-bidentate feature, in good yields.

Y-shaped two-photon absorbing molecules with an imidazole-thiazole core.

Two new classes of two-photon absorbing Y-shaped molecules have been developed to possess an imidazole-thiazole core and a stilbene-type conjugation pathway with either nitro or sulfonyl as terminal electron-accepting group.

Convenient preparation of a novel class of imidazo[1,5-a]pyridines: decisive role by ammonium acetate in chemoselectivity.

A facile and one-pot straightforward methodology has been developed to prepare a novel class of imidazo[1,5-a]pyridines. A key role played by ammonium acetate in chemoselectivity has been examined.

Crystal structure of 4,5-bis(4-dimethylaminophenyl)-2-(4-nitrophenyl)imidazole.

A nonlinear optical chromophore, 4,5-bis(4-dimethylaminophenyl)-2-(4-nitrophenyl)imidazole, was investigated by X-ray crystallography. The study focused on coplanarity among several aromatic rings, including phenyls and imidazole. Two phenyl rings with NMe2 groups are twisted by 46.39(3) degrees from each other. However, they are twisted by 23.05(5) degrees and 46.84(3) degrees from the imidazole, respectively. These unequal twists were elucidated by different conjugation pathways from the donors to the acceptor. The phenyl ring with the NO2 group is twisted by only 6.76(6) degrees from the imidazole.

Tertiary pentyl groups enhance salen titanium catalyst for highly enantioselective trimethylsilylcyanation of aldehydes.

tert-Pentyl groups are recognized to be highly effective steric groups that can enhance enantioselectivity of salen titanium complexes when they are used in asymmetrical cyanation of aromatic aldehydes. High ee (92-97%) has been obtained with several aldehyde substrates. Compared to its tert-butyl analogue, the tert-pentyl group has been found to improve enantioselectivity and in some cases quite dramatically.