Jinsung Tae

A Rhodamine−Hydroxamic Acid-Based Fluorescent Probe for Hypochlorous Acid and Its Applications to Biological Imagings

A new rhodamine-hydroxamic acid-based fluorescent chemosensor for the rapid detection of HOCl in aqueous media was developed. The system, which utilizes an irreversible HOCl-promoted oxidation reaction, responds instantaneously at room temperature with linear proportionality to the amount of HOCl. This system is highly selective for HOCl over other reactive oxygen species (ROS) and highly sensitive in aqueous solutions. Biological imaging studies using living cells and organisms (A549 cells and zebrafish) to detect HOCl are successfully demonstrated.

A gold(III) ion-selective fluorescent probe and its application to bioimagings.

A highly selective and sensitive fluorescent chemosensor for Au(3+) has been reported. The system utilizes an irreversible Au(3+)-promoted cyclization reaction of a rhodamine amide tethered with an alkyne. The probe can sense Au(3+) ions selectively over other biologically relevant metal ions, and approximately 50 nM of Au(3+) could be readily detected in aqueous media. Fluorescent imaging of Au(3+) in living cells is also successfully demonstrated.

Synthesis of a highly metal-selective rhodamine-based probe and its use for the in vivo monitoring of mercury.

This protocol describes detailed procedures for the preparation of a rhodamine-based mercury probe and for its applications to the detection of mercury in cells and vertebrate organisms. The mercury probe 1, which is prepared in two steps from rhodamine 6G, responds rapidly to Hg2+ in aqueous solutions with a 1:1 stoichiometry. Owing to the fact that the probe reacts with Hg2+ in an irreversible manner, it has advantages over other reversible mercury probes in in vivo assays with respect to both sensitivity and selectivity. In addition, fluorescent imaging assays of Hg2+ in live cells and zebrafish by using this mercury probe are detailed in this protocol. The approximate time frame for the preparation of the probe is 24 h and for its use in imaging assays is 1.5 h.

Characterization, in vitro cytotoxicity assessment, and in vivo visualization of multimodal, RITC-labeled, silica-coated magnetic nanoparticles for labeling human cord blood-derived mesenchymal stem cells.

UNLABELLED Live imaging is a powerful technique that can be used to characterize the fate and location of stem cells in animal models. Here we investigated the characteristics and in vitro cytotoxicity of human mesenchymal stem cells (MSCs) labeled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate, MNPs@SiO2(RITC). We also conducted various in vivo-uptake tests with nanoparticle-labeled human MSCs. MNPs@SiO2(RITC) showed photostability against ultraviolet light exposure and were nontoxic to human MSCs, based on the MTT, apoptosis, and cell cycle arrest assays. In addition, MNPs@SiO2(RITC) did not affect the surface phenotype or morphology of human MSCs. We also demonstrated that MNPs@SiO2(RITC) have stable retention properties in MSCs in vitro. Furthermore, using optical and magnetic resonance imaging, we successfully detected a visible signal from labeled human MSCs that were transplanted into NOD.CB17-Prkdc(SCID) (NOD-SCID) mice. These results demonstrate that MNPs@SiO2(RITC) are biocompatible and useful tools for human MSC labeling and bioimaging. FROM THE CLINICAL EDITOR The characteristics and in vitro cytotoxicity of human mesenchymal stem cells (MSCs) labeled with silica-coated magnetic nanoparticles incorporating rhodamine B isothiocyanate, RITC were investigated in this study. RITC showed photostability against ultraviolet light exposure and was nontoxic to human MSCs. Using both optical and magnetic resonance imaging, successful detection of signal from labeled human MSCs transplanted into mice is demonstrated.

Rhodamine cyclic hydrazide as a fluorescent probe for the detection of hydroxyl radicals.

A new rhodamine fluorescent probe for monitoring ˙OH has been developed based on the oxidative C-H abstraction reaction of rhodamine cyclic hydrazide. The probe exhibits excellent selectivity for ˙OH with virtually no interference by other ROS/RNS species. Fluorescent imaging of A549 and RAW264.7 cells is also successfully demonstrated to detect intracellular ˙OH in live cells.

Stereocontrolled Preparation of Spirocyclic Ethers by Intramolecular Trapping of Oxonium Ions with Allylsilanes

The stereoselectivity of the spontaneous intramolecular cyclization of 2-(benzenesulfonyl)-2-(4-((trimethylsilyl)methyl)-4-pentenyl)tetrahydropyrans substituted by alkyl groups at various ring positions has been examined. For the 4- and 6-methyl derivatives, formation of the spirocyclic center occurs exclusively anti to the methyl. The outcome in the 5-methyl example is a 3.7:1 syn/anti split. For the trans-4,6-dimethyl derivative, the substituents act in a reinforcing manner and direct cyclization uniquely in one direction. Both the cis and trans bicyclic ethers ring close on that pi-surface of the intermediate oxonium ion syn to the angular hydrogen. The results are rationalized in terms of the predilection of the associated oxonium ions for nucleophilic capture via a chairlike or twist-boat transition state.

Structure-based optimization and biological evaluation of trisubstituted pyrazole as a core structure of potent ROS1 kinase inhibitors

Recently inhibition of ROS1 kinase has proven to be a promising strategy for several indications such as glioblastoma, non-small cell lung cancer (NSCLC), and cholangiocarcinoma. Our team reported trisubstituted pyrazole-based ROS1 inhibitors by which two inhibitors showed good IC₅₀ values in enzyme-based screening. To develop more advanced ROS1 inhibitors through SAR this trisubstituted pyrazole-based scaffold has been built. Consequently, 16 compounds have been designed, synthesized and shown potent IC₅₀ values in the enzymatic assay, which are from 13.6 to 283 nM. Molecular modeling studies explain how these ROS1 kinase inhibitors revealed effectively the key interactions with ROS1 ATP binding site. Among these compounds, compound 9a (IC₅₀=13.6 nM) has exerted 5 fold potency than crizotinib and exhibited high degree of selectivity (selectivity score value=0.028) representing the number of non-mutant kinases with biological activity over 90% at 10 μM.

Unusual O-conjugate addition reactions of β-ketoesters and 1,3-diketones to ethyl propynoate: applications to the synthesis of furans

Abstract Divinyl ethers were synthesized from 1,3-dicarbonyl compounds. Reactions of β-ketoesters and 1,3-diketones with ethyl propynoate in the presence of N -methylmorpholine produced unusual O -conjugate addition products in good yields. The divinyl ethers derived from 1,3-diketones were utilized for the synthesis of 2,3,5-trisubstituted furans under the standard radical cyclization conditions.

Synthesis of aminoquinazoline derivatives and their antiproliferative activities against melanoma cell line.

The synthesis of a novel series of aminoquinazoline derivatives 1a-r and their antiproliferative activities against A375 human melanoma cell line were described. Among them, six compounds showed superior antiproliferative activities to Sorafenib as a reference compound. In particular, the representative compound 1q bearing chromen-4-one moiety exhibited excellent antiproliferative activity (IC(50)=0.006 μM) and good selectivity over HS27 fibroblast cell line.

Isoindol-1,3-dione and isoindol-1-one derivatives with high binding affinity to β-amyloid fibrils

Based on the structural features of Indoprofen and PIB, a series of isoindol-1,3-diones 1a-k and isoindol-1-ones 2a-l were designed and synthesized. These 23 compounds were evaluated by competitive binding assay against aggregated Abeta42 fibrils using [(125)I]TZDM. All the isoindolone derivatives showed very good binding affinities with K(i) values in the subnanomolar range (0.42-0.94 nM). Among them, isoindol-1,3-diones 1i and 1k and isoindol-1-ones 2c and 2i exhibited excellent binding affinities (K(i)=0.42-0.44 and 0.46-0.49 nM) than those of Indoprofen (K(i)=0.52 nM) and PIB (K(i)=0.70 nM). These results suggest that isoindolones could be served as a scaffold for potential AD diagnostic probes to monitor Abeta fibrils.