변영주 교수

Novel 3-carboranyl thymidine analogues (3CTAs) were synthesized as potential boron delivery agents for boron neutron capture therapy (BNCT). This library includes six zwitterionic NH(3)(+)-nido-m-carborane-substituted thymidine analogues (Thds) and the corresponding neutral NH(2)-closo-m-carborane-substituted counterparts. All compounds of this library were good substrates for recombinant human thymidine kinase 1 (TK1) with phosphorylation rates up to 89% relative to that of Thd. One compound ou

Pseudomonas aeruginosa is a causative agent of chronic infections in immunocompromised patients. Disruption of quorum sensing circuits is an attractive strategy for treating diseases associated with P. aeruginosa infection. In this study, we designed and synthesized a series of gingerol analogs targeting LasR, a master regulator of quorum sensing networks in P. aeruginosa. Structure-activity relationship studies showed that a hydrogen-bonding interaction in the head section, stereochemistry and

3-[5-{2-(2,3-Dihydroxyprop-1-yl)-o-carboran-1-yl}pentan-1-yl]thymidine (compound 1, N5-2OH) belongs to a novel class of boron delivery agents for neutron capture therapy, which was designated 3-carboranylthymidine analogue (3CTAs). Two shorter and more convenient synthetic routes were developed for the synthesis of 1 in the 10B-enriched form, which is necessary for its preclinical and clinical evaluation in neutron irradiation studies. For more insight on structure-activity relationships, variou

<i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>) is an opportunistic human pathogen that forms biofilms and produces virulence factors <i>via</i> quorum sensing (QS). Blocking the QS system in <i>P. aeruginosa</i> is an excellent strategy to reduce biofilm formation and the production of virulence factors. RhlR plays an essential role in the QS system of <i>P. aeruginosa</i>. We synthesized 55 analogues based on the chemical structure of 4-gingerol and evaluated their RhlR inhibitory activit

Thymic stromal lymphopoietin (TSLP) plays an important role in the differentiation and proliferation of Th2 cells, resulting in eosinophilic inflammation and numerous allergic diseases. Baicalein (1), a major component of Scutellaria baicalensis, was found to be the first small molecule to block TSLP signaling pathways. It inhibited effectively eosinophil infiltration in house dust mite-induced and ovalbumin-challenged mouse models. Structure-activity relationship studies identified compound 11a

One category of boron neutron capture therapy (BNCT) agents that has received extensive attention during recent years is 3-carboranyl thymidine analogues (3CTAs). These molecules are phosphorylated to the corresponding 5'-monophosphates by human thymidine kinase 1 (TK1), an enzyme that is up-regulated in dividing malignant cells. Thus, these phosphorylated molecules are selectively entrapped in tumor cells due to the acquired negative charge. This review will analyze design strategies applied fo

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic gram-negative pathogen that can cause various infections, particularly in patients with compromised host defenses. P. aeruginosa forms biofilms and produces virulence factors through quorum sensing (QS) network, resulting in resistance to antibiotics. RhlI/RhlR, one of key QS systems in P. aeruginosa, is considered an attractive target for inhibiting biofilm formation and attenuating virulence factors. Several recent studies examined sma

Nineteen lipophilic thymidine phosphate-mimicking compounds were designed and synthesized as potential inhibitors of thymidine monophosphate kinase of Bacillus anthracis, a Gram-positive bacterium that causes anthrax. These thymidine analogues were substituted at the 5'-postion with sulfonamide-, amide-, (thio)urea-, or triazole groups, which served as lipophilic surrogates for phosphate. Three of the tested compounds produced inhibition of B. anthracis Sterne growth and/or thymidine monophospha

There are few hybrid positron emission tomography (PET)/fluorescence imaging agents available for brain imaging. For this purpose, BODIPY dye is very attractive because one of its fluorine atoms can be readily exchanged with ¹⁸F, and it can be modified to produce red-shifted fluorescence. In this study, therefore, we synthesized and investigated a ¹⁸F-labeled red-shifted BODIPY dye as a prosthetic group for brain hybrid PET/optical imaging agents and determined the optimal

Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evaluated twelve AKT inhibitors and revealed GDC0068 as a potential agent to ameliorate senescence. Senescence-ameliorating effect was evident from the finding that GDC0068 yielded lysosomal functional rec

<i>Pseudomonas aeruginosa</i> is a ubiquitous gram-negative bacterium capable of forming a biofilm on living and non-living surfaces, which frequently leads to undesirable consequences. We found that lauroyl arginate ethyl (LAE), a synthetic non-oxidizing biocide, inhibited biofilm formation by <i>P. aeruginosa</i> at a sub-growth inhibitory concentration under both static and flow conditions. A global transcriptome analysis was conducted using a gene chip microarray to identify the genes target