PubMed Health⌕ Search

Biomedical subjects

Heekyung Tak

Publications and source records attributed to Heekyung Tak.

3 recordsLinked to original sources

Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2-cycloalkenones.

The antitumor activity of 2-crotonyloxymethyl-2-cyclohexenone (COMC-6) is not the result of the GSH conjugate (GSMC-6) formed inside tumor cells, as the diethyl ester prodrug form of GSMC-6 displays little antitumor activity with B16 melanotic melanoma in vitro (IC(50) > 460 microM) versus COMC-6 (IC(50) 0.041 microM) and its five- and seven-membered ring homologues. Antitumor activity probably results from a reactive intermediate that forms during conjugation of the COMCs with intracellular GSH.

Animals↗

A Stachybotrys chartarum isolate from soybean.

As part of our effort to investigate fungi associated with soybean roots, Stachybotrys chartarum was isolated from soybean root lesions. Since this fungus has not been reported to cause a disease of soybean, the objectives were to identify and characterize this fungus using biological, chemical, and molecular approaches. Fungal morphology was examined using light and environmental scanning electron microscopy. Phialides bearing conidia arose from determinate, macronematous, dark olivaceous conidiophores. The phialides were obovate or ellipsoidal in whorls. Conidia were unicellular, round or ellipsoidal, 5-13 x 4-7 microm, initially hyaline with smooth walls then dark brown to black and rough-walled when mature. Radial growth of the fungus on cornmeal, oatmeal and potato dextrose agar was 38, 47, and 33 mm in diam., respectively, after 10 days at 25 degrees C. Pathogenicity was performed using sorghum grain colonized by S. chartarum placed below sown soybean seeds in a soil: sand (1:1) steam-pasteurized mix. Three weeks after inoculation, root lesions ranged from 7 to 25 mm long. The fungus was reisolated from soybean root lesions and was reidentified as S. chartarum. Biochemical analysis indicated that this soybean isolate produced satratoxins G and H along with roridin L-2, as well as the spircyclic lactones and lactams in rice culture. PCR using a S. chartarum-specific primer StacR3 and IT51 amplified a 198-bp DNA fragment from the total genomic DNA. The DNA sequence of the ITS region was 100% identical to the S. chartarum strain ATCC 9182, one nucleotide mismatch with S. chartarum strain UAMH 7900, and differed from all published sequences of 12 other species of Stachybotrys and 2 species of Memnoniella in GenBank with genetic divergence ranging from 5.26 to 9.98%. This molecular evidence further supports the identification of S. chartarum isolated from soybean root lesions.

Chromatography, High Pressure Liquid↗

N-(2-hydroxypropyl)methacrylamide copolymers of a glutathione (GSH)-activated glyoxalase i inhibitor and DNA alkylating agent: synthesis, reaction kinetics with GSH, and in vitro antitumor activities.

The incorporation of anticancer prodrugs into polyacrylamide conjugates has been shown to improve tumor targeting via the so-called "enhanced permeability and retention" effect. This strategy has now been expanded to include two different classes of glutathione (GSH)-activated antitumor agents prepared by radical polymerization of N-(2-hydroxypropyl)methacrylamide (HPMA) with 2-methacryloyloxy-methyl-2-cyclohexenone (7) and/or with S-(N-4-chlorophenyl-N-hydroxycarbamoyl-thioethyl)methacrylamide (8), followed by treatment with 3-chloroperoxybenzoic acid, to give the HPMA copolymers of 7 and the 8-sulfoxide, respectively. In aqueous-buffered solution at pH 6.5, GSH reacts rapidly with poly-HPMA-8-sulfoxide (k approximately 2.3 mM(-1) min(-1)) to give S-(N-4-chlorophenyl-N-hydroxycarbamoyl)glutathione (1), a tight-binding transition state analogue inhibitor of the antitumor target enzyme glyoxalase I (K(i) = 46 nM), or with poly-HPMA-7 (k approximately 0.02 mM(-1) min(-1)) to give the electrophilic antitumor agent 3-glutathio-2-methylenecyclohexenone (4). Indeed, B16 melanotic melanoma in culture is inhibited by poly-HPMA-8-sulfoxide and by poly-HPMA-7 with IC(50) values of 168 +/- 8 and 284 +/- 5 microM, respectively. These values are significantly greater than those of the unpolymerized prodrugs suggesting that the cytotoxicity of the polymer prodrugs might be limited by slow cellular uptake via pinocytosis. This prodrug strategy should be applicable to a range of different GSH-based antitumor agents.

Acrylamides↗