Potent inhibition of tributyltin (TBT) and triphenyltin (TPT) against multiple UDP-glucuronosyltransferases (UGT): A new potential mechanism underlying endocrine disrupting actions.

Organotin compounds (OTs) act as potent endocrine disruptors that are often found in polluted food and water. UDP-glucuronosyltransferases (UGTs) are responsible for termination of multiple endogenous hormones. This study was conducted to investigate the inhibitory effects of two tri-submitted OTs tributyltin (TBT) and triphenyltin (TPT), against activities of UGTs. It is revealed that TBT and TPT act as two potent inhibitors for multiple UGTs. UGT1A8 and -2B15 were coinhibited by the two OTs. UGT1A1 and -1A10 were inhibited by TPT, whereas UGT 2B4 and -2B7 were inhibited by TBT. Kinetic analyses further indicated that TBT and TPT are two competitive nanomolar inhibitors of UGT2B15, with Ki values of 0.45 and 0.46 µM, respectively. Ki values for the other UGTs are determined to be a few micromolars. In addition, the two OTs displayed effective inhibition against UGT2B15 in catalyzing dihydrotestosterone glucuronidation, with IC50 values both in nano-molar range. TPT can additionally inhibit activities of UGT1A1 and -1A10 in estradiol-3-O-glucuronidation, with IC50 values of a few micro-molars. These results indicated that the two OTs can extensively interfere with glucuronidation of endogenous hormones, which may act as a new potential mechanism resulting in endocrine disrupting actions.

Effects of single and double bonds in linkers on colorimetric and fluorescent sensing properties of polyving akohol grafting rhodamine hydrazides.

Two rhodamine derivatives, N-mono-maleic acid amide-N'-rhodamine B hydrazide (MRBH) and N-mono-succinic acid amide-N'-rhodamine 6G hydrazide (SR6GH), were synthesized by amidation with maleic anhydride (MAH), succinic anhydride (SAH) and rhodamine B hydrazide, rhodamine 6G hydrazide, which were identified by FTIR, (1)H NMR and elemental analysis. Two water-soluble fluorescent materials (PVA-MRBH and PVA-SR6GH) were prepared via esterification reaction with N-mono-maleic acyl chloride amide-N'-rhodamine B hydrazide (MRBHCl) or N-mono-maleic acyl chloride amide-N'-rhodamine 6G hydrazide (SR6GHCl) and poly(vinyl alcohol) (PVA) in DMSO solution. The sensing behaviors of PVA-MRBH and PVA-SR6GH were explored by recording the fluorescence spectra in completely aqueous solution. Upon the addition of Cu(2+) and Fe(3+) ions to the aqueous solution of PVA-MRBH, visual color change from rose pink to amaranth and orange for Cu(2+) and Fe(3+) ions, respectively, and fluorescence quenching were observed. Titration of Cu(2+), Fe(3+), Cr(3+) or Hg(2+) into the aqueous solution of PVA-SR6GH, although they induced fluorescence enhancement, only Fe(3+) made the color changing from colorless to yellow. Moreover, other metal ions did not induce obvious changes to color and the fluorescence spectra.

Synthesis and biological evaluation of novel 1,6-diaryl pyridin-2(1H)-one analogs.

A series of 1,6-diaryl pyridin-2(1H)-one analogs were designed and synthesized via consecutive Chan-Lam coupling and Suzuki coupling. These novel compounds were evaluated for their antiproliferative activity against two tumor cell lines (SKOV-3 and HepG2). Compounds 1b, 1c, 1e and 1f displayed comparable in vitro cytotoxicity with taxol, while their in vivo antitumor activity was less effective than taxol. In addition, cell cycle assay indicated that these 1,6-diaryl pyridin-2(1H)-one compounds induced cell cycle arrest in the G1/M phase in the HepG2 cell line.

Synthesis and in vitro cytotoxic evaluation of novel N-(3,4,5-trimethoxyphenyl)pyridin-2(1H)-one derivatives.

A series of novel [Formula: see text]-(3,4,5-trimethoxyphenyl)pyridin-2([Formula: see text])-one derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity against human colon cancer cells HCT-116. The key steps involved consecutive Chan-Lam- and Buchwald-Hartwig couplings. Most of these C-6 substituted pyridone derivatives showed moderate antiproliferative activity. The preliminary SAR indicated that the conformationally restricted pyridones exhibited more potent cytotoxicity than the flexible counterparts. In addition, cell cycle analysis of the selected compounds 4b and e showed a G2/M arrest, suggesting a possible antitubulin mechanism for these novel pyridone derivatives.