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Quantitative Structure-Activity Relationship (QSAR) models are used increasingly to screen chemical databases and/or virtual chemical libraries for potentially bioactive molecules. These developments emphasize the importance of rigorous model validation to ensure that the models have acceptable predictive power. Using k nearest neighbors (kNN) variable(More)
A series of novel podophyllotoxin derivatives containing structural modifications at C-4 (7-14), C-4' (16-17), and the methylenedioxy A-ring (23-28) was synthesized and tested for inhibition of HIV replication. Four of these compounds (25-28) were previously reported to show EC(50) values of <0.001 microg/mL and therapeutic index (TI) values >120. Three of(More)
The natural diterpenoid andrographolide (1) exhibits various biological activities. Seventeen derivatives of 1 were prepared via esterification and etherification of 14-dehydroxy-11,12-didehydroandrographolide (2). Most derivatives demonstrated significant inhibition against tumor cell growth. The most active compounds, 3b and 3c, had GI50 values of(More)
A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20(More)
As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-phenyl group displayed the highest in(More)
We have applied a variable selection k nearest neighbor quantitative structure-activity relationship (kNN QSAR) method to develop predictive QSAR models for 157 epipodophyllotoxins synthesized previously in our ongoing effort to develop potential anticancer agents. QSAR models were generated using multiple topological descriptors of chemical structures,(More)
Protein tyrosine phosphatase 1B (PTP1B) is a promising therapeutic target for type 2 diabetes. Herein, we report the evolution of a previously identified 3-phenylpropanoic acid-based PTP1B inhibitor to an orally active lead compound. A series of 3-phenylpropanoic acid-based PTP1B inhibitors were synthesized, and three of them,(More)
Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally,(More)
Fifteen new diarylheptanoids were synthesized and evaluated for antagonistic activity against androgen receptor (AR)-mediated reporter gene transcription using DU145, PC-3, and LNCaP prostate cancer cell lines. Most compounds showed activity in a 5alpha-dihydrotestosterone (DHT)-induced reporter gene expression assay in DU145 cells transfected with(More)
Three C4'-acyl derivatives (5-7) of GL-331 (4) were synthesized and evaluated for cytotoxic and DNA topoisomerase II (topo II) inhibitory activity. All three compounds were cytotoxic against KB and KB-7d cells. Compounds 5 and 7, but not 6, were potent inhibitors of the DNA topoisomerase II in vitro and this relative activity ranking was maintained for(More)