Letters in Drug Design & Discovery - Volume 5, Issue 8, 2008

Advanced glycation end product (AGE) and receptor (RAGE) axis play a central role in the pathogenesis of diabetic vascular complications. Since peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists have been reported to reduce RAGE gene expression and subsequently suppress the downstream signalings in human umbilical vein endothelial cells (HUVECs), we examined here whether telmisartan, a unique angiotensin Read More

We report herein the synthesis of a series of eight novel compounds based on the coupling of 6-mercaptopurine (4), 2-mercaptopyrimidine (5), 4-mercaptopyridine (6) and 2-mercaptobenzimidazole (7) with 6-deoxy-6-iodo-1,2:3,4-di- O-isopropylidene-γ-D-psicofuranose and subsequent deprotection. The compounds were evaluated in vitro for activity against Leishmania amazonensis and L. chagasi promastigotes and for Read More

The anticancer activities of six imido-substituted 2-chloro-1,4-naphthoquinone derivatives on one androgendependent, LNCaP, and two androgen-independent, PC3 and DU145, human prostate cancer cell lines are reported. The open chain imides (2-4) showed more potency in all three cell lines. In addition the microwave-assisted synthesis of five of these compounds is reported.

The para-methoxybenzyl-substituted titanocene oxalate (Oxali-Titanocene Y) was tested in vitro in an antiangiogenesis assay against human umbilical vein endothelial cells, HUVEC, delivering an IC50 value of 14 μM and in a cytotoxicity assay against the human renal cancer cells, CAKI-1, which demonstrated an IC50 value greater than 100 μM. Then Oxali-Titanocene Y was given at 30 mg/kg/d, which is the maximum toler Read More

A consensus QSAR combining traditional 2D-QSAR with CoMFA and CoMSIA was developed for N, N'- bis substituted guanidines reported with NMDA receptor ion channel blocker activity. Two new statistics r2wμp (leverage weighted mean r2pred) and r2μp (mean r2pred) were defined. A slight improvement in predictive ability was observed for all the combinations while using r2wμp (0.630, 0.691, 0.672) rather than r2μp (0.622, Read More

A novel series of dual PPARα/γ agonists was designed through the modification of our previously described family of 8-HETE analogs. The combination of the structural elements of this family and of the classical PPAR ligands produced compounds with a quinoxaline core and two sides chains. Structure-activity relationship studies have been carried out on the new series and compounds belonging to this new family have Read More

Molecular modeling of flavonoid/β-cyclodextrin complexes was used for rationalization of 1H-NMR data. We describe an algorithm that allows exact definition of the starting host-guest orientation. We used this algorithm to build complexes of two flavonoids, quercetin and myricetin. Subsequent molecular dynamics simulations yielded structures consistent with NMR data for the flavonoid position in the β-cyclodextrin cavity.