Letters in Drug Design & Discovery - Volume 8, Issue 1, 2011

Molecular modelling studies of complexes of 2-phenylamino-6-oxopurines and HSV1 thymidine kinases (TK) revealed two distinct modes of binding. The “acyclovir mode” was occupied by 9R (9-substituted) compounds, and was identical to that revealed by crystal structures of acyclovir and 2-phenylamino-9-(4-hydroxybutyl)-6-oxopurine (HBPG) bound to HSV1 TK. The “base mode” was occupied by 9H compounds such as 2-[3- Read More

Src has been recognized as an important therapeutic target for the treatment of cancer. A novel series of triazole- based Src inhibitors were synthesized and evaluated for their anti-proliferative activities in vitro against human lung cancer A549 cells with Bosutinib as reference compound, most of the compounds showed more potent activity than Bosutinib. Compounds 6 and 8 were further subjected to pharmacokinetic per Read More

A QSAR analysis of 25 isosteviol derivatives was carried out to interpret the relationship between structural properties and α-glucosidase inhibitory activity. The selected significant models have good predictive ability, which was validated by LOO cross validation techniques (Q2>0.6) and which gives significant Cook's distances (<1) and other statistical parameters. The selected significant models suggest that the nitrogen count Read More

We report the tentative initial results of our on-going search for potent inhibitors of estrone sulfatase (ES), here we report a series of alkyl 6-aminosulfonyl naphthanoate-based compounds as potential inhibitors. The results suggest that the compounds are weak inhibitors in comparison to the standard compound used within the current study.

The FLAP inhibitory activity of 2,2-bisaryl-bicycloheptane derivatives has been quantitatively analyzed in terms of Dragon descriptors. The derived QSAR models have provided rationales to explain the FLAP inhibitory activity of 2,2-bisaryl-bicycloheptane derivatives. The presence of quinolinylmethoxy substituent at R2-position in a molecular structure is a crucial feature for the FLAP inhibitory activity. The occurrence Read More

Various significant anti-HCV and cytotoxic sesquiterpene lactones (SLs) have been characterized. In this work, the chemometric tool Principal Component Analysis (PCA) was applied to two sets of SLs and the variance of the biological activity was explored. The first principal component accounts for as much of the variability in the data as possible, and each succeeding component accounts for as much of the remaining Read More

The novel phosphorylated derivatives of Lamivudine (5a-5l) as potential anti colon cancer agents are synthesized. These title compounds are designed based on the basic pyrimidine derivative lamivudine as a starting compound and reacted with various phosphorodichloridates followed by the introduction of bioactive groups at the phosphorus. Their structures were characterized by IR, 1H, 13C, 31P NMR and mass spectral Read More

Mutant selection window (MSW) is the antimicrobial concentration ranging from the minimum inhibitory concentration (MIC) to the mutant prevention concentration (MPC). Placing antibiotic concentration in the MSW is expected to selectively enrich mutant subpopulations while placing the concentration above the window is expected to restrict the selective enrichment of resistant bacteria. Even though there is a rise of Read More

This study was designed to assess the effect of honey supplementation and sugar-based hypercaloric regimen on weight gain and blood pressure (BP) in Wistar rats. Animals were fed for 8 weeks with standard diet (S-free) or a hypercaloric diet (standard chow and 30% sugar in drinking water), (SF), or standard chow supplemented with fat and honey and 10% sugar in drinking water (HF). Overall weight gain and body fat Read More

TRPV1 is a ligand-gated non-selective cation channel that is considered to be an important pain integrator. Capsaicin, the prototypical TRPV1 agonist, has a clear therapeutic potential. In this letter, for lowering its pungency, a series of nitric oxide-releasing derivatives of capsaicin were designed and synthesized, including 10 compounds which were the direct combination of capsaicin and dihydro capsaicin with various ni Read More

A series of 1,3-thiazolidin-4-one derivatives were prepared by the reaction of respective aromatic amine, aromatic aldehyde and thioglycolic acid in dry benzene/toluene. The newly synthesized compounds were characterized on the basis of elemental analysis, IR, 1HNMR and mass spectra. The newly synthesized final compounds were evaluated for their in-vitro antibacterial, antifungal and anti-viral activities. Preliminary results i Read More

Methylnaltrexone (MNTX) is a peripherally-acting opioid receptor antagonist. Since it has restricted access to the blood-brain barrier, MNTX has the ability to decrease opioid-induced constipation without affecting the analgesic effects of opioid pain medications. MNTX has a limited gastrointestinal absorption and currently, only subcutaneous MNTX is clinically available to help restore bowel function in patients with la Read More

Drug discovery in the field of oncology has been advanced mainly through the targeting of receptor tyrosine kinases. Both antibodies and small molecule inhibitors have been found to have successful applications in blocking the proliferative functions of these cell surface receptors. Based on these early successes, additional kinases within the cytoplasm have been found to promote cancer and, as such, have been recognized Read More