Letters in Drug Design & Discovery - Volume 13, Issue 1, 2016

Serine proteases are involved in the blood coagulation cascade- composed of intrinsic, extrinsic, and common pathways affecting coagulation responses. Among the three pathways of the blood coagulation cascade involving serine proteases, this review focuses on serine protease inhibitors of the understudied extrinsic pathway, which is responsible for bleeding and bleeding complications targeting the (activated fa Read More

Out of many idiopathic causes, mutation in some genes is linked to Parkinson’s disease (PD). Recent studies showed pathogenic mutation in the kinase domain of the leucine rich repeat kinase (LRRK2) leads to PD, and increasingly gaining attention as a promising therapeutic target. Some of the reported LRRK2 inhibitors have shown undesirable drug properties, primarily the inability to cross the blood-brain barrier. The energ Read More

In this study, a nonlinear quantitative structure-activity relationship model for the prediction of the IC50 of trisubstituted thiazoles as Cdc7 kinase inhibitors was developed by the gene expression programming (GEP). This model is based on five descriptors which were selected from the descriptors’ pool by heuristic method (HM). GEP rendered a good correlation between the experimental and predicted log (IC50) values Read More

A group of class I selective HDAC inhibitors were derived previously, with inhibitory preference of HDAC1 and HDAC3 over HDAC2. Molecular docking and molecular dynamic simulation approaches were performed to elucidate the structural basis of inhibitor’s selectivity between HDAC2 and HDAC3. Superimposition of the rigid docked structures showed that residues in the active sites of both receptors are identical, and t Read More

Among anticancer DNA-intercalating agents, medicinally important 1,8-naphthalimide derivatives represent an important class of bioleads possessed substantial cytotoxic activity toward a variety of murine and human cancercells. Amonafide, as the representative of this family, plays an important role due to its potent antitumor properties. Amonafide is a topoisomerase II (Topo II) inhibitor and DNA intercalator that induc Read More

A series of 6,7-disubstituted-3-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}quinazoline- 2,4(1H,3H)-dione derivatives (7-34) were synthesized and their structures were elucidated on the basis of analytical and spectral (UV, IR, 1H-NMR, 13C-NMR and MS) data. These synthesized compounds were evaluated for their in vitro cytotoxicities against a panel of three human cancer cell lines. According to the cytotoxicity screening r Read More

In the present study, novel derivatives of 7H-benzo[h]chromeno[2,3-d]pyrimidine were prepared from 4H-benzo[h]chromene-3-carbonitrile and ethyl 4H-benzo[h]chromene-3-carboxylate derivatives and were evaluated as potential cytotoxic agents. The structures of the synthesized compounds were established on the basis of spectral data, IR, 1H NMR, 13C NMR and MS data. The invitro antitumor activity of the synt Read More

Some new quinoline derivatives were designed and synthesized to evaluate their biological activities as aromatase inhibitors and anti-breast cancer agents. Cytotoxicity of quinolines 8a-g against human breast cancer MCF-7 and T47D cell lines were evaluated. All the compounds 8a-g were more cytotoxic against MCF-7 cells in comparison with those of T47D which express aromatase mRNA less than MCF-7 cells. Their effects on A Read More

A series of aminopeptidase N (APN) inhibitors were designed and synthesized. Enzyme inhibitory, docking and antiproliferative studies were performed to evaluate the derived molecules. Molecule D15, with IC50 values of 10.9 μM, showed the best performance in the APN enzymatic inhibition assay. The binding pattern of molecule D9 and D15 in the active site of APN was predicted by docking studies. Hydrophobic an Read More

This work describes the synthesis and biological properties of a series of 2- and 4- pyridinylimines and pyridinylhydrazones. All compounds were evaluated in vitro against two species of Leishmania. The antioxidant activity and the toxic effect against murine peritoneal macrophages of the compounds were also performed. The synthesized compounds showed significant antileishmanial and antioxidant activities. For the antil Read More