Letters in Drug Design & Discovery - Volume 10, Issue 9, 2013

We have identified SRT2104 (4) as the first direct synthetic SIRT1 activator clinical candidate. The compound was derived from the optimization of a previously described imidazo[1,2-b]thiazole scaffold. SRT2104 was selected as a development candidate based on a combination of biochemical activity and pharmacokinetic profile. The in vivo characteristics of SRT2104 were superior to those of analogues with similar activation p Read More

Synthesis, characterization and investigation of antibacterial and antifungal activities of thirteen novel 6- hydroxybenzofuran-3(2H)-one based 2,4-disubstituted 1,3-thiazoles are presented. Their structures were determined using NMR, FAB MS and HRMS analyses. The results of microbiological screening reveal that three derivatives containing fluorine, bromine and hydrogen substituents at the phenyl ring are the most active an Read More

Carbonic anhydrase (CA) IX is considered as a potential target for cancer therapy. In order to identify new scaffolds compounds and use them for designing novel CA IX inhibitors, herein 3D pharmacophore hypotheses had been established. Alignment and Scoring Engine (PHASE) software has been used to develop ligand-based pharmacophore model using a large set of 36 different aromatic/ heterocyclic sulfamates carbonic a Read More

Hyperlipidemia is a common cardiovascular disease characterized by elevated lipid level in association with disordered lipoproteins metabolism. Atorvastatin, an HMG-CoA reductase inhibitor, has been developed as an antihyperlipidaemic agent and proved to exhibit antioxidant activity against lipid peroxidation. The two hydroxyl metabolites of atorvastatin, Ortho-hydroxy-atorvastatin and para-hydroxy-atorvastatin, are Read More

Three-dimensional quantitative structure activity relationship (3D-QSAR) studies were performed for a series of ribonuclease H inhibitors using comparative molecular field analysis (CoMFA), comparative molecular similarity indices analysis (CoMSIA) and docking studies. A large set of 33 different aromatic/ heterocyclic N-hydroxy 1,8- naphthyridine 2-one analogs as Ribonuclease H inhibitors wher chosen for the present st Read More

S1P1 is an important target from GPCR family, whose crystal structure was released recently. Here, for the first time, we perform the 3D-QSAR analyses on a series of pyrazole oxadiazole derivatives, which are potent S1P1 agonists, by CoMFA and CoMSIA. We use two basic common cores, oxadiazole and pyrazole-oxadiazole, to align all compounds to establish the models of COMFA and COMSIA. The best CoMFA model by ap Read More

Cyclodextrins are capable to configure as a host-guest complexes in the company of hydrophobic molecules due to their emblematic nature imparted by their structural arrangement. The aim of present study is based on the application of in-silico tool for the selection of NSAID to develop novel drug delivery systems using β-Cyclodextrin. An understanding of the structural and binding properties of cyclodextrin with NSAIDs Read More

Metal complexes of 8-aminoquinoline (8AQ) derivatives were reported. This study presents a series of synthesized transition metal complexes of mixed ligands 8AQ-5-iodouracils (1-3) and 8AQ-5-nitrouracil (4-6) which have been investigated for their antioxidative and cytotoxic activities, as well as, powder X-ray diffraction patterns. Ni complex of 8AQ-5-nitrouracil (6) exerted significant cytotoxicity against MOLT-3 cell and su Read More

The 2-amino-6-trifluoromethyl-3H-pyrimidin-4-one 1 was propargylated to give two regioisomers 2, 3 in definite proportions. Both regioisomers 2 and 3 were independently reacted with alkyl, aryl or cycloalkyl substituted azides under Sharpless conditions and were obtained exclusively 1,4–disubstituted triazole tagged trifluoromethyl substituted pyrimidine derivatives 4 and 5 respectively. All the final products were evaluated Read More

Three platinum (II) complexes (6-8) with phthalate as the leaving group were synthesized and characterized by FTIR, 1H NMR, 13C NMR, mass spectrometry and elemental analysis. In-vitro cytotoxicity of all three complexes was evaluated using COLO 205 (human colon cancer cell line) against the parent drug “oxaliplatin”. The compound 4-amino-(transcyclohexane- 1,2-diamine) platinum(II) (8) showed potent cytotoxicit Read More

A series of novel β-carboline derivatives was synthesized and evaluated for their cytotoxic activities in vitro against two human tumor cell lines. Most of the compounds showed moderate to potent cytotoxic activities against the tested cell lines, in which compound 12l exhibited the most potent antiproliferative activities against KB cell line (IC50 = 4.58 μM). Preliminary mechanism research on compound 12l indicated that Read More

A set of new polyoxo 2-benzyl-2,3-dihydrobenzofurans and their related compounds, including 2- benzylbenzofuran-3(2H)-ones and 2-benzylbenzofurans, were designed and synthesized. Their antiproliferative activities were evaluated against human gastric cancer (SGC-7901), human fibrosarcoma (HT-1080) and human oral epidermoid carcinoma (KB) cell lines in vitro. Preliminary results showed that some poly Read More

Previous studies demonstrated that hydantoin ibuprofen conjugates had effective anti-inflammatory and antitussive activities. In this study, we evaluated their analgesic and gastric ulcerogenic activities. Our results showed that these compounds retained analgesic activity from ibuprofen, more important, could suppress gastric ulceration. Furthermore, by analyzing the metabolites of the compounds in rat plasma using LC- Read More

A series of dihydropyridine analogous was synthesized and evaluated for anticonvulsant activity using PTZ animal model. The main strategies are introducing a non-classical dihydropyridine like structure as anti-seizure agent. Some compounds showed significant anticonvulsant activity in comparison with the control group.

A novel series of substituted thieno[3,2-d]pyrimidin-4(3H)ones 7-22 has been synthesized and evaluated for in vivo antihyperlipidemic activity using Triton WR 1339. Out of the 16 compounds synthesized and tested, 8 compounds have shown significant effect on total lipid profile. These compounds are several times more potent than gemfibrozil, the standard drug used for comparison. The superior activity of compounds Read More