Letters in Drug Design & Discovery - Volume 11, Issue 7, 2014

The anticancer drug candidate 1,3-di(p-methoxybenzyl)-4,5-di(p-isopropylphenyl)-imidazol-2-ylidene copper( I) bromide (WBC4) was tested on the NCI 60 cancer cell panel in vitro. WBC4 showed very good activity against a wide range of human cancer cell lines inclusive renal cell cancer with an average GI50 value of 288 nM. This encouraged maximum tolerable dose (MTD) experiments in mice, where a MTD value of 10 mg/k Read More

New pyrazole-based thiazolyl hydrazone derivatives were obtained via the ring closure reaction of 3,5- dimethyl-1H-1-phenylpyrazole-4-carboxaldehyde thiosemicarbazone with 2-bromoacetophenone derivatives. The compounds were investigated for their cytotoxic effects on A549 and NIH3T3 cell lines. Among these compounds, compound 2i bearing a trifluoromethyl substituent can be identified as the most promis Read More

This study describes the synthesis of four 2,4,5-triarylimidazole derivatives and their anticancer activities. The target compounds were prepared from the reaction of benzaldehyde and benzoin derivatives in presence of ammonium acetate and ammonium vanadate. All the synthesized compounds were screened for anticancer activities against T47D and MDA-MB231 cell lines using the MTT assay. However, our obtained Read More

The structure of the compound depends on connectivity of its constituent atoms. Topological descriptors based on connectivity can reveal the role of structural and substructural information of molecules in estimating biological activity. The present study involves conceptualization of six detour cum distance matrix based topological descriptors (TDs) termed as relative distance sum descriptors and relative distance product desc Read More

β-secretase (BACE1) inhibition has emerged as a most promising target for the treatment of Alzheimer’s disease. In the present study an in silico approach has been successfully utilized for the development of diverse classification models for the prediction of BACE1 inhibitory activity using a dataset consisting of 42 differently substituted aminohydantoin analogues. Classification tree (CT), moving average analysis (MAA) and r Read More

A series of novel carvacrol and thymol derivatives containing 5-phenyl-2-furan were synthesized. The antitumor tests showed that the title compounds exhibited promising activity against Bel-7402 and KB. The fungicidal tests showed that most of the title compounds had a considerable effect on the selected fungi. Generally the bioactivity of the carvacrol and its derivatives were better than that of the thymol and its deri Read More

Dipeptidyl peptidase-IV (DPP-IV) is well known to be an attractive therapeutic target to treat type II diabetes. The aim of this work is to determine the residues which make great contributions to inhibitor binding by comparing the interactions between different inhibitors and residues in DPP-IV. To achieve this, two DPP-IV/inhibitor complexes were studied by molecular dynamics simulations. Hydrogen bond and interaction energy Read More

MEK proteins play a critical role in tumor proliferation, differentiation, and survival. Hence MEK1 inhibitors are of particular importance in the treatment of related diseases. The present study describes pharmacophore-based 3DQSAR model generation based on 82 known inhibitors of MEK1 allosteric binding cavity. The best pharmacophore model developed consisted of four features, namely AHHR. The model was use Read More

Inherited defect of the gene ATP7B causes malexcretion of copper in the bile and leads to several complications that need treatment to deplete it from organs. Current therapy of Wilson disease, D-penicillamine has very serious side effects and drug with optimum therapeutic effects and minimum side effects is of importance. In the present study ciprofloxacin was conjugated with an anionic globular dendrimer to lower th Read More

Herein, we have investigated novel pyrimidine nucleosides bearing a 4’-carboxyl functionality (6-10, 13 and 15) as anti-HCV agents. In this new class of compounds, 7, 9, 10 and 15 demonstrated in vitro anti-HCV activity similar to or better than a known anti-HCV drug, ribavirin. In this work, we also, surprisingly, identified a 3’-sulfoxide analog of 3’-thiacytidine (16), obtained as a side product during the synthesis of 15, as a po Read More

Meloxicam is a non-steroidal anti-inflammatory drug used in the treatment of rheumatoid arthritis, osteoarthritis and other inflammatory diseases. However, its prolonged use is associated to several side effects like gastrointestinal perforations, ulcerations and bleeding, probably due its low aqueous solubility and wettability after oral administration. These side effects can reduce patient compliance and discourage physician f Read More

In the present article, the antimicrobial properties of ethyl 4-amino-2-mercapto-6-arylpyrimidine-5-carboxylate (2a-h) and ethyl 2-(2,4-dinitrophenylthio)-4-amino-6-arylpyrimidine-5-carboxylate (3a-h) were studied. Biginelli typed three component reaction between an aldehyde, ethyl cyanoacetate and a thiourea constituent which gives a rapid facile 3,4-dihydropyrimidine ring (1a-h), which on aromatization using Read More

The high toxicity and the growing resistance are the major drawbacks of available antileishmanials. Our previous in vitro studies have identified oxabicyclo[3.3.1]nonanones as antileishmanial agents that act on the redox enzymes of the parasite. In the current study, antileishmanial activity of 4-(4,4,8-trimethyl-7-oxo-3-oxabicyclo[3.3.1]non-2-yl)- benzoic acid methyl ester (PS 203) the most potent oxabicyclo[3.3.1]nonanone ide Read More

A series of 4-methyl-N-(5-substituted-1, 3,4-thiadiazol-2-yl)-1,2,3-thiadiazole-5-carboxamide 6a~6j. The chemical structures were confirmed by 1H NMR, FTIR, MS, and elemental analysis. All the compounds were investigated for antifungal activity. The antifungal activity results indicated that compound 6a exhibited good activities against C. arachidicola. It can be compared with the commercial drug. The compounds 6e, 6f, 6i, Read More

The ABHD6 and ABHD12 are newly discovered post-genomic proteins which act as 2-arachidonoylglycerol hydrolases. Their physiological importance is largely unknown, however high expression of ABHD6 is attributed to some forms of cancer. Only a few inhibitors are known for ABHD6 and ABHD12 enzymes. In search for novel inhibitors of ABHD6 and ABHD12 hydrolases we tested a set of heterocyclic compoun Read More