Letters in Drug Design & Discovery - Volume 11, Issue 3, 2014

Chagas disease is an infection caused by the intracellular protozoan Trypanosoma cruzi. It is estimated that more than 10 million people are infected, with 25 million living in areas at risk. The only drugs currently used in the therapy against this disease are nifurtimox and benznidazole; both, however, are only effective in the acute phase and also highly toxic. Therefore, the development of new drug candidates against t Read More

In the course of our ongoing program dedicated to the synthesis of anti-proliferative compounds, we prepared new troglitazone derivatives bearing a biphenyle moiety. The chromane heterocycle was further replaced by imidazole and triazole derivatives. Many compounds exhibited fair to high activity towards various cancer cell lines. Among them, compound 17b reduced cell viability leading to only 22-34% viable cells in four c Read More

A QSAR study is reported to predict the binding affinity of a set of 81 modulators for both of human estrogen receptor α and β (ERα and ERβ). In this study, the derived QSAR models were built by forward stepwise multilinear regression (MLR) and nonlinear radial basis function neural networks (RBFNN), respectively. The statistical characteristics of the external test set provided by multiple linear model (R2=0.814, F=61.277, RM Read More

Semi-synthetic C-10 alkyl thio analogues of the cytotoxic natural alkaloid colchicine have been found to exhibit cytotoxicity towards tumour cell lines at levels comparable to that of the natural product. An efficient synthesis of 10-alkyl thiocolchicines in mild conditions is proposed and the products are studied by 1H and 13C NMR, FT-IR, MS-EI methods and elementary analysis. The crystal structure of 10-ethylthiocolchicine is charact Read More

A series of 4,5-disubstituted-1,2,4-triazole-3-thione derivatives (4a-e) and their N-Mannich bases (5a-e), together with a S-benzyl derivative (6), were synthesized and evaluated as antimycobacterial and antiproliferative agents. The structures of the compounds were established by IR, 1H-NMR, 13C-NMR and 2D-NMR spectroscopic methods and microanalysis. 4 and 5 were screened for in vitro antimycobacterial activity aga Read More

The paper presents a novel synthesis of AZT modified derivatives via click chemistry. Firstly, the reaction of 2,4-dihydroxyacetophenone (1) with propargyl bromide in acetone gave intermediates 2 in 75% yield. Next, new chalcones 3a-g were obtained in 55-65% yields through the Claisen-Schmidt reaction of 2 with different aromatic aldehydes. These chalcones were then oxidatively cyclized in DMSO in the presence of I2 t Read More

A series of 1,3,4-oxadiazole-2-thiol incorporating fatty acid moieties was synthesized. The chemical structure of the synthesized compounds was established by their spectral data, elemental analysis, and their chemical behavior. Their thioglycosides derivatives and the analogous 1,2,4-triazole were also prepared. The in vitro cytotoxicty of the synthesized compounds was screened against two cell lines; breast cell line MCF-7, an Read More

In the present study, 3D-QSAR analysis was performed on a set of 37 TGF-β inhibitors utilizing pharmacophore based alignment to uncover the essential structural and steric features of these newly discovered b-annulated 1,4- dihydropyridine (1,4-DHP) molecules to get better antagonism of the TGF-β receptor. The best 3D-QSAR model identified with PLS factor 4 that had the highest values of external predictability paramete Read More

Cholinesterases (ChEs) play a vital role in the regulation of cholinergic transmission. The inhibition of ChEs is considered to be involved in increasing acetylcholine level in the brain and thus has been implicated in the treatment of Alzheimer’s disease. We have designed and synthesized a series of novel indole derivatives and screened them for inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of the t Read More

Transthyretin (TTR) is a homotetrameric plasma protein that has been associated with numerous human amyloid diseases. Although Tafamidis has recently been approved for the treatment of TTR familial amyloid polyneuropathy (FAP), there is still a need persists for drugs that are more effective in the treatment of TTR amyloidosis diseases. Therefore, we propose ligand-based and structure-based pharmacophore model Read More

Here we employed simple chemistry for the synthesis of a new potent series of benzo[b]thiophene containing 2-carbonylchlorides (1), 2-isopropyl carboxamides (2), 2-(piperidin-1-yl)-methanones (3) by nucleophilic chloro cyclocondensation of substituted-cinnamic acids with thionyl chloride to afford benzo[b]thiophene nucleus. The constitution of the products has been delineated by elemental analysis and spectral analyses. Th Read More

Nineteen N'-(benzylidene)-2-[(pyrimidin-2-yl)thio]acetohydrazides were obtained via the nucleophilic addition- elimination reaction of 2-[(pyrimidin-2-yl)thio)]acetohydrazide with aromatic aldehydes. The synthesized compounds were tested in vitro against various bacteria by microdilution. Among these compounds, N'-(3- hydroxybenzylidene)-2-[(pyrimidin-2-yl)thio]acetohydrazide (3l) was found to be the most potent deriva Read More

The interaction of hepcidin (HEPC) and ferroportin (FPN) is an essential event in iron homeostasis. HEPC binds to FPN, and subsequently degrades it through phosphorylation and ubiquitination. Present work described a computational study to identify interfacial residues involved in FPN–HEPC interactions. We have predicted three-dimensional structure of human FPN using homology modeling followed by docking analysis and Read More

N-[(7-pyridin-4-yl-2, 3-dihydro-benzofuran-2-yl) methyl]-(4-methyl-1, 2, 3-thiadiazole-5-yl)-Formamide (1) was synthesized and its immunosuppressive activity was evaluated. The results showed it had highly immunosuppressive activity and can be studied as lead compound in the development of immunosuppressant agent.

A new series of (1R,5R)-(-)-3-arylidenenopinones was synthesized from (1S,5S)-(-)-β-pinene which was a natural chemical from pine tree, and their ultraviolet absorption characteristics were investigated. (1R,5S)-(+)-nopinone was obtained from (1S,5S)-(-)-β-pinene by selective oxidation, and then it was reacted with benzaldehyde, phydroxybenzaldehyde, vanillin, o-vanillin, p-chlorobenzaldehyde, and p-methylaldehyde in the p Read More