Letters in Drug Design & Discovery - Volume 13, Issue 9, 2016

A quantitative structure-activity relationship analysis has been applied to a series of 97 imidazopyridine analogous Spleen tyrosine kinase (Syk) inhibitors, the enzyme responsible for the signal transduction of classic immunoreceptors. The deregulation of Syk is associated with several pathologies, among which uncontrolled tumor cell growth stands out. The most advanced Syk inhibitor, fostamatinib, has proven efficien Read More

Cancer is the second largest cause of deaths across the globe. The current treatments available for cancer include surgical removal of the infected tissue, radiotherapy, chemotherapy and combinatorial therapeutic approach. Most of the commercially available anti-cancer drugs and their unique modes of action are decoded by the cancer cells, making them less effective. Hence, there is an increasing demand for newer cl Read More

Benign prostatic hyperplasia is non-malignant enlargement of prostate gland which results in severe lower urinary tract symptoms and affects the quality of life of patients. 5α-Reductase inhibitors play a crucial role in the management of benign prostatic diseases with low toxicity and have been a major thrust area for its application in prostate cancers with limited success. In continuation of our program to develop novel 5α- Read More

Interleukin-1 receptor-associated kinase 4 (IRAK-4) plays a pivotal role in signaling cascades associated with the immune and inflammatory diseases. Regulation of IRAK-4 is an attractive approach to treating related diseases. Herein, ligand-based pharmacophore model and atom-based 3D-QSAR studies have been carried out on 92 known ATP competitive inhibitors to IRAK-4. Fourpoint pharmacophore hypotheses with on Read More

Selected synthesized biologically active fluorinated diethyl-2-(benzylthio)-2,3-dihydro- 1H-imidazole-4,5-dicarboxylate derivatives exhibited promising anti-platelet aggregation activity against thrombin. With a view to understanding their structural features, some common electronic structural characteristics, including polarizability (α), ΔELUMO-HOMO, chemical hardness (η) and softness (S) were calculated using dens Read More

Starting from 2-hydroxybenzyl alcohol, a series of 2-arylbenzofurans have been synthesized and evaluated as acetylcholinesterase inhibitors at 23 αM by using modified colorimetric Ellman’s method. The reaction sequence was completed in four steps. All of the fourteen synthesized products were obtained in excellent yields without the need to tedious work-up step. In the last step, different derivatives were obtained by the su Read More

In an effort to develop potent antimicrobial agents, new thiazolyl hydrazone derivatives were synthesized and investigated for their inhibitory effects on pathogenic bacteria and yeasts. MTT assay was carried out to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. Among these compounds, 2-[2-[1-(4-(piperidin-1-yl)phenyl)ethylidene] hydrazinyl]-4-(4-fluorophenyl)thiazo Read More

Novel Leflunomide analogues were synthesized and evaluated in vivo against thioacetamide (TAA) induced liver fibrosis in rats. All the animals which were treated with the new analogues showed improved or comparable survival rates to those treated with Leflunomide. Animals which were treated with compounds 8d, 8e, 9 and 11 have shown improved liver parameters than Leflunomide treated animals. Histopathology of t Read More

The reaction of 1-heteroaryl-3-(tetrazolo[1,5-a]quinolin-4-yl)prop-2-en-1-ones with hydrazine hydrate in either ethanol or acetic acid furnished pyrazoline and N-acetylpyrazoline, respectively. N-phenylpyrazolines and pyrazoline-N-carbothioamides were synthesized, in good yields, from reaction of chalcons with phenylhydrazine and thiosemicarbazide, respectively. On the other hand, a series of 2-pyrazolin-1-ylthiazoles h Read More

Following our search for antimalarial compounds, novel series of piperazinylalcohol pyrrolo[ 1,2-a]quinoxaline derivatives 1-2 were synthesized from 2-nitroaniline or 2-amino-3- nitrophenol and tested for in vitro activity upon the intraerythrocytic stage of W2 and 3D7 Plasmodium falciparum strains. Biological results showed good antimalarial activity with IC50 ranging from 0.3 to 21.1 μM. In attempting to investigate the large Read More

The potency and aqueous solubility significantly affect the clinical use of Combretastatin A-4 and phenstatin analogs. A lot of Combretastatin A-4 analogs have good potency but they have been rejected in clinical trials due to low solubility. In this research work, cheminformatic approaches i.e., structure activity correlation by rational approach and computational approach (pharmacophore and atom based 3D QSAR), molecular Read More

Background: P-glycoprotein (P-gp) is the most important member of adenosine triphosphate (ATP) binding cassette (ABC) family and plays a critical role in facilitating the efflux mechanism to extrude various drug molecules. It is mostly present in pancreas, kidney, ovary, liver and breast. Piperine is a well known inhibitor of P-gp mediated efflux mechanism that makes it an efficient enhancer for promoting the bioavailability of a nu Read More

We previously reported the discovery of diphenylimidazoles as potent sodium channel blockers, potentially useful in the treatment of epilepsy. In this work we further explore the structural requirements necessary for the potency of these derivatives with the aim to understand which structural modifications of the original scaffold could be tolerated in order to retain activity. We have synthesized new compounds working on the Read More

A series of diethyl (3-((5-aryl-1H-1,2,4-triazol-3-yl)thio)propyl)phos-phonates (7a–t) has been synthesized in excellent yields by coupling diethyl (3-bromopropyl)phosphonate and 5-aryl-1H-1,2,4-triazol-3-thiones employing an efficient, green and nonconventional heterogeneous SO3Hcarbon catalyst derived from glycerol. In addition, a facile and green approach for the esterification of carboxylic acids by utilizing glycerol-base Read More

In an effort to develop a lead antimalarial compounds, a series of novel 2-aryl/heteroarylethyl-6-chloroquinoline-4-carboxylate derivatives (2a-j) were obtained by using quinoline-4-carboxylic acid derivatives which were produced by a simple one-pot synthesis of Pfitzinger reaction of isatin with Arylketones as intermediates which were finally esterified with ethanol in the presence of concentrated sulfuric acid to get the expe Read More