Current Issue : July - September Volume : 2011 Issue Number : 3 Articles : 13 Articles
Various derivatives of imidazole-2-thione are reported to possess antimicrobial activity. A Quantitative Structure Activity Relationship (QSAR) study was carried out on 1-tolyl-3-aryl-4-methylimidazole-2-thiones to examine the structural requirement for antimicrobial activity against E coli. The QSAR study was performed using CS Chem. Office 2005 and vLife MDS 3.5 molecular modeling software. Energy minimization of all the derivatives were carried out using CS Chem. Office 2001 by Allingers MM2 force field where the Root Mean Square Gradient (RMS) at 0.1 kcal mol-1 and semiemperical AM1 Hamiltonian method (MOPAC module). The thermodynamic, steric and electronic descriptors were calculated using vLife MDS 3.5 molecular modeling software. Antibacterial activity data and various molecular descriptors were taken as dependent and independent variables respectively and correlation was established between them by employing stepwise multiple linear regression method. In order to explore the predictive power of the selected descriptors, the data set of 25 imidazole-2-thione derivatives was divided into training set (18 compounds) and test set (7 compounds). Several stepwise multiple linear regressions were performed using vLifeMDS 3.5, in order to obtain QSAR models. Among the many correlations generated, statistically significant models were selected based on various statistical measures employed for the evaluation of the significance of the model. The orthogonality of the descriptors in the selected correlations was confirmed by the calculation of overall correlation matrix. The results of the study emphasize the importance of electronic parameter on antibacterial activity of imidazolidine-2-thiones against E coli. Polarizability and dipole moment of the molecules have major effects on the antibacterial activity of 1-tolyl-3-aryl-4-methylimidazole-2-thiones....
The development of new therapies to treat hypertension effectively is currently an intensive area of research. To achieve this objective quantitative structure activity relationship (QSAR) study was carried out on a reported series of phthalazine derivatives as alpha-1d antagonist, as it provides the rationale for the changes in the pharmacophore to have more potent and less toxic analogue. In this article, we report 2D and 3D QSAR studies for the set of 20, alpha-1d antagonist. For the 2D QSAR studies we used stastical methods like multiple linear regression (MLR), principle component regression (PCR), and partial least square regression (PLSR) technique. The 3D QSAR model was developed by Simulated Annealing kohonen Nearest Neighbour Molecular Field Analysis (SA kNN MFA). By performing 2D QSAR, we found that multiple linear regression method showed best statistical result when compared with other methods. The model has shown correlation coefficient (r2), cross validation (q2) and external validation (pred_r2) values of 0.8639, 0.7839 and 0.8621, respectively. The 3D QSAR models were generated to study the effect of steric, electrostatic and hydrophobic descriptors on alpha-1d antagonist activity. The model with good external and internal productivity for the training and test set that has shown cross validation (q2) and external validation (pred_r2) values of 0.6053 and 0.8621, respectively. The steric and hydrophobic descriptors at the grid points S_517 and H_504 play an important role in the design of new molecule. Thus 2D and 3D QSAR studies were found to reliable clues for further optimization of phthalazine pharmacophore as alpha-1d antagonist....
Combinatorial chemistry (or Combi-Chem) is an innovative method of synthesizing many different substances quickly and at the same time. Combinatorial chemistry contrasts with the time-consuming and labor intensive methods of traditional chemistry where compounds are synthesized individually, one at a time Combinatorial chemistry was developed to produce the large numbers of compounds required for high throughput screening. It allows the simultaneous synthesis of a large number of the possible compounds that could be formed from a number of building blocks. The products of such a process are known as a combinatorial library. Libraries may be a collection of individual compounds or mixtures of compounds. Screening the components of a library for activity using high throughput screening techniques enables the development team to select suitable compounds for a more detailed investigation by either combinatorial chemistry or other methods. Different methods of combi chemistry are solid phase, solution phase synthesis, parallel method and biological methods....
Based on the structure of three previously established lead compounds, fifteen selected chalcones were synthesized and evaluated for their multidrug resistance (MDR) reversal activity on mouse lymphoma cells. The most active chalcones were stronger revertants than the positive control, verapamil. In the model of combination chemotherapy, the interactions between the anticancer drug doxorubicin and two of the most effective compounds were measured in vitro, on human MDR1 gene transfected mouse lymphoma cells, showing that the type of interaction for one of these compounds was indifferent while that for the other one was additive. Furthermore, two chalcones inhibited 50% of cell proliferation in concentration of around 0.4?�µg/mL and were from 2- to 100-fold more active than the most chalcones. The structure-activity relationships were obtained and discussed in view of their usefulness for the design of chalcone-like P-gp modulators and drugs able to treat resistant cancers....
The neonatal ventral hippocampal lesion (nVHL) has been widely used as an animal model for schizophrenia. Rats with an nVHL show several delayed behavioral alterations that mimic some symptoms of schizophrenia. Sprague-Dawley (SD) rats with an nVHL have a decrease in D3 receptors in limbic areas, but the expression of D3 receptors in Wistar (W) rats with an nVHL is unknown. The 7-Hydroxy-2-(N,N-di-n-propylamino) tetralin (7-OH-DPAT) has been reported as a D3-preferring agonist. Thus, we investigated the effect of (\r\n�±\r\n)-7-OH-DPAT (0.25?mg/kg) on the motor activity in male adult W and SD rats after an nVHL. The 7-OH-DPAT caused a decrease in locomotion of W rats with an nVHL, but it did not change the locomotion of SD rats with this lesion. Our results suggest that the differential effect of 7-OH-DPAT between W and SD rats with an nVHL could be caused by a different expression of the D3 receptors. These results may have implications for modeling interactions of genetic and environmental factors involved in schizophrenia....
Parkinson's disease (PD) is a progressive extrapyramidal motor disorder. Pathologically, this disease is characterized by the selective dopaminergic (DAergic) neuronal degeneration in the substantia nigra. Correcting the DA deficiency in PD with levodopa (L-dopa) significantly attenuates the motor symptoms; however, its effectiveness often declines, and L-dopa-related adverse effects emerge after long-term treatment. Nowadays, DA receptor agonists are useful medication even regarded as first choice to delay the starting of L-dopa therapy. In advanced stage of PD, they are also used as adjunct therapy together with L-dopa. DA receptor agonists act by stimulation of presynaptic and postsynaptic DA receptors. Despite the usefulness, they could be causative drugs for valvulopathy and nonmotor complication such as DA dysregulation syndrome (DDS). In this paper, physiological characteristics of DA receptor familyare discussed. We also discuss the validity, benefits, and specific adverse effects of pharmaceutical DA receptor agonist....
Identification of selective influenza viral sialidase inhibitors is highly desirable in order to minimize or avoid the adverse effects due to the possible inhibition of endogenous human sialidases. We recently reported the evaluation of C9 N-acyl Neu5Ac2en mimetics as probes for human sialidases. Herein, we describe the in vitro activity of the same set of C9 N-acyl Neu5Ac2en mimetics against sialidases expressed by influenza virus A/PR/8/34 (H1N1), A/Memphis/1/72 (H3N2), and A/Duck/313/78 (H5N3) strains. Compound 8 is identified as a promising starting point for the development of viral sialidase selective inhibitors. Multiple sequence alignment and molecular docking techniques are also performed to explore the plausible interaction of compound 8 with viral sialidases....
From well-known antioxidants agents, we developed a first pharmacophore model containing four common chemical features: one aromatic ring and three hydrogen bond acceptors. This model served as a template in virtual screening of Maybridge and NCI databases that resulted in selection of sixteen compounds. The selected compounds showed a good antioxidant activity measured by three chemical tests: DPPH radical, \r\nO H radical, and superoxide radical scavenging. New synthetic compounds with a good correlation with the model were prepared, and some of them presented a good antioxidant activity....
In the present investigation, A series Novel Schiff’s bases 3-[substituted (phenyl methylidene] amino} ethyl) amino] quinoxalin-2(1H)-one have been synthesized by Phillips condensation mechanism. And in further step of synthesis Schiff’s bases were synthesized by reacting with series aromatic aldehydes. Final derivatives were screened for their in- vitro anti bacterial activity against range of Gram positive and Gram negative as well as for their anti fungal activity against a clinical isolate of Candida albicans species. All the compounds were characterized by IR and 1H NMR spectroscopic data. The compound IIIe is highly active against E. coli. The compound IIIe and IIIf highly active against B.amylase .compounds IIIa, IIIf are highly active against P. aerogenosa. The compound IIIb and IIIf highly active against fungal stain C.albicans....
The reaction of substituted aromatic aldehydes with ethylacetoacetate in presence of ammonia solution yielded diethyl-2,6-dimethyl-4-(substitutedphenyl)1,4-dihydropyridine3,5-dicarboxylate (1), which on treatment with hydrazine hydrate produced 2,6-dimethyl-4-(substituted phenyl)-1,4-dihydropyridine-3,5-dicarbohydrazide (2), cyclization with substituted benzoic acids in presence of phosphorous oxychloride produced 2,6-dimethyl-4-(substitutedphenyl)3,5-[bis-(5’-substitutephenyl1’,3’,4’-oxadiazolo)] 1, 4dihydropyridine (3a-l). Purity was checked by TLC and the chemical structures of synthesized compounds were elucidated by their IR, 1H NMR analysis data. The synthesized compounds were screened for Anti-inflammatory activity....
In the present investigation, a series of novel substituted 6-phenyl-1,8a-dihydro[1,2,4]triazolo[1,5-a]pyridine derivatives (5a-m) have been synthesized via Suzuki-Miyaura coupling reaction. The title compounds were synthesized starting from 5-bromopyridin-2-amine (1). The reaction of compound 1 with hydroxyl amine hydrochloride furnished N-(5-bromopyridin-2-yl)-N'- hydroxylimidoformamide (2), which upon further reaction with acetic anhydride furnished 6-bromo-1,8a-dihydro[1,2,4]triazolo[1,5-a]pyridine (3). The treatment of 6-bromo-1,8a-dihydro[1,2,4]triazolo[1,5-a]pyridine (3) with diverse boronic acids (4a-m) afforded the title compounds (5a-m). The structures of newly synthesized compounds were established by 1HNMR, Mass spectral data and elemental analysis. Further these compounds were screened for antimicrobial activity. The Antimicrobial activity results revealed that compounds 5a, 5e, 5f, 5g, 5l and 5m have shown good activity against all tested organisms at both concentrations whereas compound 5j showed good activity against only fungal species Aspergillus Niger and Trichoderma Virdae....
A series of novel oxazolone derivatives (3f to 3j) were synthesized by refluxing equimolar quantity of acetyl glycine, substituted aromatic and hetero aromatic aldehyde in presence of acetic anhydride and sodium acetate .The synthesized compounds were screened for oral hypoglycemic activity by alloxan induced model in male Sprague dawley rats. All the compounds were effective except 3h as compared with standard glibenclamide. The results are statistically treated for its significance....
The novel selective D1 dopaminergic full agonists A-68930, A-77636 were discovered by the synthesis of molecules to probe the bioactive conformation of the partial agonist SKF-38393, by the use of this information to add D1 affinity and selectivity to a screening hit, and by traditional medicinal chemistry exploration of structure-activity relationships. The subsequent design of A-86929 and ABT-413 capitalized on these results, recently disclosed agonists, and traditional medicinal chemistry....
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