Letters in Drug Design & Discovery - Volume 8, Issue 9, 2011

A focused library of more than 90 N-benzenesulfonyl derivatives of heterocycles was generated by a practical and efficient solution-phase parallel synthesis. The methodology used led to pure compounds in a shorter time compared with the classical synthesis. The reaction conditions were carefully studied to achieve a one-pot method that allows the use of automated equipment. A simple chromatography-free workup proc Read More

A series of isonicotinic acid hydrazide derivatives (1-14) was synthesized and tested for their in vitro antimycobacterial activity against Mycobacterium tuberculosis and the compounds with bromo, N2-2,4-hexadienoyl, N2-lauryl and N2-octadecanoyl groups were found to be the most effective, especially isonicotinic acid-N'-octadecanoyl hydrazide (12) was more active than the standard drug isoniazid. The results Read More

In this study, we aimed at the synthesis of new N,N-disubstituted dithiocarbamoic acid, 2-[(9-ethyl-9Hcarbazol- 3-yl)amino]-2-oxoethyl esters and their antimicrobial evaluations. The chemical structures of the compounds were elucidated by IR, 1H NMR, 13C NMR, MS spectral data and elemental analysis. The antibacterial and antifungal activities of the synthesised derivatives were tested against Gram (+), Gram (-) bact Read More

A series of andrographolide (Andro) derivatives (3-14) were designed, synthesized and screened for their antibacterial activities against both gram-positive and gram-negative bacteria in vitro. The most promising compounds 14a-c exhibited at least eight-fold stronger antibacterial activities compared to Andro. Especially, Compound 14a, which showed 32-fold stronger antibacterial activity than Andro, has a potency to be a new lead.

Some benzothiazole derivatives bearing piperazine and dithiocarbamate moieties were synthesized in order to investigate their anticancer activity. The structures of the obtained compounds were confirmed by spectral data and elemental analysis. Synthesized compounds were evaluated for their anticancer activity at the National Cancer Institute against a panel of approximately 60 different human tumor cell lines derived fro Read More

The present anticancer research demands more potent anticancer agents with fewer side effects than the existing ones. A series of novel substituted thiazole and benzothiazole containing nitrogen mustards (5-8; 15-17; 22-23) were synthesized and the structures of the compounds were analyzed by IR, NMR and mass spectras. Their in-vitro cytotoxicity against human lung carcinoma (A549) was investigated by MTT Read More

Novel fluorine-containing pyrazolines (2a-2g) and pyrazoles (5a-5e) were synthesized and evaluated for their cytotoxicity in vitro in a panel of four human cancer cell lines using Sulforhodamine B (SRB) assay. Though the compounds showed varying degrees of cytotoxicity in different cell lines, it was noteworthy that the 4H pyrazoles (5a-5e) were distinguished by their potent and selective action against MCF7 breast cancer cell line.

Several physicochemical and topological descriptors used for estimating anti-cancer activity of benzothiazole derivatives indicated that the use of physicochemical parameters alone yield most appropriate model for modeling the activity.

To search for potential anti-cancer analogs, 16 aromatic esters of 4'-demethyl-4-deoxypodophyllotoxin (6a-p) were synthesized and tested their cytotoxicity on six cancer cell lines. The results indicated that all derivatives showed potent cytotoxic activity against A-549 cell line with IC50 values of 0.00009-0.037 μg/mL.

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which is being evaluated clinically for cancer therapy, selectively induces apoptosis in tumor cell lines without causing toxicity to normal cells. However, its therapeutic potential is limited by occurring resistance in a majority of lung carcinoma, breast and prostate cells. Various chemotherapeutic drugs have been found to enhance TRAIL-induced apoptosis. The object Read More

A set of one hundred and twenty two coumarin derivatives with TNF-α inhibitory activity was subjected to the two dimensional quantitative structure activity relationships (2D-QSAR) studies using MDS 3.0 drug designing module with Multiple Linear Regression (MLR), Principle Component Regression (PCR) and Partial Least Square Regression (PLS) analysis being carried out. Among these three methods, PCR-model has com Read More

Comparative molecular field analysis (CoMFA) was carried out on Carbonic anhydrase inhibitor hCA IX- tumor-associated (Hypoxia). Database contains a series of aromatic benzene sulfonamides incorporating 1, 3, 5-triazine moieties derivative. This study correlates the inhibitory activities of structurally related 1, 3, 5-triazine moiety derivatives derived to Tripos standard in CoMFA. The data base alignment conformation yiel Read More

A series of 1-arylpyrazole and their N- and S- glycosides has been synthesized. The key step is the synthesis of 3- (furan-2-yl)-1-phenyl-1H-pyrazole-4-carbaldehyde 1 via Vilsmeier -Haack reaction on the hydrazone of 2-acetylfuran. Compound 1 was transformed to N,N-dialkyl acrylamide (and/or acetamide) derivatives 3a, 3b and 6 through reaction with malonic acid and application of Willgerodt-Kindler reaction followed by reacti Read More

4, 5, 6, 7-Tetrahydropravastatin and its sodium salt as the hydrogenated derivatives of pravastatin were evaluated as HMG-CoA reductase inhibitor in vitro and in vivo, and they exhibited similar antihyperlipidaemic activity to pravastatin. The results could be regarded as a particular case to the reported SARs of statins up to now.

Results of the modelling of thiosemicarbazone-based inhibitors of ES suggest that these compounds interact with the calcium ion whilst undergoing hydrogen bonding interaction with the active site - the extent of H-bonding determining the overall inhibitory activity. Novel inhibitors were designed, synthesised and evaluated and found to possess potent inhibitory activity.