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A series of novel 1-(4-substitutedbenzoyl)-4-(4-chlorobenzhydryl)piperazine derivatives 5a–g was designed by a nucleophilic substitution reaction of 1-(4-chlorobenzhydryl)piperazine with various benzoyl chlorides and characterized by elemental analyses, IR and 1H nuclear magnetic resonance spectra. Cytotoxicity of the compounds was demonstrated on cancer cell lines from liver (HUH7, FOCUS, MAHLAVU, HEPG2, HEP3B), breast (MCF7, BT20, T47D, CAMA-1), colon (HCT-116), gastric (KATO-3) and endometrial (MFE-296) cancer cell lines. Time-dependent cytotoxicity analysis of compound 5a indicated the long-term in situ stability of this compound. All compounds showed significant cell growth inhibitory activity on the selected cancer cell lines.

Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer’s disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) to simultaneously target AD-related receptors. We built a library of 70 compounds, sequentially screened for ChEI, and determined σ1R, σ2R, NMDAR-GluN2B binding affinities, and P2X7R antagonistic activities. Nine fulfilled in silico drug-likeness criteria and did not display toxicity in three cell lines. Seven displayed cytoprotective activity in two stress-induced cellular models. Compared to donepezil, six showed equal/better synaptic protection in a zebrafish model of acute amyloidosis-induced synaptic degeneration. Two P2X7R antagonists alleviated the activation state of microglia in vivo. Permeability studies were performed, and four did not inhibit CYP450 3A4, 2D6, and 2C9. Therefore, four ChEI-based lead MTDLs are promising drug candidates for synaptic integrity protection and could serve as disease-modifying AD treatment. Our study also proposes zebrafish as a useful preclinical tool for drug discovery and development.

Fused pyrimidine derivativesFused pyrimidine derivatives R 0515 Synthesis and in vitro Calcium Antagonist Activity of 4-Aryl-7,7-dimethyl/ 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione Derivatives. -Title compounds (IV) (25 examples) are prepared by one-pot condensation of ureas (I), aromatic aldehydes (II) and cyclohexanedione (III) under strongly acidic conditions according to the Biginelli reaction. Their calcium antagonist activity is tested in vitro on isolated rat ileum and lamb carotid artery. Compounds (IVd) and (IVe) are the most active derivatives. -(YARIM, M.; SARAC*, S.; KILIC, F. S.; EROL, K.; Farmaco 58 (2003) 1, 17-24; Dep. Pharm. Chem., Fac. Pharm., Hacettepe Univ., TR-06100 Ankara, Turk.; Eng.) -F. Santoso 22-159

In this study, the synthesis of some new 2‐thioxo‐1,2,3,4‐tetrahydropyrimidines and their condensed derivatives, thiazolo[3,2‐α] pyrimidines, are described. The structures of the compounds were confirmed by IR, 1H‐NMR, 13C‐NMR, and mass spectroscopy. The direct high‐performance liquid chromatographic separation of the compounds on derivatized cellulose chiral stationary phases such as cellulose tris(3,5‐dimethylphenylcarbamate) (OD), cellulose tris(4‐methylphenylcarbamate) (OG), and cellulose tris(4‐methylbenzoate) (OJ) was studied. All of the compounds were screened for their antiinflammatory activity and also investigated histopathologically. Compounds 3 and 1a were found to be the most promising antiinflammatory agents in this group.

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This study presents the synthesis of nineteen 1-(substitutedbenzoyl)-4-benzhydrylpiperazine and 1-[(substitutedphenyl)sulfonyl]-4-benzhydrylpiperazine derivatives. In vitro cytotoxic activities of the compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Among the test compounds, benzamide derivatives had high cytotoxic activity whereas sulfonamide derivatives showed variable 50% growth inhibition (GI50).

Synthesis, characterization and cytotoxic activities of ten benzothiazole-piperazine derivatives were reported. In vitro cytotoxic activities of compounds were screened against hepatocellular (HUH-7), breast (MCF-7) and colorectal (HCT-116) cancer cell lines by sulphorhodamine B assay. Based on the GI50 values of the compounds, most of the benzothiazole-piperazine derivatives are active against HUH-7, MCF-7 and HCT-116 cancer cell lines. Aroyl substituted compounds 1h and 1j were found to be the most active derivatives. In addition, further investigation of compounds 1h and 1j by Hoechst staining and FACS revealed that these compounds cause apoptosis by cell cycle arrest at subG1 phase.