Synthesis and Antileukemic Activity of 1-((S)-2-Amino-4,5,6,7-tetrahydrobenzo[d]thiazol-6-yl)-3-(substituted phenyl)urea Derivatives

Heterocyclic urea derivatives play an important role as anticancer agents because of their good inhibitory activity against receptor tyrosine kinases (RTKs), raf kinases, protein tyrosine kinases (PTKs), and NADH oxidase, which play critical roles in many aspects of tumorigenesis. Benzothiazole moiety constitutes an important scaffold of drugs, possessing several pharmacological functions, mainly the anticancer activity. Based on these interesting properties of benzothiazoles and urea moiety to obtain new biologically active agents, we synthesized a series of novel 1-((S)-2-amino-4,5,6.7-tetrahydrobenzo[d]thiazol-6-yl)-3-(substituted phenyl)urea derivatives and evaluated for their efficacy as antileukemic agents against two human leukemic cell lines (K562 and Reh). These compounds showed good and moderate cytotoxic effect to cancer cell lines tested. Compounds with electron-withdrawing chloro and fluoro substituents on phenyl ring showed good activity and compounds with electron-donating methoxy group showed moderate activity. Compound with electron-withdrawing dichloro substitution on phenyl ring of aryl urea showed good activity. Further, lactate dehydrogenase (LDH) assay, flow cytometric analysis of annexin V-FITC/propidium iodide (PI) double staining and DNA fragmentation studies showed that compound with dichloro substitution on phenyl ring of aryl urea can induce apoptosis.

An alpha-aminomethyl carbanion equivalent via a novel Barbier reaction: (1H-naphtho[1,8-de]-1,2,3-triazin-2-yl)methyl anion

A novel sonication-promoted Barbier reaction putatively generated the titled species from the corresponding naphthotriazinylmethyl chloride and magnesium in THF: its formal addition to a variety of carbonyl compounds in situ occurred in excellent yields. Subsequent catalytic hydrogenolysis of the triazine moiety demasked the amine, thus defining a route to various phenylethylamines (including the alkaloid 'mescaline'), or ethanolamines (in two cases), in excellent overall yields. (C) 2000 Elsevier Science Ltd. All rights reserved.

Selective para metalation of unprotected 3-methoxy and 3,5-dimethoxy benzoic acids with n-butyl lithium-potassium tert-butoxide (LIC-KOR): synthesis of 3,5-dimethoxy-4-methyl benzoic acid

The potassium salt of 3-methoxy and 3,5-dimethoxy benzoic acids undergoes deprotonation at the position para to the carboxylate group selectively when treated with LIC-KOR in THF at -78 degrees C and it has been extended to the synthesis of 3,5-dimethoxy-4-methyl benzoic acid. (C) 2000 Elsevier Science Ltd. All rights reserved.

Chiral synthons from carvone, Part 40. A simple, enantiospecific approach to both enantiomers of 1 alpha,25-dihydroxyvitamin D-3 A-ring precursors from R-carvone

A simple and direct approach to both enantiomeric series of A-ring derivatives of 1 alpha,25-dihydroxyvitamin D-3 and the corresponding 1 alpha,3 alpha-derivatives, starting from the abundantly available R-carvone, is described. (C) 2000 Elsevier Science Ltd. All rights reserved.

Bi2−xPbx(Ca, Sr)n+1CunO2n+4+δ (n = 1, 2, 3, and 4) family of superconductors

Superconducting oxides of the Bi1.5Pb0.5(Ca, Sr)n+1CunO2n+4+δ series with n = 1, 2, 3 and 4 have been characterized. The superconducting transition temperature increases markedly with n up to n = 3, but the Tc of the n = 4 member is not much higher than that of the n = 3 member. The Tc does not change significantly in Bi2−xPbxCaSr2Cu2O8+δ with x (0.1 < x ≤ 0.5).

A Ca2+-sensitive cyclic-3',5'-nucleotide phosphodiesterase from sheep lung modulated by a tightly bound endogenous calmodulin.

Highly purified sheep lung cyclic-3',5'-nucleotide phosphodiesterase was sensitive to Ca2+/EGTA but insensitive to exogenous calmodulin. The Ca2+-sensitivity was inhibited by trifluoperazine. Heat-treated enzyme could activate a calmodulin-deficient phosphodiesterase, suggesting the presence of endogenous calmodulin in sheep lung cyclic-3',5'-nucleotide phosphodiesterase, possibly associated with the enzyme in a Ca2+-independent manner.

Crystal structure of 2-thiophene-2-yl-3(thiophene-2-carboxylideneamino)-1,2-dihydroquinazolin-4(3H)-one and the synthesis, spectral and thermal studies of its transition metal(II) complexes

The synthesis of manganese(II), cobalt(II), nickel(II), copper(II), zinc(II) and cadmium(II) complexes of a new ligand 2-thiophene-2-yl-3(thiophene-2-carboxylidene-amino)-1,2-dihydroquinazolin-4(3H)-one (TTCADQ) is described. The ligand and metal complexes were characterized by elemental analysis, conductivity measurements, spectral (u.v.-vis., i.r., 1D n.m.r., 2D hetcor and e.p.r.) and thermal studies. The formation of 1,2-dihydroquinazolin-4(3H)-one rather than hydrazone, in the reaction of aromatic aldehyde and o-aminobenzoylhydrazide is proved by single crystal X-ray diffraction and 2D hetcor n.m.r. studies. On the basis of elemental analysis, u.v.-vis.spectroscopy and magnetic moment studies, six coordinate geometry for all the complexes was proposed. The i.r. spectral studies reveal the bidentate behaviour of the ligand.

Interaction of 3-hydroxybenzoate-6-hydroxylase with cibacron blue

Cibacron blue is a potent inhibitor of 3-HBA-6-hydroxylase at a concentration < 1 mu M. Kinetic analyses revealed that at a concentration below 0.5 mu M the dye behaves as an uncompetitive inhibitor with respect to 3-HBA and competes with NADH for the same site on the enzyme. The alteration of the near-UV CD spectrum and quenching of the emission fluorescence of the enzyme by cibacron blue indicates a significant alteration in the environment of aromatic amino acid residues due to a stacking interaction and subtle conformatiodnal changes in the enzyme. The concentration-dependent quenching of the intrinsic fluorescence of the enzyme by cibacron blue was employed to determine the binding parameters such as association constant (K-a) and stoichiometry (r) for the enzyme-dye complex.