A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) β-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15μM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20μM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.

The alkaline hydrolysis reaction rates of 1, n -bis(4-cyanopyridinium)alkane derivatives C n bis(CP) 2+ with n = 3, 6, and 8 were studied and compared to the reaction rate of the N -methyl-4-cyanopyridinium (MCP + ). C 6 bis(CP) 2+ and C 8 bis(CP) 2+ obeyed the first-order kinetic law. However for C 3 bis(CP) 2+ data fitted to a consecutive two-step model reaction, the observed rate constants ( k obs ) of C 8 bis(CP) 2+ and C 6 bis(CP) 2+ are approximately 50% and 100%, respectively, higher than those for MCP + , an effect mainly assigned to the higher charge density of these two derivatives. For C 3 bis(CP) 2+ , the k obs of the second (slow) step is almost twofold the value observed for C 6 bis(CP) 2+ , whereas the first (fast) step is approximately six times higher. As for MCP, the hydrolysis of C n bis(CP) 2+ generates pyridone (P o ) and carbamidopyridinium (A + ) units. For C 3 bis(CP) 2+ , however at pHs above 11.5, one additional product is formed. From the existence of the new product and the kinetic evidence, a “sandwiched-type” complex with the OH − inserted between the rings is proposed. This structural effect in the C 3 bis(CP) 2+ due to the conformational effect justifies the (i) two kinetic steps, (ii) high rate constants, (iii) high P o /A + ratios, (iv) observed temperature and salt effects, and (v) the formation of the new product.

A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC50 values in the range of 1.15-8.46 mu m for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC50, in the range of 0.4 to 16.70 mu m.

In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β-carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4-methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC50 values of 0.48, 1.50 and 1.07 µM, respectively. An in silico study of the ADME properties of the novel synthesized β-carboline derivatives was also performed.

The aqueous alkaline reaction of 1,3-bis(4-cyanopyridinium)propane dibromide, a reactant constituted of two pyridinium rings linked by a three-methylene bridge, generates a novel compound,1 -(4-cyano-2-oxo-1,2-dihydro-1-pyridyl)-3-(4-cyano-1,2-dihydro-1-pyridyl)propane. The reaction pathway is attributed to the proximity of the OH- ion inserted between two pyridinium moieties, which occurs only in bis(pyridinium) derivatives connected by short methylene spacers, where charge-conformational effects are important.

The structure of the title compound, C19H17BrN2O3, consists of two cyclic groups, viz. 4-(methoxycarbonyl)phenyl and 6-(4-bromophenyl)-3-oxo-2,3,4,5-dihydropyridazin-4-yl, which are linked by a methylene spacer. The pyridazine ring is twisted and the dihedral angle between its mean plane and that of the bromophenyl mean plane is 17.2 (2)degrees. The 4-(methoxycarbonyl) phenyl group shows a quasi-planar conformation, where the dihedral angle between the mean planes of the phenyl ring and carboxylate ester group is 7.9 (4)degrees. Centrosymmetric intermolecular N-H center dot center dot center dot O hydrogen bonds form dimers. These are linked by C-Br center dot center dot center dot O=C interactions [Br center dot center dot center dot O = 3.10 (1) angstrom] to form a one-dimensional polymeric structure running along the [1 $(2) over bar $0] direction.

A series of β-carboline derivatives bearing a substituted-carbohydrazide moiety at C-3 were synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N(9)-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the benzylidene-carbohydrazides 3, 4, 11, 13, 16, 21 and 22 were the most active, possessing IC(50) less than 10 μM for six of the eight tumor cell lines assayed. The derivative 4 displayed the most significant activity toward all tested cell lines, with a remarkable cytotoxicity against renal (786-0) cell lines (IC(50)=0.04 μM). Compound 4 was assayed for its in vivo antineoplastic activity in the Ehrlich solid carcinoma assay.

5-(4-pyridinyl)-1,3,4-oxadiazole-2-thiol (Hpyt) spontaneously adsorbs on gold forming SAMs (self-assembled monolayers) that, based on STM (Scanning Tunneling Microscopy) and electrochemical data, contain pinholes through which [Fe(CN)6]4- and [Ru(NH3)6]3+ probe molecules access the underlying gold electrode. For the former molecule, the dependence of the faradaic current on the electrolyte solution pH value allowed the evaluation of the surface pKa as 4.2. The thermodynamic parameters DHads and DGads for the Hpyt adsorption process could be described by the Langmuir model and were calculated as -20.01 and -39.39 kJ mol-1, respectively. Electrodic redox reaction of cytochrome c metalloprotein was accessed by using the Hpyt SAM with a heterogeneous electron transfer rate constant of 2.29 × 10-3 cm s-1.

The synthesis of new 1,2,4- and 1,3,4-oxadiazole derivatives as potential nonpeptide angiotensin II receptor antagonists is described. The quinoxalinone systems used as the "northern moiety in these compounds were alkylated through a liquid/liquid phase-transfer catalysis protocol, with good yields and high nitrogen- to oxygen-alkylated product (N/O) ratios.

The trans-[RuCl2(dppb)(1,4-dt)], mer-[RuCl3(dppb)(1,4-dt)] and [{RuCl3(dppb)}2(μ-(1,4-dt))] complexes were synthesized and characterized by spectroscopic and electrochemical techniques. The [RuCl2(dppb)] moiety is the first example of a metallic system that form complexes with the 1,4-dithiane molecule acting as bidentate, monodentate and bridged ligand.

Aiming at the development of novel NO donors, the synthesis and reactivity of the trans-[Ru(bpy)2(SO3)(NO)](PF6) and cis-[Ru(bpy)2(L)(NO)](PF6)n complexes (L = imidazole, isonicotinamide, or sulfite ions) were investigated. The complexes were characterized and the NO release capabilities were evaluated. The rate constant for NO dissociation for the cis-[Ru(bpy)2(SO3)(NO)]+ complex is k = 2.0·10–3 s–1. The cis and trans- [Ru(bpy)2(SO3)(NO)]+ complexes showed promising physical-chemical properties towards nitric oxide generation, and great stability towards hydroxide attack in the 2.0–9.0 pH range. The reduction potential of the {RuNO}6/7 process of the cis and trans-[Ru(bpy)2(SO3)NO]+ complexes (E1/2 =–0.14 and –0.34 V vs. Ag/AgCl) is appropriated for reduction in vivo by biological reducing agents, with consequent NO release. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

A novel series of compounds structurally related to nonpeptide angiotensin II (AII) receptor antagonists derived from 4,5-dihydro-3(2H)pyridazinones has been prepared. In these compounds, the spacer is linked to the C4 of the heterocyclic ring.

The structures of two oxadiazole derivatives, methyl 2-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]benzoate (1) and methyl 2-[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]benzoate2, used as spacers in the synthesis of new potential non-peptide angiotensin receptor antagonists have been determined by X-ray crystallography. In both compounds π–π interactions were observed between the oxadiazole rings and the phenyl rings of neighboring molecules. In the crystal packing of the oxadiazole 2 two C–H⋯O interactions are present.

Intramolecular nonbonded interactions have been observed in the crystalline structures of 6-ethoxy-2-trifluoroacetyliminobenzothiazoline (4) (S⋯O close contact) and 6-ethoxy-2-trifluorothioacetyliminobenzothiazoline (5) (S⋯S close contact). Density functional B3LYP/6-311G∗∗ calculations were performed for all conformers and tautomers of 4 and 5 in order to explain the preference for the S⋯O and S⋯S close contact structures. The calculations agree with the observed crystallographic structures only when solvent effects are included via a continuum model, thus showing the importance of the solvent effects to establish the correct relative energies.

A novel series of compounds structurally related to non-peptide angiotensin II (AII) receptor antagonists has been prepared. In these compounds. the 'spacer' phenyl ring commonly found in almost all All receptor antagonists was replaced by 1,2,4- and 1,3,4-oxadiazole rings.

Reaction of 5-(2-pyridyl)tetrazole with 1,3-dibromopropane afforded three regioisomeric multidentate ligands L1, L2 and L3 containing two tetradentate pyridyl/tetrazolyl units linked by a flexible propylene spacer. These compounds were fully characterized by IR, 1H and 13C NMR spectroscopy and elemental analysis. The crystal structure of L1 was determined. With Cu(II), L1 formed a trinuclear complex Cu3(L1)2Cl6. Its structure was determined crystallographically. In the complex, the three copper atoms are found to be in a strict linear arrangement, with the ligand bridging two adjacent copper atoms. The central copper ion is six-co-ordinated. The co-ordination spheres of the terminal copper atoms are distorted square pyramidal. Inter and intramolecular π,π-stacking interactions are observed in the free ligand and in complex 1.

The synthesis, characterization and mesogenic behaviour of the copper(II) and oxovanadium(IV) complexes derived from phenyltetrazole and benzothiazole and their corresponding ligands are reported. The ligands did not exhibit mesomorphism, whereas the complexes form monotropic smectic A and smectic C mesophases. The mesophases were identified according to their textures by optical microscopy.

The title compound, C13H12N2O5, is a key intermediate in the synthesis of mesogens, which are derivatives of phenyloxadiazole. The oxadiazole and phenyl rings are planar to within 0.003 (2) and 0.010 (7) Angstrom, respectively. The dihedral angle between the least-squares planes through the rings is 10.9(1)degrees.

The structure of the title compound [4-(5-tetrazolyl)-1,3-benzenediol sesquihydrate, C7H6N4O2.3/2H(2)O] which crystallizes with two tetrazolylbenzenediol molecules per asymmetric-unit together with three water molecules, has been determined by single-crystal X-ray diffraction at room temperature. The two molecules are linked through a hydrogen-bonded network to water molecules, forming layers extending the bc face of the unit cell.