Facile Synthesis and in Vitro Cytotoxic Evaluation of Novel Thiadiazole,Pyrazole, and Dithiole-Androstane Derivatives

In the aim of identifying new steroidal cytotoxic agents with potential antiproliferative activity against hepatoma cell lines (Hep-G₂), we synthesized modified steroids containing the thiadiazole, pyrazole, or dithiole moiety. Epiandrosterone 1 reacted with carbon disulfide and sodium hydride to furnish α-oxoketene dithio-disodium salt 2. Treatment of 2 with the hydrazonoyl halides 5a–d produced the thiadiazole anellated androstanone 7a–d, respectively. The reaction of 1 with hydrazine hydrate produced the hydrazide adduct 8, which cyclized upon reflux in acetic acid to form the condensed pyrazoloandrostanone derivative 9. Interaction of 8 with carbon disulfide and sodium hydride formed the disodium salt 10, which reacted with ethylchloroacetate to furnish the final adduct, dithioloandrostane derivative, 13. Compounds 7a, 7d, 9, and 13 were examined for their cytotoxicity against a panel of hepatoma cell lines (Hep-G₂) using MTT assay. The results provide that, at incubation time 72 h, in DMSO, compound 7d (50 μ mol/mL) showed the most significant cytotoxic effect at P < 0.05. The higher dose (100 μ mol/mL) of compound 7d, at 48 h incubation, reversed the effect causing resistance and the growth rate return to the control level.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

First Synthesis of the Inherently Chiral Trans-4′ Bisadduct of C59N Azafullerene by Using Cyclo-[2]-dodecylmalonate as a Tether

The multiaddition chemistry of azafullerene C₅₉N has been scarcely explored, and the isolation of pure bisadducts is in its infancy. Encouraged by the recent regioselective synthesis of the inherently chiral equatorial_face bisadduct of C₅₉N, we focused on the isolation of the first trans-4 bisadduct in a simple two-step approach. The first regioselective synthesis of the trans-4 bisadduct of C₅₉N by using cyclo-[2]-dodecylmalonate as a tether is now reported. The newly synthesized bisadduct has C₁ symmetry, as evidenced by ¹³C NMR, while X-ray crystallography validated the trans-4′ addition pattern. Furthermore, the inherently chiral trans-4′ C₅₉N bisadduct was enantiomerically resolved, and the mirror-image relation of the two enantiomers was probed by circular dichroism spectroscopy. Finally, UV-Vis and redox assays suggested that the addition pattern has a reflection in the light-harvesting and redox properties of the bisadduct.     

Biochemical Properties of Tyrosinase from Aspergillus terreus and Penicillium copticola; Undecanoic Acid from Aspergillus flavus,an Endophyte of Moringa oleifera,Is a Novel Potent Tyrosinase Inhibitor

Tyrosinase is a copper-containing monooxygenase catalyzing the O-hydroxylation of tyrosine to 3,4-dihydroxyphenylalanine then to dopaquinone that is profoundly involved in melanin synthesis in eukaryotes. Overactivation of tyrosinase is correlated with hyperpigmentation that is metabolically correlated with severe pathological disorders, so, inhibition of this enzyme is the most effective approach in controlling the overproduction of melanin and its hazardous effects. Thus, searching for a powerful, selective inhibitor of human tyrosinase to limit the hyper-synthesis of melanin is a challenge. Unlike the difficulty of overexpression of human tyrosinase, using fungal tyrosinase as a model enzyme to the human one to evaluate the mechanistics of enzyme inhibition in response to various compounds is the most feasible strategy. Thus, the purification of highly catalytic-efficient fungal tyrosinase, exploring a novel inhibitor, and evaluating the mechanistics of enzyme inhibition are the main objectives of this work. Aspergillus terreus and Penicillium copticola were reported as the most potential tyrosinase producers. The biochemical properties suggest that this enzyme displays a higher structural and catalytic proximity to human tyrosinase. Upon nutritional bioprocessing by Plackett–Burman design, the yield of tyrosinase was increased by about 7.5-folds, compared to the control. The purified tyrosinase was strongly inhibited by kojic acid and A. flavus DCM extracts with IC₅₀ values of 15.1 and 12.6 µg/mL, respectively. From the spectroscopic analysis, the main anti-tyrosinase compounds of A. flavus extract was resolved, and verified as undecanoic acid. Further studies are ongoing to unravel the in vivo effect and cytotoxicity of this compound in fungi and human, that could be a novel drug to various diseases associated with hyperpigmentation by melanin.     

Synthesis,characterization, and biological investigation of new mixed-ligand complexes

A novel series of mixed-ligand complexes of 5,5′-{(1E,1E′)-1,4-phenelynebis(diazene-2,1-diyl)}bis(quinolin-8-ol) (H₂L₁) as a primary ligand and 4-aminoantipyrine(L₂) as a secondary ligand with Mn(II) ion were prepared using two general formulae: [Mn₂(H₂L₁)₂(L₂)₂X₄].4Cl (X = OH₂( 1 ), ONO₂⁻( 2 ), Cl=nil; OAc( 3 ), Cl = nil) and [Mn₂(H₂L₁)(L₂)₂(O₂SO₂)₂]( 4 ). Free ligands and their complexes were characterized. Electronic absorption spectra of the mixed-ligand complexes indicate a distorted octahedral geometry around the central metal ion, and the anions X⁻ are in the axial positions for all compounds. The ligands behave in a neutral bidentate manner, through nitrogen atoms and oxygen atoms of the carbonyl group (L₂), whereas H₂L₁ coordinated through nitrogen and OH groups as a neutral bidentate ligand. All complexes do not contain coordinated water molecules, but complex ( 1 ) contains four water molecules. The water molecules are removed in a single step. The complexes exhibited magnetic susceptibility corresponding to five unpaired electrons. The antimicrobial activity of the Mn(II) mixed-ligand complexes ( 1–4 ) against two gram-positive bacteria, three local gram-negative bacteria, and three fungi species was tested. Mn(II) mixed-ligand complex ( 2 ) exhibited significant antibacterial activity against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas sp. Mixed-ligand complex ( 2 ) exhibited a high potential cytotoxicity against the growth of human lung cancer cells.     

Synthesis,spectroscopy, electrochemistry,and methylation reaction of the dithiolate-based cobalt(II) complex derived from tert-butyl N-(2-mercaptoethyl)carbamate

A dithiolate-containing a carbamate mononuclear cobalt(II) complex namely, [Co(Boc-S)₂] (1), was obtained by the reaction of a methanolic solution of cobalt(II) nitrate hexahydrate with two equimolar amounts of the deprotonated form of tert-butyl N-(2-mercaptoethyl)carbamate (Boc-SH). The cobalt(II) complex (1) was characterized in the solid state and in solution by using FT–IR, Raman, UV–visible, and EI–mass spectroscopies, as well as thermal and X-ray diffraction studies. Spectral data showed that the carbamate (Boc-SH) acts as a mono-anionic bidentate ligand coordinating the cobalt(II) ion through two imine nitrogen and two deprotonated thiolate sulfur donor atoms in a distorted tetrahedral geometry. The thermoanalytical data evidence that the complex is stable up to 165 °C and undergoes complete decomposition, resulting in CoO. TEM imaging of the oxide residue shows its nano size clusters, suggesting that the complex (1) may be used as a precursor for nano-oxides. X-ray powder diffraction patterns evidence an isomorphism among the complex. The redox behavior of the cobalt(II) complex was also investigated by cyclic voltammetry. The reaction of the dithiolate cobalt(II) complex (1) with methyl iodide appears to occur intramolecularly with the cobalt-bound dithiolate, forming the cobalt(II)-bound dithioether complex [Co(Boc–SCH₃)₂]I₂ (2), as a dication complex with a clean second-order reaction of 13.24 × 10⁻² M⁻¹·s⁻¹.     

Identification of phytobioconstituents present in Simmondsia chinensis L. seeds extract by GC-MS analysis

Simmondsia chinensis L. commonly called as Jojoba and belongs to family Simmondsiaceae. It has shown positive pharmacological activities of these compounds which include antidiabetic, antirheumatic, anthelminthic, antipsoriatic, antioxidant, antiepileptic, antigonorrheal, analgesic, anti-inflammatory, and pesticidal activity of jojoba. The multifaceted action of numerous bioactives existing in the seed extract with therapeutic activity have attracted great research interest by pharmaceutical industries. n-hexane extract of Simmondsia chinensis L. (SC) Seeds was analysed by gas chromatography-mass spectroscopy for identification and characterization of phytobioconstituents and its therapeutic claim by traditional system. The major compounds discovered in SC seeds extract are cis-9-octadecen-1-ol (24.85%), 9-octadecen-1-ol, (Z)- (18.24%), Stigmast-5-en-3-ol (14.10%), Ergost-5-en-3-ol, (3-β)-ol (5.26%), (Z)-14-tricosenyl formate (5.24%), Thiositosteroldisulfide (3.64%), Silane, Dimethyl (dimethylpentyloxysilyloxy) tetradecyloxy- (3.41%), Ergost-5-ene, 3-methoxy-, (3β,24R)- (2.55%), Ergosta-5,22-dien-3-ol (2.22%), 1,19-eicosadiene (2.17%), Pentacosane (2.02%), Stigmasta-5,22-dien-3-ol (1.64%), 1,19-eicosadiene (1.57%), 9-octadecen-1-ol, (Z)- (1.46%), 9,19-cyclo-9β-lanostan-3β-ol, 24-methylene- (1.14%), (9Z)-9-octadecenyl palmitate (1.50%), Hexadecanoic acid, 9-octadecenyl ester, (Z) (1.37%), 9Z)-9-octadecenyl (9Z)-9-hexadecenoate (1.01%). The hexane extract of Simmondsia chinensis seeds comprises various polar and nonpolar phytobioconstituents. These compounds were established qualitatively via GC-MS evaluation. GC-MS reports will be promising in pharmaceutical sector in identification of variety of Phytobioconstituents in distinct plant extracts, polyherbal extract and the standardization of particular plant materials.     

Synthesis of 2,3-disubstituted pyrazines and quinoxalines by Heck cross-coupling reactions of 2,3-dichloropyrazine and 2,3-dichloroquinoxaline. Influence of the temperature on the product distribution

Heck cross-coupling reactions of 2,3-dichloropyrazine provide a convenient approach to 2,3-dialkenyl-, 2-alkenyl-3-alkyl-, and 2,3-dialkylpyrazines depending on the reaction conditions.     

Inhomogeneous magnetism in single crystalline Sr(3)CuIrO(6+delta): implications to phase-separation concepts

The single crystalline form of an insulator, Sr(3)CuIrO(6+delta), is shown to exhibit unexpectedly more than one magnetic transition (at 5 and 19 K) with spin-glass-like magnetic susceptibility behavior. On the basis of this finding, viz., inhomogeneous magnetism in a chemically homogeneous material, we propose that the idea of "phase separation" described for manganites is more widespread in different ways. The observed experimental features enable us to make a comparison with the predictions of a recent toy model on magnetic phase separation in an insulating environment.     

Remarks on Perturbation of Infinite Networks of Identical Resistors

The resistance between arbitrary sites of infinite square network of identical resistors is studied when the network is perturbed by removing two bonds from the perfect lattice. A connection is made between the resistance and the lattice Green’s function of the perturbed network. By solving Dyson’s equation the Green’s function and the resistance of the perturbed lattice are expressed in terms of those of the perfect lattice. Some numerical results are presented for an infinite square lattice.