Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

Synthesis and multi-target biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents

We have synthesized a family of rhein-huprine hybrids to hit several key targets for Alzheimer"s disease. Biological screening performed in vitro and in Escherichia coli cells has shown that these hybrids exhibit potent inhibitory activities against human acetylcholinesterase butyrylcholinesterase, and BACE-1, dual Aβ42 and tau anti-aggregating activity, and brain permeability. Ex vivo studies with the leads (+)- and (-)-7e in brain slices of C57bl6 mice have revealed that they efficiently protect against the Aβ-induced synaptic dysfunction , preventing the loss of synaptic proteins and/or have a positive effect on the induction of long term potentiation. In vivo studies in APP-PS1 transgenic mice treated i.p. for 4 weeks with (+)- and (-)-7e have shown a central soluble Aβ lowering effect, accompanied by an increase in the levels of mature amyloid precursor protein (APP). Thus, (+)- and (-)-7e emerge as very promising disease-modifying anti-Alzheimer drug candidates.

Volatile constituents of the oils from Povedadaphne Quadriporata (lauraceae) from "Alberto M. Brenes" biological preserve, Costa Rica

The composition of the leaf, bark and wood oils of Povedadaphne quadriporata W. Burger from Costa Rica were analyzed by capillary GC/FID and GC/MS. One hundred and sixty-three compounds were identified. The major components from the leaf oil were a-pinene (21.2%), germacrene D (18.1%), b-pinene (14.8%), a-phellandrene (7.8%), a-copaene (6.6%), b-caryophyllene (6.1%) and d-cadinene (3.5%). From bark oil, the main constituents were a-pinene (27.7%), p-cymene (7.8%), b-pinene (7.4%), camphene (3.6%), a-copaene (3.5%) and limonene (3.3%). From wood oil, 1,10-di-epi-cubenol (8.0%), a-eudesmol (3.4%), cadalene (3.4%) and d-cadinene (3.0%) were the major compounds identified. This paper describes for the first time the composition of essential oils in this unique species and genus.

Natural occurrence, biological activities and synthesis of eight-, nine-, and eleven-membered ring lactones

The natural occurrence, biological activities and synthetic approaches to natural eight-, nine-, and eleven-membered lactones is reviewed. These medium ring lactones are grouped according to ring size, and their syntheses are discussed. The structures of some natural products early identified as medium-ring lactones were revised after total synthesis.

Lychnophorinae (asteraceae): a survey of its chemical constituents and biological activities

This work reviews the current literature about the chemical constituents and the biological activities of the subtribe Lychnophorinae (Vernonieae, Asteraceae). The notable secondary metabolites are sesquiterpene lactones of furanoheliangolide (goyazensolide and eremantholide types) and flavonoids. Some of its most investigated activities include its anti-inflammatory, analgesic, antimicrobial and cytotoxic activities, specially for the Lychnophora and Eremanthus species. The data presented on this paper not only displayed the role played by the Lychnophorinae species as a source of bioactive compounds, but also reinforced the need of further studies involving the species of such subtribe.

Synthesis and biological activity of n-{5-(4-methylphenyl) diazenyl-4-phenyl-1, 3-thiazol-2-yl}benzamide derivatives

In the present study, various amides of 2-amino-5-(4-methylphenyl)-diazenyl-4-phenyl-1, 3-thiazole was synthesized and their biological activities were evaluated. All the synthesized compounds were characterized by the combination of elemental analysis and standard spectroscopic methods. They are screened for anti-bacterial activity against Escherichia coli and Staphylococcus aureus as well as screened for antifungal activity against Aspergillus niger and Apergillus oryzae by cup plate method at 1 µg/ mL concentration in DMF.

Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance

A new series of 3-chloro-1-{[2-(6-nitro-1H-indazol-1-yl)ethyl]amino}-4-(substituted phenyl)-2-azetidinones (4a-j) was synthesized in four steps from 6-nitro-1H-indazole and characterized by IR, ¹H NMR, 13C NMR, FAB-mass spectrometry and chemical methods. Compounds 4(a-j) were screened in vitro for their antibacterial, antifungal and antitubercular activities against some selected microorganism and for their antiinflammatory activity (in vivo) against albino rats (either sex). All above activities of compounds 4(a-j) showed acceptable results.

Synthesis and biological evaluation of biaryl analogs of antitubulin compounds

This paper reports the synthesis of methanones and esters bearing different substitution patterns as spacer groups between aromatic rings. This series of compounds can be considered phenstatin analogs. Two of the newly synthesized compounds, 5a and 5c, strongly inhibited tubulin polymerization and the binding of [³H] colchicine to tubulin, suggesting that, akin to phenstatin and combretastatin A-4, they can bind to tubulin at the colchicine site.

Occurrence, biological activities and 13C NMR data of amides from Piper (Piperaceae)

This manuscript describes an update review with up to 285 references concerning the occurrence of amides from a variety of species of the genus Piper (Piperaceae). Besides addressing occurrence, this review also describes the biological activities attributed to extracts and pure compounds, a compiled 13C NMR data set, the main correlations between structural and NMR spectroscopic data of these compounds, and employment of hyphened techniques such as LC-MS, GC-MS and NMR for analysis of amides from biological samples and crude Piper extracts.

Synthesis and biological activity of sulfur compounds showing structural analogy with combretastatin A-4

We extended our previous exploration of sulfur bridges as bioisosteric replacements for atoms forming the bridge between the aromatic rings of combretastatin A-4. Employing coupling reactions between 5-iodo-1,2,3-trimethoxybenzene and substituted thiols, followed by oxidation to sulfones with m-CPBA, different locations for attaching the sulfur atom to ring A through the synthesis of nine compounds were examined. Antitubulin activity was performed with electrophoretically homogenous bovine brain tubulin, and activity occurred with the 1,2,3-trimethoxy-4-[(4-methoxyphenyl)thio]benzene (12), while the other compounds were inactive. The compounds were also tested for leishmanicidal activity using promastigote forms of Leishmania braziliensis (MHOM/BR175/M2904), and the greatest activity was observed with 1,2,3-trimethoxy-4-(phenylthio)benzene (10) and 1,2,3-trimethoxy-4-[(4-methoxyphenyl) sulfinyl]benzene (15).

Synthesis, characterization, and biological activity of a new class of dialkylphosphorylhydrazone derivatives of isatin

Sixteen dialkylphosphorylhydrazones were synthesized by condensation of phosphorylhydrazines with substituted isatins. Products were characterized by FTIR, ¹H-NMR, 13C-NMR, and 31P-NMR. Fungicidal activities of these compounds against Rhizoctonia solani and Fusarium oxysporum were also evaluated. Some compounds inhibited the growth of Rhizoctonia solani and Fusarium oxysporum by 43% and 51%, respectively. These compounds exhibited no effects on germination of lettuce seeds (Lactuca sativa L).

SYNTHESIS AND BIOLOGICAL EVALUATION OF SPIRO[INDOLINE-3,4’-PYRANO[2,3-C:6,5-C’]DIPYRAZOL]- 2-ONES IN THE PRESENCE OF SBA-Pr-SO3H AS A NANOCATALYST

Sulfonic acid functionalized SBA-15 nanoporous material (SBA-Pr-SO3H) with a large pore size of 6 nm, a high surface area, high selectivity, and excellent chemical and thermal stability was applied as an efficient heterogeneous nanoporous acid catalyst in the reaction of isatin with pyrazolones under mild reaction conditions. A novel class of symmetrical spiro[indoline-3,4'-pyrano[2,3-c:6,5-c']dipyrazol]-2-one derivatives was successfully obtained in high yields. Comparison of these results with those reported in the literature shows that the current method is efficient, and results in better reaction times and yields of the desired products. Other advantages of this new method are its operational simplicity, easy work-up procedure, and the use of SBA-Pr-SO3H as a reusable and environmentally benign nanoreactor, such that the reaction proceeds easily in its nanopores. We also tested the antimicrobial activity of the prepared compounds using the disc diffusion method, and some of the synthesized compounds exhibited the best results against B. subtilis and S. aureus.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF NEW SERIES OF ORGANOTIN(IV) ESTERS WITH N,N-DIACETYLGLYCINE

A bioactive N,N-diacetylglycine (NNDAG) and new organotin(IV) complexes (OTCs) (1-7) were synthesized. Spectroscopic techniques were employed to characterize NNDAG and OTCs. FTIR was employed to verify N,N protection of glycine by acetyl groups. The disappearance of υ(OH) at 3000-2600 cm-1 showed de-protonation of free ligand. The Δυ 150<200 cm-1 of OTCs 4-7 verified bidentate coordination with tetrahedral geometry. The Δυ of OTCs1 and 3 was <200 cm-1 exhibitingtrans -octahedral geometry while OTC 2 dimer was assigned a unique sinusoidal view. The 1H NMR spectra of OTCs verified their synthesis by de-protonation of NNDAG and no chemical shift was found downfield for carboxylic acid proton. The 13C, 119Sn NMR and Mass spectrometric data also supported FTIR and 1H NMR descriptions. The OTCs 4, 5, 6 and7 (500 ppm) proved twice as active against Escherichia coli as the standard antibiotic enoxacin (1000 ppm). The promising property of the OTCs (4, 5, 6 and7) is clearly due to their tetrahedral. The OTCs 4and 5 exhibited excellent activity against M. minimum and good activity against T. castaneum.LD50 of all the compounds were determined and OTCs4, 5 and 7 were found to be active.

Biological and molecular characterization of an isolate of Tobacco streak virus obtained from soybeans in Brazil

A virus was isolated from soybean (Glycine max) plants with symptoms of dwarfing and bud blight in Wenceslau Braz County, Paraná, Brazil. The host range and properties resembled those of Tobacco streak virus (TSV). The purified virus showed three peaks in a frozen sucrose gradient. Antiserum was produced and the virus was serologically related to TSV. Electron microscopy detected 28 nm spherical particles. Coat protein (CP) had a Mr of 29.880 Da. A fragment of 1028 nt was amplified, cloned and sequenced. One open reading frame with 717 nt was identified and associated to the CP. The CP gene shared 83% identity with the sequence of TSV CP from white clover (Trifolium repens) (GenBank CAA25133). This is the first report of the biological and molecular characterization of TSV isolated from soybeans. It is proposed that this isolate be considered a strain of TSV named TSV-BR.