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The reaction of β-ketosulfones with different α-functionalized nitroalkenes affords diversely substituted sulfonylfurans and dihydrofurans. Furthermore, β-ketosulfones react with α-bromonitroalkenes and α-hydrazinonitroalkenes via a cascade Michael addition-cyclization protocol to afford nitrodihydrofurans and hydrazinodihydrofurans, respectively, bearing a key sulfonyl group, in excellent yields with a broad substrate scope. Application of these products has been demonstrated by the synthesis of pyrroles and pyrazoles in good yields. The reaction of β-ketosulfones with nitroallylic acetates yields tetrasubstituted sulfonyl furans through a cascade S

Aedes aegypti is the main mosquito vector of dengue, zika, chikungunya, and yellow fever diseases. The low effectiveness of vector control options is mainly related to the increased insect's resistance and to the toxicity of products used for non-target organisms. The development of new environmentally friendly and safer products is imperative. Technical cashew nut shell liquid (tCNSL), mostly composed by cardanol (C), is an abundant by-product of the cashew (Anacardium occidentale L.) production chain, available at low cost, and with proven larvicidal activity. However, chemical modifications in both tCNSL and cardanol were required to increase their water solubilities. Our objectives were to synthesise and characterise sustainable, low-cost and easy-to-use multiple function products based on tCNSL, cardanol, and the sulphonates obtained from both; and to evaluate all these products efficacy as surfactants, larvicidal, and antimicrobial agents. None of the sulphonates presented antimicrobial and larvicidal activities. tCNSL and cardanol were successfully emulsified with sodium technical cashew nut shell liquid sulphonate (NatCNSLS, complex mixture of surfactants). The emulsions obtained presented larvicidal activity due to the presence of tCNSL and cardanol in their composition. Our results showed that the tCNSL+NatCNSLS mixture emulsion was an effective larvicide and surfactant multiple function product, with high availability and easy-to-use, which can facilitate its large-scale use in different environments. Graphical abstract.

A study of [3 + 2] cycloaddition reactions of a bicyclic nitrone with various cyclopentenes has clarified the diastereomeric preferences as a function of the olefinic structure. It has also identified an important stereochemical difference between nitrones and the analogous azomethine ylides in [3 + 2] cycloaddition reactions.

Organosulfur compounds show cytotoxic potential towards many tumor cell lines. Disulfides and thiosulfonates act through apoptotic processes, inducing proteins associated with apoptosis, endoplasmic reticulum stress, and the unfolded protein response. Three p-substituted symmetric diaryl disulfides and three diaryl thiosulfonates were synthesized and analyzed for inhibition of tubulin polymerization and for human cancer cell cytotoxic activity against seven tumor cell lines and a non-tumor cell line. S-(4-methoxyphenyl)-4-methoxybenzenesulfonothioate (6) exhibited inhibition of tubulin polymerization and showed the best antiproliferative potential, especially against the 786-0 cell line, being six times more selective as compared with the non-tumor cell line. In addition, compound 6 was able to activate caspase-3 after 24 and 48 h treatments of the 786-0 cell line and induced cell-cycle arrest in the G2/M stage at the highest concentration evaluated at 24 and 48 h. Compound 6 was able to cause complete inhibition of proliferation, inducing the death of 786-0 cells, by increasing the number of cells at G2/M and greater activation of caspase-3.

Acetylcholinesterase (AChEis) inhibitors are used to treat neurodegenerative diseases like Alzheimer's disease (AD). l-Hypaphorine (l-HYP) is a natural indole alkaloid that has been shown to have effects on the central nervous system (CNS). The goal of this research was to synthesize l-HYP and d-HYP and test their anticholinesterasic properties in rat brain regions. l-HYP suppressed acetylcholinesterase (AChE) activity only in the cerebellum, whereas d-HYP inhibited AChE activity in all CNS regions studied. No cytotoxic effect on normal human cells (HaCaT) was observed in the case of l-HYP and d-HYP although an increase in cell proliferation. Molecular modeling studies revealed that d-HYP and l-HYP have significant differences in their binding mode positions and interact stereospecifically with AChE's amino acid residues.

Inflammation is a natural response of the organism to an infection, trauma, or cellular stress. Pain is the first symptom of acute and chronic inflammation. The standard class of medication to treat inflammatory pain is the nonsteroidal anti-inflammatory drug (NSAID). These drugs are associated with severe side effects such as gastric ulcers, gastritis, or internal bleeding. One of NSAIDs, Dipyrone® (metamizole) is largely used in many European and South American countries despite its dubious effectivity and its withdrawal from the market of several countries. Here, aiming to identify a new anti-inflammatory drug prototype based on Dipyrone® structure, a set of 27 molecules were virtually screened, and 4 compounds containing the active metabolite 4-aminoantipyrine and 1,4-dioxo-2-butenyl fragment were selected for docking, synthesis, and biological evaluation. The selection was based on the number of H-bonds and π- π stacking interactions between the inhibitor and the amino acids within the binding site of the enzyme. Carrageenan-induced paw edema, acetic acid-induced writhing, and formalin assays were used to evaluate inflammation and pain response. The selected compounds 1-4 inhibited the involvement of biogenic amines in the formation of paw edema. Compounds 1-4 also reduced pain in the inflammatory response phase. It has to be noted that 4-AA may cause agranulocytosis, which should be borne in mind when developing drug candidates of similar structure. Our new drug prototypes based on 4-aminoantipyrine and 1,4-dioxo-2-butenyl moieties open a gate for developing a prototype of nonsteroidal anti-inflammatory drugs.

Cytosporones, a class of octaketide resorcinolic lipids, have drawn the attention of researchers for exhibiting a number of notable biological properties. Herein, we describe routes to synthesize the bioactive synthetic resorcinolic lipids AMS35AA and AMS35BB with excellent overall yields using 3,5-dimethoxybenzoic acid as the starting material. The methods proved remarkably efficient to achieve the target compounds and comprise the synthesis of AMS35AA catalyzed by ascorbic acid (vitamin C).

The amphyphylic triazoanilines recently synthesized 1-(4-(3-aminophenyl)-1H-1,2,3- triazole-1-yl)-3-(3-pentadecylphenoxy)propan-2-ol (1) and 1-(4-(4-aminophenyl)-1H- 1,2,3-triazole-1-yl)-3-(3-pentadecylphenoxy)propan-2-ol (2), synthesized from cardanol and glycerol, have photophysical properties which allow their use in the development of fluorescent biomarkers with applicability in the biodiesel quality control. Based on this, the present research evaluated the toxic effects of both compounds in different biological models through the investigation of survival and mortality percentages as a measure of acute toxicity on Daphnia similis and Oreochromis niloticus, larvicidal assay against Aedes aegypti, and cytotoxic activity on mammary cells. Results demonstrate that these triazoanilines 1 and 2 have shown low acute toxicity to the biological models investigated in this study up to the following concentrations: 4.0 mg L-1 (D. similis), 4.0 mg L-1 (A. aegypti larvae), 1.0 mg L-1 (O. niloticus), and 1.0 mg mL-1 (mammary cells). This fact suggests the potential for safe use of compounds 1 and 2 as fluorescent markers for the monitoring of biodiesel quality, even in the case of environmental exposure. Besides all of that, the reuse of cardanol and glycerol, both industrial wastes, favors the maintenance of environmental health and is in agreement with the assumptions of green chemistry. Graphical abstract ᅟ.

The formation of amide bonds is one of the most stimulating emerging areas in organic and medicinal chemistry. Amides are recognized as central building blocks in a plethora of interesting pharmaceuticals, proteins, peptides, polymers, natural products, functional materials, and biologically relevant carbocyclic or heterocyclic molecules, and they are also found in a variety of industrial fields. Therefore, a review of recent developments and challenges in the formation of amide bonds from carbonyl compounds is particularly important. Herein, we have scrutinized a range of metal-catalyzed and metal-free approaches for the synthesis of amides from aldehydes, ketones, and oximes. In addition, this Minireview highlights relevant mechanistic studies, as well as the potential applications of these methods in the synthesis of candidate drug molecules. We hope that the data compiled herein will encourage further progress in this notable area of chemistry research.

Cardanol was obtained by vacuum distillation of ‘‘cashew nut shell liquid’’ (CNSL). Cardanol is a by-product of cashew production and a building block for chemical synthesis; cardanol and its derivatives can be used for different types of applications. Three of these compounds are the subject of the present NMR study and theoretical comparison. 1H and 13C NMR signals were assigned using 1D and 2D NMR experiments. The DFT/B3LYP method using the cc-pVTZ basis set was employed for the calculations of the 1H and 13C NMR chemical shifts (δ). The obtained data were used as an auxiliary tool for unequivocal assignment of all 1H and 1³C NMR signals. For these compounds, the adopted theoretical model was sufficient to obtain a good description of the chemical shifts.

Aims Previous studies performed by our research group indicated that cytosporone analogues are capable of prevent or repair DNA damages. This work presents the evaluation of the activity of AMS35AA for metastatic murine melanoma cells (B16F10) in experimental model in vitro and, in pre-clinic assay of metastatic melanoma in vivo, using mice lineage C57BL/6. Main methods In vitro assays were performed: MTT and comet assay, flow cytometry evaluation, gene expression assay by RT-PCR, qualitative evaluation of cell death using B16F10 cells. In vivo assays: micronucleus and comet assay, splenic phagocytosis, melanoma murine model and histopathological analysis, using mice lineage C57BL/6 (n = 20). Key findings In vitro results performed by MTT assay showed that AMS35AA is cytotoxic for B16F10 cells (p Significance In summary, the study showed that AMS35AA reveals relevant results regarding to cytotoxicity of B16F10 murine melanoma cells, inducing death by apoptosis via mitochondrial and/or mediated by DNA damages.

This review addresses recent advances in fungal bioremediation of distinct pollutant aromatic amines (AAs) and their derivatives. AAs are toxic organic compounds used as intermediate for the production of several chemicals often released into the environment causing harmful impacts and health problems to humans and other animals. Although fungi proved successful in biotechnological approaches, including environmental decontamination, they still merit further attention. An efficient fungal bioremediation generates less-toxic, inert or fully degraded compounds. Thus, understanding degradation metabolic pathways of contaminants and their breakdown products is important to decide on the best methodology to employ in different polluted ecosystems.

Heavy consumption of non-renewable raw materials and/or renewable energy production produces environmental imbalance. Thus, the search for a means of sustainable and environmentally appropriate life requires scientific research in new renewable biofuels. The Calotropis procera, exotic oilseed widely distributed is a hardy shrub well suited to the northeast that produces seeds with oil. So, in this work were made fruit collection, drying, extraction and analysis of physical, chemical and thermal properties of oil aiming its use in biodiesel synthesis. The oil was extracted with Soxhlet method and characterized through physical-chemical, thermal analysis, and FTIR and NMR spectroscopy analysis. The results indicate that it is possible to obtain 21% ± 2 by weight of an oil physicochemical quality within the standard recommended by the legislation, except for the acid value was high and indicates that the best way to transesterification it is to make the catalyzed by acid or heterogeneous. The thermal analysis showed that the oil has high purity and is constituted by two material strips of different mass or molecular structures and has high thermal stability and convenient for the synthesis reaction. FTIR and NMR spectroscopy confirmed that the major compounds present in the oil are saturated and unsaturated fatty acids. DOI: http://dx.doi.org/10.17807/orbital.v10i2.1061

An efficient copper (I) halotriphenylphosphine catalyzed one-pot multicomponent reaction (MCR) of 3-substituted indole derivatives has been developed using a variety of aldehydes (aromatic, aliphatic, and heteroaromatic), indole, and active methylene substrates such as malononitrile and ethyl 2-cyano acetate. This reaction proceeds smoothly and obtained good to excellent yields (68–93%) using water as green solvent under ambient conditions. The obtained products were confirmed by 1H, 13C NMR, and mass spectroscopy techniques. The one-pot MCR occurs through formation of Knoevenagel adducts then followed by Michael addition of indole.

We report the synthesis and fluorescent properties of 1,4-disubstituted-1,2,3-triazoles (1a-c) based on pollutant wastes and by-products from the cashew and biodiesel industries as a design for fluorescent markers. The triazoles were synthesized in four steps; catalytic hydrogenation of cardanol, reaction with epichlorohydrin, azide substitution and/or epoxide opening and, Cu catalyzed click-chemistry of the azide with the ethynylanilines (6a-c). This procedure is a potential alternative to make fluorescent markers since it affords the intermediates in high yields, enabling one to produce the products in good quantities. Moreover, triazolazobenzenes (8a-c) were prepared by azo coupling of the trizoles (1a-c) with phenol to give a new option of dyes. Evaluation of the fluorescent properties of the achieved compounds showed that all triazole derivatives displayed good fluorescence emissions in the range of 325–400 nm, with a maximum of fluorescence intensity at around 350 nm when excited between 225 and 300 nm; besides, the para-triazolaniline exhibited a dual fluorescence emission, presenting an additional emission band in the blue range (400–500 nm).

Natural and synthetic sulfur-bearing organic compounds have many applications in medicinal chemistry. This article reports the preparation of amphiphilic β-hydroxy sulfides, sulfoxides, and sulfones derived from cardanol and glycerol. Thiolysis of cardanol epoxide 3 with various thiols (4a-4j) in ethanol or water yielded the corresponding β-hydroxy sulfides 5a-5j (61-95%). Treatment with 30% H2O2 in acetic acid at ambient temperature completely converted these products into β-hydroxy sulfoxides 6a-6j and sulfones 7a, 7c-7f, 7h-7j. The synthesized compounds were characterized by 1H nuclear magnetic resonance (NMR), 13C NMR, high-resolution mass spectroscopy (HRMS) and performed the in vitro evaluation antimicrobial activities against standard strains of Staphylococcus aureus and Escherichia coli. Compounds 5a, 5d-5f, and 5h-5j proved moderately active against S. aureus. None of the compounds were active against E. coli. β-Hydroxy-sulfides 5a-5j were also evaluated for antioxidant properties but failed to exhibit significant activity.

Chemotherapy for cancer treatment may result in a temporary or long-term gonadal damage resulting in subfertility or infertility. Cyclophosphamide (CY) is a cytotoxic alkylating agent that has been widely used in the treatment of cancer. Recent studies have shown that synthetic resorcinol lipid AMS35AA (3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one) may be an important adjuvant chemotherapy that potentiates mutagenic damage and increases apoptosis caused by CY. The present study investigates the action of AMS35AA alone or/in association with CY on testicular function. Animals were divided into four groups: (a) control group: received only water; (b) CY group: received 150 μg/g of CY b.w., i.p.; (c) AMS35AA group: received 10 μg/g of AMS35AA b.w., i.p; and (d) associated group: received 10 μg/g of AMS35AA + 150 μg/g of CY b.w., i.p. Four weeks after the treatment, the results showed that testes weight of CY and associated groups decreased. However, the number of Sertoli cell and Leydig cell per testis was similar in control and treated groups. Our findings provide strong evidence that the AMS35AA alone or in CY association is not toxic to spermatogenesis. The absence of toxicity of AMS35AA supports the view that the resorcinolic lipid could be used associated with CY chemotherapy without causing adverse effects to testes function.

The cashew plant (Anacardium occidentale L.) is the source of a wide variety of bioactive compounds consisting of phenolic lipids, mainly present in the spongy shells of cashew nuts. The liquid in the cashew nut shell generated after nut roasting in the food industry, which is usually treated as waste. However, it contains high amount of cardanol that could be used as a building block and are of innumerable applications. Herein, we report the synthesis of eleven 1,4-disubstituted 1,2,3-triazoles, derived from the cardanol, in an environmentally non-egregious fashion, and a cytotoxic evaluation study using the MCF-7 (breast carcinoma), 786-0 (kidney carcinoma) and HT-29 (colon carcinoma) cancer cell lines and cytotoxic evaluations against Trypanosoma cruzi. Five of the eleven triazoles presented high toxicity against the 786-0 kidney cancer cell line. However, no relevant toxicity to the T. cruzi amastigote was observed when compared with benznidazole (standard drug). A cell viability study demonstrated that these compounds act over a broad range of concentrations, which implies that they may be applied even in low doses. These results indicate an alternative use of cardanol in greener synthesis of potent anticancer drug candidates.

Neem, Azadirachta indica A. Juss, is endowed with relevant biological properties and its oil contains unsaturated fatty acids that are susceptible to structural modification by oxidative processes such as ozonolysis to form peroxides. Therefore, the aim of this work was the synthesis, physicochemical characterization, study of thermal behavior, and evaluation of the antimicrobial potential of neem ozonated oils. The ozonolysis reaction was performed over different periods of time, in the presence or absence of water at an ozone concentration of 63 mg L−1 O3/O2. The samples were characterized by 1H and 13C NMR spectroscopy, acid and iodine values and, DSC and TG/DTG thermal analyses. Additionally, quantitative 1H NMR spectroscopy was a very successful and useful tool to determine the unsaturation degree of samples. The products showed excellent broad-spectrum antimicrobial activity in comparison to other ozonated oils reported in the literature, with an MIC of

The analgesic drug dipyrone is used to treat side effects (including pain and fever) of cancer chemotherapeutic agents. Dipyrone is metabolized to 4-aminoantipyrine (4-AA), a PGE2-dependent blocker and inhibitor of cyclooxygenase (COX). We evaluated the genotoxic, mutagenic, apoptotic, and immunomodulatory activities of 4-AA in vivo and the effects of its combination with the antineoplastic drugs doxorubicin, cisplatin, and cyclophosphamide. 4-AA did not cause genotoxic/mutagenic damage, splenic phagocytosis, or leukocyte alterations. However, when combined with the antineoplastic agents, 4-AA decreased their genotoxic, mutagenic, apoptotic, and phagocytic effects. These results suggest that 4-AA might interfere with DNA damage-mediated chemotherapy.

Diaryl disulfides and diaryl thiosulfonates were synthesized with the two phenyl rings of all compounds bearing identical halide substituents. Because of structural similarity to the potent antimitotic natural product combretastatin A-4 (CA-4), the compounds were examined for inhibition of tubulin polymerization, and the thiosulfonates were more active than the disulfides. The nine thiosulfonates had IC50 values ranging from 1.2 to 9.1 µM, as compared with 1.3 µM obtained with CA-4. The compounds thus ranged from equipotent with CA-4 to 7-fold less active. The nine disulfides had IC50 values ranging from 1.2 to 5.1 µM, as compared with 0.54 µM obtained with CA-4. The compounds thus ranged from less than half as active as CA-4 to over 9-fold less active. The most active members of each group, 2 g and 3c, in the assembly assay were modeled into the colchicine site. Compound 3c had significant hydrophobic interactions with β-tubulin residues CYS 241 and ALA 250, and its thiosulfonate bridge made a hydrogen bond with β-tubulin residue ASN 258. Compound 2 g had hydrophobic interactions with β-tubulin residues ALA 250, CYS 241 and ALA 254, but there was no significant interaction of the disulfide bridge with tubulin.

Background/aim In recent years, the search for new anticancer experimental agents derived from natural products or synthetic analogues, such as resorcinolic lipids, has received increased attention. The present study aimed to evaluate the antitumor potential, describe the cell death mechanism and the effects of 3-Heptyl-3,4,6-trimethoxy-3Hisobenzofuran-1-one (AMS35AA) in combination with different chemotherapeutic agents in the MCF-7 cell line. Materials and methods Analysis of cytotoxic, genotoxic, membrane integrity, cell death and gene expression induced by the compound was performed. Results The AMS35AA and its association with 5-FU demonstrated reduction of cell viability; increase of cell death; enhancement of genomic damage and accumulation of cells in G2/M phase. Conclusion AMS35AA has potential for breast cancer treatment since it is capable of exerting cytotoxic and cytostatic effects in a breast cell line and also could be an adjuvant in cancer therapy when combined with 5-FU.

The increased incidence of cancer and its high treatment costs have encouraged the search for new compounds to be used in adjuvant therapies for this disease. This study discloses the synthesis of (Z)-4-((1,5-dimethyl-3-oxo-2-phenyl-2,3dihydro-1H-pyrazol-4-yl) amino)-4-oxobut-2-enoic acid (IR-01) and evaluates not only the action of this compound on genetic integrity, increase in splenic phagocytosis and induction of cell death but also its effects in combination with the commercial chemotherapeutic agents doxorubicin, cisplatin and cyclophosphamide. IR-01 was designed and synthesized based on two multifunctionalyzed structural fragments: 4-aminoantipyrine, an active dipyrone metabolite, described as an antioxidant and anti-inflammatory agent; and the pharmacophore fragment 1,4-dioxo-2-butenyl, a cytotoxic agent. The results indicated that IR-01 is an effective chemoprotector because it can prevent clastogenic and/or aneugenic damage, has good potential to prevent genomic damage, can increase splenic phagocytosis and lymphocyte frequency and induces cell death. However, its use as an adjuvant in combination with chemotherapy is discouraged since IR-01 interferes in the effectiveness of the tested chemotherapeutic agents. This is a pioneer study as it demonstrates the chemopreventive effects of IR-01, which may be associated with the higher antioxidant activity of the precursor structure of 4-aminoantipyrine over the effects of the 1,4-dioxo-2-butenyl fragment.

Este trabalho relata a extração atraves dois métodos (a frio e a quente), com solventes orgânicos o material lipídico obtido das vísceras da Sardinella Brasiliensis. Os lipidios foram submetidos a uma hidroesterificação utilizando iodo sublimado como catalisador. O óleo e o biodiesel foram caracterizados por RMN H1, espectroscopia FTIR, tensão superficial, densidade e água e sedimentos. Os resultados de água e sedimentos e densidade foram comparados com os previstos na legislação. Os resultados evidenciaram que o método à frio forneceu melhor rendimento na extração do óleo, que ocorreu a hidroesterificação do material indicado na técnica de RMN H1 pelos dois prótons com sinal de quarteto na região de 4,2 ppm referentes aos hidrogênios metilênicos (CH2 ɑ-O), característicos de mono ésteres etílicos (biodiesel) e na técnica de FTIR pelo aparecimento de deformações axiais características de ésteres em 1.742 cm-1. Assim concluiu-se que as vísceras da sardinha são uma matéria-prima promissora e barata para produção de biodiesel, no entanto há necessidade de melhor caracterização da sua qualidade físico-química e estabilidade.

Herein, we report the synthesis of 12 new naphthoquinone derivatives, 6 substituted 1,4-naphthoquinones and 6 heterocycle-fused naphthoquinones, as well as evaluation of their trypanocidal and leishmanicidal activities. Compounds 11a and 13a were active against the amastigote stage of T. cruzi and showed low cytotoxic effects. With respect to leishmanicidal assays, all compounds were inactive against the promastigote stages of L. chagasi and L. braziliensis.

In this work, we have synthesized ozonides from sunflower, flaxseed and baru oils. In addition, ozonolysis reaction of sunflower oil in the presence of water was performed, and the product obtained had high viscosity and a gel-like appearance. The ozonated products were investigated for their antimicrobial activity and cytotoxicity. The oleogel, with an MIC ≤ 3 mg mL−1, exhibited excellent antimicrobial activity against standard and clinical strains. All products showed no cytotoxicity when tested against NIH/3T3 murine fibroblast cells. Effects of ozonation time on the oils were analyzed by IR, 1H and 13C NMR spectroscopy. DSC analysis shows that the ozonides of vegetable oils decompose with a peak at about 150 °C and with a broad exotherm. The decomposition enthalpy is proportional to the degree of ozonation reached.

Octocrylene (2-ethylhexyl 2-cyano-3,3-diphenyl-2-propenoate) is present in several sunscreens and is known to work synergistically with UV filters. We prepared eight octocrylene-related compounds to test their photoprotective activities by measuring diffuse transmittance. The compounds had varied photoprotection profiles, with Sun Protection Factors (SPF) ranging from 1 to 5 and UVA Protection Factors (UVAPF) ranging from 1 to 8. Compounds 4, 5, and 7 showed the best protection against UVB sunrays, while compounds 5, 6, and 7 presented the best results for protection from UVA, so compound 7 had the most balanced protection overall. Results for compounds 4, 8, and 9 are reported for the first time in the literature.

Resorcinolic lipids have important biological actions, including anti-carcinogenic activity. Therefore, we evaluated the mutagenic, genotoxic, immunomodulatory and apoptotic potential and the biochemical and histopathological changes caused by the synthetic resorcinolic lipid 3-Heptyl-3,4,6-trimethoxy-3H-isobenzofuran-1-one, (AMS35AA; 10, 20 and 40 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg) in Swiss mice. The results indicated that AMS35AA is not genotoxic or mutagenic and does not alter liver or kidney histology. However, the compound does cause an increase (p < 0.05) in the levels of glutamic-oxaloacetic transaminase and creatinine and in splenic phagocytosis and liver and kidney apoptosis. When combined with cyclophosphamide, AMS35AA caused increased (p < 0.05) mutagenic damage (although the compound had anti-genotoxic activity), splenic phagocytosis, neutropenia and glutamic-oxaloacetic transaminase and creatinine levels (even in the absence of histological damage) and induced liver and kidney apoptosis. We conclude that this resorcinolic lipid may be an important chemotherapy adjuvant that can potentiate mutagenic damage and increase apoptosis caused by cyclophosphamide without causing adverse effects. In addition, the immunomodulatory activity of the compound should be noted, which counters reductions in lymphocyte number, a primary side effect of cyclophosphamide in cancer therapy.

A method is described for the synthesis of (±)-2,3-epoxy propyl esters from glycerol, involving reaction of epichlorohydrin with sodium or potassium salts of carboxylic acids in the presence of TBAB as catalyst, with moderate to excellent yields. Kinetic resolution of glycidyl butyrate by lipase of Thermomyces lanuginosa has been achieved with remarkable enantiomeric excess (ee >99%) using 1,4-dioxane as a co-solvent in pure buffer solution (30 and 50 °C, pH = 7.0).

This Letter introduces a new, cheap and green protocol for the thio-Michael reaction. Here we applied three free enzymes such as lipase from pancreas porcine, chymosin and papain and an immobilized one: the Liposyme®. The reactions were executed at room temperature and resulted in the thio-Michael adduct in good or excellent yields. The protocol describes the use of EtOH as solvent and a less percentage of enzymes, which is in concordance with the green chemistry topics, so we can mention that chymosin and papain were used as biocatalyst in an organic reaction for the first time in this Letter.

(4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) is a known cytotoxic compound belonging to the phenstatin family. However, the exact mechanism of action of PHT-induced cell death remains to be determined. The aim of this study was to investigate the mechanisms underlying PHT-induced cytotoxicity. We found that PHT displayed potent cytotoxicity in different tumor cell lines, showing IC50 values in the nanomolar range. Cell cycle arrest in G2/M phase along with the augmented metaphase cells was found. Cells treated with PHT also showed typical hallmarks of apoptosis such as cell shrinkage, chromatin condensation, phosphatidylserine exposure, increase of the caspase 3/7 and 8 activation, loss of mitochondrial membrane potential, and internucleosomal DNA fragmentation without affecting membrane integrity. Studies conducted with isolated tubulin and docking models confirmed that PHT binds to the colchicine site and interferes in the polymerization of microtubules. These results demonstrated that PHT inhibits tubulin polymerization, arrests cancer cells in G2/M phase of the cell cycle, and induces their apoptosis, exhibiting promising anticancer therapeutic potential.

A new dihydropyranexanthone derived from the natural xanthone lichexanthone (1) was synthesised and, together with other 18 derivatives including ω-bromo and ω-aminoalkoxylxanthones (containing methyl, ethyl, propyl, tertbutylamino and piperidinyl moieties), were tested against Mycobacterium tuberculosis. Nine ω-aminoalkoxylxanthones showed good antimycobacterial activity, and their in vitro cytotoxicity was determined using VERO cells in order to calculate the selectivity index (SI). One of these nitrogenated xanthone derivatives showed very promising results, with MIC of 2.6 μM and SI of 48. This MIC is comparable to values found in "first and second line" drugs commonly used to treat TB. In order to understand better about this compound, it was evaluated together with two other ones that showed good SI, against resistant clinical strains of M. tuberculosis to verify the existence of cross-resistance. A chemometrical approach was useful to establish a pattern of antitubercular activity among the group of ω-aminoalkoxylxanthones, according to some structural and chemical features.

Made available in DSpace on 2018-11-29T06:20:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-03-01. Added 1 bitstream(s) on 2019-10-09T18:25:56Z : No. of bitstreams: 1 S0103-50532018000300639.pdf: 347454 bytes, checksum: 0e8bf43c43cd9b732cb0cc1b7921b7cd (MD5) FUNDECT (PRONEM) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Kardol Ind. Quimica Ltda. The synthesis of novel amino alcohol derivatives based on cardanol and glycerol were achieved in good yields and characterized by H-1 and C-13 NMR (nuclear magnetic resonance) and MS (mass spectrometry). In addition, we evaluated the in vitro antimicrobial activity against Gram-positive (Staphylococcus aureus, standard and clinical strains), Gram-negative (Escherichia coli) and M. tuberculosis bacterial strains. The bioassay results indicated that four compounds showed activity against S. aureus, including the clinical resistant strain, with MIC (minimum inhibitory concentration) ranging from 3.90 to 15.60 mu g mL(-1) and M. tuberculosis, with MIC90 (minimum inhibitory concentration required to inhibit the growth of 90% of organisms) ranging from 3.18 to 7.36 mu g mL(-1). Univ Fed Mato Grosso Do Sul, Inst Quim INQUI, Av Senador Felinto Muller 1555, BR-79074460 Campo Grande, MS, Brazil Univ Fed Espirito Santo, Dept Quim, BR-29075910 Vitoria, ES, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, Brazil Univ Fed Mato Grosso Do Sul, Inst Biociencias INBIO, Cidade Univ S-N,CP 549, BR-79070900 Campo Grande, MS, Brazil Univ Estadual Paulista, Fac Ciencias Farmaceut, BR-14801902 Araraquara, SP, Brazil FUNDECT (PRONEM): 054/12

Derived from ozonetherapy, the ozonized oils represent an Ozonized oils represent an interesting pharmaceutical approach to the management of a variety of dermatological pathologies. Ozone reacts with carbon-carbon double bonds of unsaturated fatty acids according to the mechanism described by Criegee, forming ozonides or 1,2,4 trioxolane rings and peroxides as the most important products, responsible for the antimicrobial activity and stimulating tissue repair and regeneration properties. The ozonized vegetable oils can be liquids or semisolids at room temperature and have stability periods that may be adequate for commercial distribuition. Ozonized sunflower oil (Oleozon®), a drug registered nationally and developed in the Ozone Research Center in Cuba has been tested and it was found to have valuable antimicrobial activity against bacteria, fungi and virus. FT-IR and NMR technics are used to confirm the structural changes undergone by oil during the ozonation. For determining the quality of ozonized oils, analytical methods such as peroxide, acidity and iodine values are usually carried out. Products are available for an alternative use of available resources, natural and renewable sources, simple technology, low cost and with extensive biological activity with reduced collateral effects. DOI: http://dx.doi.org/10.17807/orbital.v4i4.467

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).

A revista cientifica Orbital: The Electronic Journal of Chemistry foi criada por professores da Universidade Federal de Mato Grosso do Sul em 2008, visando a publicacao de artigos originais em todas as areas da quimica e suas interfaces com a farmacia, biologia e fisica. A missao da Orbital e de ser uma revista cientifica de Quimica, totalmente eletronica e com acesso livre e irrestrito e sem nenhuma taxa, tanto para o autor como para o leitor. A revista tem periodicidade trimestral e publica edicoes tematicas tambem. Os artigos sao submetidos a processo de revisao por pares. Teve seu primeiro nimero lancado em 2009. Desde 2015 possui atribuicoes do DOI e esta indexada em diversas bases de dados, incluindo ESCI (Web of Science), DOAJ, CAS, EBSCO, Google Scholar, Latindex, dentre outros. Neste trabalho, estamos apresentando um historico do processo de criacao e tambem uma analise do perfil da revista do periodo de 2009 a 2016.

Cardanol is an effective antioxidant and is a compound with antimutagenic and antitumoral activity. Here, we evaluated the genotoxic and mutagenic potential of saturated side chain cardanol and its effects in combination with cyclophosphamide in preventing DNA damage, apoptosis, and immunomodulation. Swiss mice were treated with cardanol (2.5, 5 and 10 mg/kg) alone or in combination with cyclophosphamide (100 mg/kg). The results showed that cardanol is an effective chemopreventive compound, with damage reduction percentages that ranged from 18.9 to 31.76% in the comet assay and from 45 to 97% in the micronucleus assay. Moreover, cardanol has the ability to reduce the frequency of apoptosis induced by cyclophosphamide. The compound did not show immunomodulatory activity. A final interpretation of the data showed that, despite its chemoprotective capacity, cardanol has a tendency to induce DNA damage. Hence, caution is needed if this compound is used as a chemopreventive agent. Also, this compound is likely not suitable as an adjuvant in chemotherapy treatments that use cyclophosphamide.

GIAO model at DFT/B3LYP level of theory using the cc-pVTZ basis set was employed for calculations of 1H and 13C NMR chemical shifts (δ) for various rigid polycyclic compounds. The data obtained were used as an auxiliary tool to an unequivocal assignment of all 1H and 13C NMR signals and the endo/exo stereochemistry of the strained compounds studied. For these compounds the theoretical model adopted was sufficient to obtain a good description of chemical shifts.

A series of 15 ω-aminoalkoxylxanthones containing methyl, ethyl, propyl, tert-butylamino and piperidinyl moieties were synthesized from a natural xanthone isolated from a lichen species. These compounds were tested for their in vitro antibacterial properties against Gram-positive and Gram-negative bacteria and cytotoxicity against a number of human tumor cell lines was too evaluated. The newly synthesized derivatives revealed selective activity against Staphylococcus aureus (Gram-positive), and the most promising results are for a multidrug resistant strain, for which six of these compounds showed good activity (MICs 4 µg/mL). Many derivatives inhibited tumor cells growth and most compounds were active on multiple lines.

The direct E/Z configuration assignment of tri- and tetra-substituted stilbenes (and other analogous olefins) when only one of the isomers is available is a quite challenging task. Sometimes, a chemical transformation or some other tedious method is necessary for determination of the double bond substitution pattern. In this paper, we relied on theoretical calculation of chemical shifts as a complementary tool for 1H NMR determination of the configuration of an α-phenylcinnamic acid prepared as a unique isomer by the Perkin reaction.

Bioactive cage-like polycyclic compounds have attracted the attention of several research groups because of their unique appearance and their biological activities. Their structures were established on the basis of (1)H NMR and (13)C NMR spectroscopic data. The (1)H and (13)C signal assignments and most homonuclear hydrogen coupling constants were assigned by use of techniques such as 1D (1)H and (13)C NMR and 2D gCOSY, non-edited gHSQC and gHMBC. The gNOESY experiments proved the endo-stereochemistry.

The present study aimed to evaluate the ability for biotransformation of the Diels-Alder adduct tricyclo[6.2.1.02,7]undeca-4,9-dien-3,6-dione (1) and two synthetic derivatives by the saprobe fungus Mucor ramosissimus Samutsevitsch. Products from oxidation, isomerization and, regioselective and enantioselective reduction were achieved. Neste trabalho avaliou-se a capacidade de biotransformação do aduto de Diels-Alder triciclo[6.2.1.02-7]undeca-4,9-dien-3,6-diona (1) e dois derivados sintéticos pelo fungo sapróbio Mucor ramosissimus Samutsevitsch. Produtos de oxidação, isomerização e redução regiosseletiva e enantiosseletiva foram obtidos.

Studies examining various spacer groups that link the two aromatic rings of combretastatin A-4 (CA4) have shown that the biological activity of analogs does not require the cis-stilbene configuration of CA4. Oxygen or nitrogen, carbonyl, methylene and ethylene spacers, for example, are present in CA4 analogs that show good activity. Up to now sulfur was not tested for this purpose. In this article we describe the synthesis of sulfide, sulfoxide and sulfone spacers between two aromatic rings comparable to those of CA4. We also compared them with CA4 for inhibitory effects on cell growth, tubulin polymerization, and the binding of [(3)H]colchicine to tubulin. We found that the sulfide is highly active and may be a lead compound for the preparation of antitumor compounds.