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Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of

Several valuable biologically active molecules can be obtained through C–H activation processes. However, the use of expensive and not readily accessible catalysts complicates the process of pharmacological application of these compounds. A plausible way to overcome this issue is developing and using cheaper, more accessible, and equally effective catalysts. First-row transition (3d) metals have shown to be important catalysts in this matter. This review summarizes the use of 3d metal catalysts in C–H activation processes to obtain potentially (or proved) biologically active compounds.

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.

This study aimed to investigate the concordance of different nutritional assessment methods and the prevalence of inadequate nutritional status in newly diagnosed Colorectal cancer (CRC) patients. Cross sectional study was conducted in a public hospital in Alagoas, Brazil. Clinical, nutritional (patient-generated subjective global assessment [PG-SGA], body mass index [BMI], arm circumference [AC], triceps skinfold [TSF], arm muscle circumference [AMC]) and functional (handgrip strength [HGS]) data were collected from July 2017-January 2019. Of the 31 CRC patients with a mean age of 58.97 ± 14.96 years, 48.4% were elderly and 51.6% were female. TSF adequacy (80.8%) and PG-SGA (80.0%) revealed the highest prevalence of malnutrition. BMI identified the same prevalence of malnutrition and excess weight (30.0%). The concordance between PG-SGA and BMI (kappa = 0.086; p = 0.426) was slight, with fair HGS (kappa = 0.268; p = 0.124). PG-SGA and AC (kappa = 0.015; p = 0.99), TSF (kappa = 0.195; p = 0.558) and AMC adequacy (kappa = 0.142; p = 0.380) were poor. PG-SGA can diagnose malnutrition, even in those who are eutrophic/overweight, by other methods. Various methods do not show concordance with PG-SGA, confirming the need for both objective and subjective methods for better diagnosis of CRC patients.

The current manuscript describes the catalysts in click chemistry reactions, mechanism insights and use of other metals beyond copper associated with Azide-Alkyne Cycloadditions (AAC). Due to their biological importance and several applications in various areas of science, significant efforts have been devoted to devise robust methods for the synthesis of triazoles. Among these approaches, azide-alkyne cycloadditions strategy has been consolidated as a powerful tool for preparing this class of heterocycles. Herein, click reactions involving catalysis with metals other than copper are presented and critically discussed.

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).

International audience; A heterogeneous catalyst was assembled with ruthenium nanoparticles on carbon nanotubes and used in a mild oxidation method to prepare sulfones from sulfides. The system proved very efficient on the investigated substrates and the products were obtained in high yields.

Diverse examples are provided of enantioselective sequences for the transformation of cycloalkenes to either chiral trans-β-substituted cycloalkanols or chiral α-amino ketones.

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.

The comparison in several reaction conditions for synthesis of nonracemic α-methylsulfinylation of 3,4-dihydronaphthalen-1(2H)-one was achieved. The sulfanylation reactions of 3,4-dihydronaphthalen-1(2H)-one-O-methyloxime and 2-(methylsulfinyl)-3,4-dihydronaphthalen-1(2H)-one-O-methyloxime by homogenous reaction medium are reported. The products were obtained in good yields and de. The yields, diastereoselectivity and theoretical calculations to all obtained compounds to support the experimental data are compared and discussed.

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).

Background: Tropaeolum majus L. (Tropaeolaceae) is an important medicinal plant belonging to the Tropaeolaceae family, which has 80 species distributed in South and Central America. In Brazil, it is distributed practically throughout the entire territory and it is popularly known as “capuchinha”. In folk medicine its leaves are widely used for treatment of cardiovascular disorders. Despite consistent data showing some acute effects on renal and cardiovascular system, no study has investigated whether Tropaeolum majus extracts is able to exert cardiorenal protective effects after 30 days of treatment, i.e. in a sustained manner. Objective: Investigate the prolonged cardiorenal protective effects of ethanolic extract obtained from Tropaeolum majus (EETM) in rats with renovascular hypertension. Material and Methods: First, EETM was obtained and chemically characterized. Then, we investigated the possible antihypertensive and diuretics effects, including effects on renal haemodynamics, after prolonged treatment (30 days) with EETM (3, 30 and 300 mg/kg). Finally, we examined whether treatment with EETM may affect the angiotensin-converting enzyme (ACE) and oxidative stress, preventing heart and kidney damage in two-kidney, one-clip (2K1C) Goldblatt hypertensive rats. Results: Prolonged treatment with EETM was able to prevent the evolution of renovascular hypertension in 2K1C rats, inducing important renoprotective effects and reducing systemic blood pressure and cardiac hypertrophy. Moreover, it was also identified that these effects may be directly related to significant ACE inhibitory activity and reduction of oxidative stress. Conclusion: This study has brought new scientific evidence of preclinical efficacy of EETM as a cardiorenal protective agent in rats with renovascular hypertension. Key words: Antihypertensive, Cardioprotective, Diuretic, Renoprotective, Tropaeolum majus L.

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.

A new and practical method has been developed for the transformation of racemic α-bromo ketones to chiral α-azido and α-amino ketones with high enantioselectivity using phase transfer, ion-pair mediated reactions with a recoverable chiral quaternary salt (10 mol %) as catalyst in fluorobenzene-water. The process has been generalized to a variety of other attachments including of C, O, S, and NHR.

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.

Objective The objective of this study was to evaluate the frequency of genetic lesions in pharmacists and nurses who prepare and/or handle antineoplastic agents and to evaluate whether there are traces of contaminants in the urine of these professionals. Methods A total of 59 professionals participated in the study, of which 10 were non-exposed professionals (controls), 25 were pharmacists, and 24 were nurses. Key findings There was a significant increase in genetic damage in lymphocytes and cells of the oral mucosa in both pharmacists and nurses. The levels of cyclophosphamide and ifosfamide were also increased in the urine samples from those individuals. Conclusions: These results demonstrate the growing need for genetic biomonitoring and biomonitoring of trace antineoplastic agents in the urine of health professionals who prepare and/or handle antineoplastic agents.

The antioxidant potential of a novel additive, named maleimide p-CH3, and the synergistic effect on biodiesel stabilization when combined with a traditional synthetic antioxidant (e.g., propyl gallate (PG)) as well as alternative additives (e.g., alizarin (ALZ) and citric acid (CA)) were investigated. The additives were combined in binary and/or ternary blends at low concentrations and their effectiveness against soybean biodiesel oxidation in the absence and presence of metal was tested. The effectiveness of binary and ternary blends was also evaluated by the Rancimat® method and compared with total acid number (TAN). The results showed that the combinations presented synergetic effects and were effective in stabilizing biodiesel in accordance with the minimum requirements of EN 14214 and also revealed that the mixture containing PG and p-CH3, even at low concentrations, can be successfully applied for biodiesel preservation. In summary, we report that the biodiesel stability can be obtained by using a reduced amount of additives, suggesting that biodiesel shelf life can be improved in association with a cost reduction when compared to the use of conventional antioxidants.

Compounds featuring weakly-coordinating N-oxides or carbonyl groups, as for instance, quinoline N-oxide and quinonoid systems represent important structural scaffolds with potential biological activities. Due to their biological importance, significant efforts have been devoted to devise robust methods for their step-economical preparation. Among these approaches, the C–H activation strategy has emerged as a powerful, versatile and efficient tool in molecular sciences. This feature article summarizes recent key advances in transition-metal-catalyzed C–H functionalization for A-ring functionalization of heterocyclic and quinoidal compounds by challenging weakly-coordinating entities, published prior to May 2018.

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.

Copper (II) complexes are promising in the development of new synthetic models for cancer treatment. In this context, we synthesized a new copper complex containing the pharmacophore group 1,4-dioxo-2-butenyl, the Bis(((Z)-4-((4-chlorophenyl) amino)-4-oxobut-2-enoyl)oxy) copper compound and we evaluated its antitumor activity in 4 T1 murine mammary adenocarcinoma cells and their toxicogenic effect in Swiss mice. The compound demonstrated cytotoxicity and genotoxicity to 4 T1 cells, and after cell cycle arrest in G1, which occurred by the increase in ATM and p21 expression, it induced the cells to apoptosis by increasing BAX and caspase-7. In vivo the compound was genotoxic in mice but did not show permanent damage, observed by the absence of increased micronucleus frequency, and did not induce changes in the biometric parameters of the animals. These results indicate that the new copper complex, described firstly in this work, presents therapeutic potential for breast cancer.

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.

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.

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.

The complete assignment of the (1)H and (13)C NMR spectra of various 2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides and 2-acetamide-3-methyl-3-nitrososulfanyl-N-aryl-butanamides with p-methoxy, o-chloro and m-chloro substituents is reported.

The analysis of the IR carbonyl band of the 2-substituted N -methoxy- N -methylacetamides Y–CH 2 C(O)N(OMe)Me (Y = F 1 , OMe 2 , OPh 3 , Cl 4 ), supported by B3LYP/6-311++G(3df, 3pd) calculations along with the NBO analysis for 1 – 4 , indicated the existence of cis – gauche conformers i.e. ( c ) and ( g ) for 1 and 3 , ( c 1 , c 2 ) and ( g 1 , g 2 ) for 2 , and ( c ) and ( g 1 , g 2 ) for 4 . In the gas phase, the g conformer population prevails over the c one, for 1 and 3 , the ( c 1 + c 2 ) population prevails over the ( g 1 + g 2 ) one for 2 , and the ( g 1 + g 2 ) conformer population is more abundant than ( c ) one for 4 . In n -hexane solution, the cis conformer is more abundant for 1 – 3 . The occurrence of Fermi resonance in the ν CO region, in n -hexane, precludes the estimative of relative populations of the ( c , g 1 , g 2 ) conformers for 4 . The SCI-PCM calculations agree with the solvent effect on the ν CO band component relative intensities for 1 – 3 . NBO analysis showed that the n N → π co ∗ orbital interaction is the main factor which stabilizes the gauche ( g , g 1 , g 2 ) conformers for 1 – 4 into a larger extent relative to the cis ( c , c 1 , c 2 ) ones. The n Y → π co ∗ , σ C Y → π co ∗ , π co → σ C Y ∗ and π co ∗ → σ C Y ∗ orbital interactions still contribute, but into a minor extent for the stabilization of the gauche conformers relative to the cis ones. The existence of some pyramidalization at the nitrogen atom of the Weinreb amides 1 – 4 is responsible for the occurrence of Y δ − (4)···O δ − (9) and Y δ − (4)···N δ − (7) short contacts in the gauche ( g , g 1 , g 2 ) conformers, which originates strong repulsive Coulombic interactions, acting in opposition to the large orbital stabilization of the gauche conformer with respect to the cis one. Therefore, a delicate balance of the Coulombic and orbital interactions seems to be responsible for the observed stabilization of the gauche ( g , g 1 , g 2 ) and cis ( c , c 1 , c 2 ) conformers, both in the gas phase and in the solution for 1 – 4 . However, the cis conformer predominance, in non polar solvents, for the 2-substituted N -methoxy- N -methyl acetamides 1 – 3 , bearing in α first raw (fluorine and oxygen) atoms, is in the opposite direction to the gauche conformer preference for the corresponding 2-substituted N , N -dialkyl-acetamides.

Background A large number of studies are attempting to identify alternative products from natural sources or synthesized compounds that effectively interact with cancer cells without causing adverse effects on healthy cells. Resorcinolic lipids are a class of bioactive compounds that possess anticancer activity and are able to interact with the lipid bilayer. Therefore, the objective of this study was to synthesize a novel resorcinolic lipid and test its biological proprieties. Methods We aimed to synthesize a novel resorcinolic lipid belonging to the class of cytosporones, AMS049 (3-Heptyl-4,6-dihydroxy-3H-isobenzofuran-1-one) and to evaluate the toxicity of two concentrations of this lipid (7.5 and 10 mg/kg) by determining its genotoxic, mutagenic, immunomodulatory, and apoptotic effects, as well as any biochemical and histopathological alterations in mice treated with cyclophosphamide. The results were analyzed by ANOVA followed by the Tukey test A . level of significance of p

Hybrid materials have seized attention from scientific community mainly as heterogenic catalysts in organic reactions on a large scale succeeding in some organic compounds with high yields. One of the most important classes of hybrid materials used for this purpose involves the complexation of Zn and aminoacids. Herein, we introduced Zn[Pro]2 and Zn[Gly]2 in the synthesis of several β-enaminones via solvent free protocol and using an ultrasound device.

A bicyclo[6.2.1]undecane model compound (VI) of the core structure of the biologically active furanoheliangolide sesquiterpene is synthesized.

th Brazilian Meeting on Organic Synthesis – 15 th BMOS – November 10-13, 2013 Campos do Jordao, Brazil New Synthesis for norbornene from 4-amoniantipyrine Ingridhy Ostaciana Maia Freitas da Silveira (PG), Cristiane Regina Winck (PG), Paola Dias de Oliveira (IC), Roberto da Silva Gomes (PQ), Denis Pires de Lima (PQ), Adilson Beatriz (PQ) 1 Universidade Federal de Mato Grosso do Sul, Institute of Chemistry