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Inspired by the synthetic and biological potential of organotellurium substances, a series of five‐ and six‐membered ring organotelluranes containing a Te−O bond were synthesized and characterized. Theoretical calculations elucidated the mechanism for the oxidation‐cyclization processes involved in the formation of the heterocycles, consistent with chlorine transfer to hydroxy telluride, followed by a cyclization step with simultaneous formation of the new Te−O bond and deprotonation of the OH group. Moreover, theoretical calculations also indicated anti‐diastereoisomers to be major products for two chirality center–containing compounds. Antileishmanial assays against Leishmania amazonensis promastigotes disclosed 1,2λ4‐oxatellurane LQ50 (IC50=4.1±1.0; SI=12), 1,2λ4‐oxatellurolane LQ04 (IC50=7.0±1.3; SI=7) and 1,2λ4‐benzoxatellurole LQ56 (IC50=5.7±0.3; SI=6) as more powerful and more selective compounds than the reference, being up to four times more active. A stability study supported by 125Te NMR analyses showed that these heterocycles do not suffer structural modifications in aqueous‐organic media or at temperatures up to 65 °C. [ABSTRACT FROM AUTHOR]

The harmful impact caused by pesticides on human health and the environment necessitates the development of efficient degradation processes and control of prohibited stocks of such substances. Organophosphates (OPs) are among the most used agrochemicals in the world and their degradation can proceed through several possible pathways. Investigating the reactivity of OPs with nucleophilic species allows one to propose new and efficient catalyst scaffolds for use in detoxification. In light of the remarkable catalytic activity of imidazole (IMZ) at promoting dephosphorylation processes of OPs, the reactivity of 4(5)‐hydroxymethylimidazole (HMZ) with diethyl‐2,4‐dinitrophenylphosphate (DEDNPP) and Paraoxon are evaluated by combining experimental and theoretical approaches. It is observed that HMZ is an efficient and regiospecific catalyst with reactivity modulated by competing tautomers. To propose an optimal IMZ‐based catalyst, quantum chemical calculations were performed for monosubstituted 4(5)IMZ derivatives that might cleave DEDNPP. Both inductive effects and hydrogen bonding by the substituents are shown to influence barriers and mechanisms. [ABSTRACT FROM AUTHOR]

Natural products represent a valuable source for discovery of antiparasitic agents. Here, we describe the antiparasitic activity from essential oils extracted from leaves ofGuatteria friesiana(EOGF) andGuatteria pogonopus(EOGP) (Annonaceae). The essential oils were obtained by hydrodistillation and analyzed by GC/MS and GC-FID. The sesquiterpenes are more abundant in both essential oils.G. friesianaare dominated by β-eudesmol (51.9%), γ-eudesmol (18.9%) andα-eudesmol (12.6%). The major compounds identified for EOGP were spathulenol (24.8%), γ-amorphene (14.7%) and germacrene D (11.8%). The essential oils demonstrated potent trypanocidal and antimalarial activities with values of IC50lower than 41.3 μg/mL.EOGF also inhibits the proliferation of amastigotes. In addition, we identified significant ultrastructural alterations induced by the essential oils, especially in the cell membrane, Golgi complex, endoplasmatic reticulum and mitochondria. The results presented herein reinforce the potential of other members of this family for search of antiparasitic compounds. [ABSTRACT FROM AUTHOR]

Imidazole (IMZ) rings catalyze many biological dephosphorylation processes. The methyl positioning effect on IMZs reactivity has long intrigued scientists and its full understanding comprises a promising tool for designing highly efficient IMZ-based catalysts. We evaluated all monosubstituted methylimidazoles (xMEI) in the reaction with diethyl 2,4-dinitrophenyl phosphate by kinetics studies, NMR analysis and DFT calculations. All xMEI showed remarkable rate enhancements, up to 1.9×105 fold, compared with spontaneous hydrolysis. Unexpectedly, the electron-donating methyl group acts to decrease the reactivity of the xMEI compared to IMZ, except for 4(5)methylimidazole, (4(5)MEI). This behavior was attributed to both electronic and steric effects. Moreover, reaction intermediates were monitored by NMR and surprisingly, the reactivity of the two different 4(5)MEI tautomers was distinguished. [ABSTRACT FROM AUTHOR]

Xylopia laevigata (Annonaceae), known locally as “meiú” or “pindaíba”, is widely used in folk medicine in Northeastern Brazil. In the present work, we performed phytochemical analyses of the stem of X. laevigata, which led to the isolation of 19 alkaloids: (–)-roemerine, (+)-anonaine, lanuginosine, (+)-glaucine, (+)-xylopine, oxoglaucine, (+)-norglaucine, asimilobine, (–)-xylopinine, (+)-norpurpureine, (+)-N-methyllaurotetanine, (+)-norpredicentrine, (+)-discretine, (+)-calycinine, (+)-laurotetanine, (+)-reticuline, (–)-corytenchine, (+)-discretamine and (+)-flavinantine. The in vitro cytotoxic activity toward the tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia) and HL-60 (human promyelocytic leukemia) and non-tumor peripheral blood mononuclear cells (PBMCs) was tested using the Alamar Blue assay. Lanuginosine, (+)-xylopine and (+)-norglaucine had the highest cytotoxic activity. Additionally, the pro-apoptotic effects of lanuginosine and (+)-xylopine were investigated in HepG2 cells using light and fluorescence microscopies and flow cytometry-based assays. Cell morphology consistent with apoptosis and a marked phosphatidylserine externalization were observed in lanuginosine- and (+)-xylopine-treated cells, suggesting induction of apoptotic cell death. In addition, (+)-xylopine treatment caused G2/M cell cycle arrest in HepG2 cells. These data suggest that X. laevigata is a potential source for cytotoxic alkaloids. [ABSTRACT FROM AUTHOR]

Hypervalency, leishmania, oxidation-cyclization mechanism, 125Te NMR spectroscopy, tellurium Keywords: hypervalency; leishmania; oxidation-cyclization mechanism; 125Te NMR spectroscopy; tellurium EN hypervalency leishmania oxidation-cyclization mechanism 125Te NMR spectroscopy tellurium 14356 14356 1 10/21/21 20211019 NES 211019 B Explaining the oxidation-cyclization mechanism b of heterocycles containing Te-O bonds. Cover Feature: Synthesis, Mechanism Elucidation and Biological Insights of Tellurium(IV)-Containing Heterocycles (Chem. Eur. J. 58/2021). [Extracted from the article]

Green tea is a product obtained from the processing of fresh leaves of Camellia sinensis (L.) O. Kuntze species. In this study, the influence of climatic parameters on the chemical composition of green tea cultivars ('Yabukita' and 'Yutakamidori') over the harvest was evaluated using HR-MAS NMR. 'Yabukita' showed higher concentrations of epicatechin while higher amounts of theanine and caffeine were found in 'Yutakamidori'. The decline of theanine was associated with high average maximum temperature and solar radiation index, this latter also seemed to be responsible for relevant changes in epicatechin concentrations. It was not possible to associate any trend between climatic parameters and caffeine concentration. Fluctuations in linolenic acid concentration were monitored during the harvest period and were associated with the plant's defense mechanism. Monitoring of green tea over seasons and correlating the fluctuations of compounds to climatic parameters might become an efficient strategy for establishing quality standards for green teas., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Organophosphate (OP) pesticides are responsible for numerous human deaths every year. Nucleophilic substitution is an important method to mitigate the toxicity of obsolete stocks of OPs. Herein, the degradation of O , O -diethyl-2,4-dinitrophenyl phosphate (DEDNPP) and pesticide diethyl-4-nitrophenyl phosphate (Paraoxon) promoted by 1,2,4-triazole (TAZ) was investigated by means of kinetic studies, nuclear magnetic resonance (NMR) analyses, and theoretical calculations. Results showed fast degradation of OPs is promoted by the anionic form of the nucleophile (TAZ(-)) in pH > 8.5 (optimal at pH = 11). Rate enhancements of 10 6 and 10 5 -fold in relation to neutral hydrolysis of DEDNPP and Paraoxon were observed, respectively, consistent with alpha-nucleophiles reactivity. TAZ(-) regioselectively promotes the degradation of DEDNPP via P-O bond break, forming a quickly hydrolyzable phosphorylated intermediate, regenerating the nucleophile. Calculations using M06-2X/6-311++G(d,p) level of theory revealed that the equivalent nitrogen atoms of TAZ(-) are the main nucleophilic center of the molecule. This study expands the knowledge on the reactivity of iminic compounds as detoxificant agents of OPs, indicating the efficiency and selectivity of TAZ(-) in aqueous medium, encouraging the design of novel TAZ-based catalysts.

The harmful impact caused by pesticides on human health and the environment necessitates the development of efficient degradation processes and control of prohibited stocks of such substances. Organophosphates (OPs) are among the most used agrochemicals in the world and their degradation can proceed through several possible pathways. Investigating the reactivity of OPs with nucleophilic species allows one to propose new and efficient catalyst scaffolds for use in detoxification. In light of the remarkable catalytic activity of imidazole (IMZ) at promoting dephosphorylation processes of OPs, the reactivity of 4(5)-hydroxymethylimidazole (HMZ) with diethyl-2,4-dinitrophenylphosphate (DEDNPP) and Paraoxon are evaluated by combining experimental and theoretical approaches. It is observed that HMZ is an efficient and regiospecific catalyst with reactivity modulated by competing tautomers. To propose an optimal IMZ-based catalyst, quantum chemical calculations were performed for monosubstituted 4(5)IMZ derivatives that might cleave DEDNPP. Both inductive effects and hydrogen bonding by the substituents are shown to influence barriers and mechanisms., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Xylopia laevigata, popularly known as "meiú" and "pindaíba", is a medicinal plant used in the folk medicine of the Brazilian Northeast for several purposes. The chemical constituents of the essential oil from leaves of X. laevigata, collected from wild plants growing at three different sites of the remaining Atlantic forest in Sergipe State (Brazilian Northeast), were analyzed by GC/FID and GC/MS. The effect of the essential oil samples was assessed on tumor cells in culture, as well on tumor growth in vivo. All samples of the essential oil were dominated by sesquiterpene constituents. A total of 44 compounds were identified and quantified. Although some small differences were observed in the chemical composition, the presence of γ-muurolene (0.60-17.99%), δ-cadinene (1.15-13.45%), germacrene B (3.22-7.31%), α-copaene (3.33-5.98%), germacrene D (9.09-60.44%), bicyclogermacrene (7.00-14.63%), and (E)-caryophyllene (5.43-7.98%) were verified as major constituents in all samples of the essential oil. In the in vitro cytotoxic study, the essential oil displayed cytotoxicity to all tumor cell lines tested, with the different samples displaying a similar profile; however, they were not hemolytic or genotoxic. In the in vivo antitumor study, tumor growth inhibition rates were 37.3-42.5%. The treatment with the essential oil did not significantly affect body weight, macroscopy of the organs, or blood leukocyte counts. In conclusion, the essential oil from the leaves of X. laevigata is chemically characterized by the presence of γ-muurolene, δ-cadinene, germacrene B, α-copaene, germacrene D, bicyclogermacrene, and (E)-caryophyllene as major constituents and possesses significant in vitro and in vivo anticancer potential., (Georg Thieme Verlag KG Stuttgart · New York.)