This study details the preparation, antileishmanial assay, and in silico analysis of twenty 2-hydroxy-3-(1,2,3-triazolyl)propyl vanillin derivatives. These compounds were synthesized in three steps and evaluated against Leishmania infantum, Leishmania amazonensis, and Leishmania braziliensis promastigotes. Compounds 3s and 3t were the most effective, showing good activity against all Leishmania species tested. Molecular docking indicated that all compounds bind favorably to the sterol 14α-demethylase (CYP51) enzyme from L. infantum. ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis indicated good oral bioavailability, non blood-brain barrier penetration, and high gastrointestinal absorption. Posaconazole and compounds 3e, 3s, and 3t remained stable in the CYP51 binding region during 100 ns molecular dynamics (MD) simulations. Root mean square deviation (RMSD) and root mean square fluctuations (RMSF) analyses from the MD trajectory revealed significant conformational fluctuations of the CYP51 N-terminal, suggesting occasional expulsion of 3e, potentially explaining its higher IC50 (half-maximal inhibitory concentration) values. Pairwise decomposition analyses from molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) calculations highlighted the importance of hydrophobic residues in interacting with the synthesized derivatives. preparation assay 2hydroxy31,2,3triazolylpropyl 2hydroxy3123triazolylpropyl hydroxytriazolylpropyl 2 hydroxy 3 1,2,3 triazolyl propyl 1 derivatives infantum amazonensis promastigotes s t effective tested 14αdemethylase αdemethylase 14α demethylase α CYP (CYP51 L absorption, absorption (absorption distribution metabolism toxicity bioavailability bloodbrain blood brain penetration 3e e CYP5 10 (MD simulations RMSD (RMSD RMSF (RMSF Nterminal, Nterminal N terminal, terminal N-terminal IC IC5 halfmaximal half maximal concentration values PoissonBoltzmann Poisson Boltzmann MM/PBSA MMPBSA MM PBSA (MM/PBSA 2hydroxy31 3triazolylpropyl triazolylpropyl 123 1,2, (CYP5 2hydroxy3 12 1,2 (CYP 2hydroxy 1,

This investigation describes the synthesis of eugenol analogs presenting 1,2,3-triazole fragments and evaluation of their antileishmanial activity. The alkylation of guaiacol (1) with allyl bromide afforded 1-(allyloxy)-2-methoxybenzene (2) (93% yield). The Claisen rearrangement conducted with 1 gave ortho eugenol (3) (82% yield). Alkylation procedures performed with 3 produced 1-allyl-3-methoxy-2-(prop-2-yn-1-yloxy)benzene (4) (73% yield) and 1-allyl-3-methoxy-2-(pent-4-yn-1-yloxy)benzene (6) (53% yield). The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reactions involving alkynes 4 and 6 with different benzylic azides afforded twenty-two eugenol analogs with 1,2,3-triazole functionalities (48-93% yield). We screened the compounds at 10 μmol L 1 against Leishmania braziliensis intracellular amastigotes during macrophage infection. The action of these compounds was compared with the known leishmanicidal drug amphotericin B. None of the analogs were toxic to macrophages at 10 μmol L-1. The cytotoxic concentration at 50% (CC50), effective concentration at 50% (EC50), and selectivity index (SI) were determined to the best compounds 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-chlorobenzyl)-1 H-1,2,3-triazole (8c) and 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-trifluoromethoxybenzyl)-1 H-1,2,3-triazole (8h). They showed a significant leishmanicidal effect, with EC50 of 28.09 µmol L-1 (8c) and 52.03 µmol L-1 (8h). The SIs were 9.7 for 8c and > 5.7 for 8h. These compounds have the potential as new leishmanicidal agents against L. braziliensis and may represent a starting point for the development of alternative treatments for cutaneous leishmaniasis. 1,2,3triazole 123triazole triazole 1,2,3 2 activity (1 1allyloxy2methoxybenzene allyloxymethoxybenzene allyloxy methoxybenzene (2 93% 93 (93 yield. yield . (3 82% 82 (82 1allyl3methoxy2prop2yn1yloxybenzene allylmethoxypropynyloxybenzene methoxy prop yn yloxy benzene (4 73% 73 (73 1allyl3methoxy2pent4yn1yloxybenzene allylmethoxypentynyloxybenzene pent (6 53% 53 (53 copperIcatalyzed copper I catalyzed alkyneazide alkyne azide CuAAC (CuAAC twentytwo twenty two 4893% 4893 48 (48-93 infection B L1. L1 1. 50 CC50, CC50 CC , (CC50) EC50, EC (EC50) SI (SI 42allyl6methoxyphenoxymethyl14chlorobenzyl1 allylmethoxyphenoxymethylchlorobenzyl phenoxymethyl chlorobenzyl 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-chlorobenzyl)- H1,2,3triazole H123triazole Htriazole H c (8c 42allyl6methoxyphenoxymethyl14trifluoromethoxybenzyl1 allylmethoxyphenoxymethyltrifluoromethoxybenzyl trifluoromethoxybenzyl 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-trifluoromethoxybenzyl)- 8h h (8h) effect EC5 2809 28 09 28.0 L- 5203 52 03 52.0 97 9 7 9. 57 5 5. leishmaniasis 3triazole 123 1,2, ( (9 8 (8 yloxybenzene (7 (5 489 (48-9 CC5 (CC50 (EC50 methoxyphenoxymethyl 42allyl6methoxyphenoxymethyl14chlorobenzyl 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-chlorobenzyl) H1 42allyl6methoxyphenoxymethyl14trifluoromethoxybenzyl 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-trifluoromethoxybenzyl) (8h 280 0 28. 520 52. 12 1,2 (48- (CC5 (EC5 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-chlorobenzyl 4-((2-allyl-6-methoxy)phenoxymethyl)-1-(4-trifluoromethoxybenzyl 1, (48 (CC (EC

Abstract The control of weeds in agriculture is mainly conducted with the use of synthetic herbicides. However, environmental and human health concerns and increased resistance of weeds to existing herbicides have increased the pressure on researchers to find new active ingredients for weed control which present low toxicity to non-target organisms, are environmentally safe, and can be applied at low concentrations. It is herein described the synthesis of glycerol-fluorinated triazole derivatives and evaluation of their phytotoxic and cytogenotoxic activities. Starting from glycerol, ten fluorinated triazole derivatives were prepared in four steps. The assessment of them on Lactuca sativa revealed that they present effects on phytotoxic and cytogenotoxic parameters with different degrees of efficiency. The compounds 4a, 4b, 4d, 4e, 4i, and 4j have pre-emergent inhibition behavior, while all the investigated compounds showed post emergent effect. Mechanism of action as clastogenic, aneugenic, and epigenetic were observed in the lettuce root meristematic cells, with alterations as stick chromosome, bridge, delay, c-metaphase, and loss. It is believed that glycerol-fluorinated triazole derivatives possess a scaffold that can be explored towards the development of new chemicals for the control of weed species. However nontarget non target organisms safe concentrations glycerolfluorinated glycerol activities steps efficiency 4a 4b b 4d d 4e e 4i i j preemergent pre behavior effect clastogenic aneugenic cells chromosome bridge delay cmetaphase, cmetaphase c metaphase, metaphase c-metaphase loss species

Eugenol (C10H12O2, 4-allyl-2-methoxyphenol) is a phenolic natural product that has several biological activities and possibilities of applications. It is herein described the synthesis of eugenol-fluorinated triazole derivatives and evaluation of their fungicidal activity. The reaction of eugenol with epichlorohydrin resulted in the preparation of (±)-2-((4-allyl-2-methoxyphenoxy)methyl)oxirane (1) in 88% yield. The azidolysis of 1 with sodium azide gave the azido-alcohol (±)-1-(4-allyl-2-methoxyphenoxy)-3-azidopropan-2-ol (2) in 94% yield. The CuAAc reaction between compound 2 and different terminal alkynes afforded a series of eleven derivatives (3a 3k) within 48-80% yield. All the synthesized compounds were characterized by infrared (IR) and nuclear magnetic resonance (1H and 13C) spectroscopies and high-resolution mass spectrometry. The in vitro inhibitory activity of the compounds on the mycelial growth of a strain of Colletotrichum sp., that causes anthracnose disease on papaya fruits, was evaluated. The best result was observed for compound 1-(4-allyl-2-methoxyphenoxy)-3-(4-(2-fluorophenyl)-1H-1,2,3-triazol-1-yl)propan-2-ol (3d) that showed a mean growth-inhibition zone of 5.10 mm in a well-diffusion assay, and may serve as a template for additional structural modifications, aiming for more potent fungicidal activity.

A novel free PhotoMetrix UVC is proposed for both the operation of a universal serial bus video camera (UVC) and multivariate image analysis, allowing a full solution for point-of-use analysis. A UVC was placed in an open-source 3D-printed chamber illuminated by a white light-emitting diode (LED) with controlled intensity of light. The digital images captured were converted into red, green, and blue (RGB) histograms, and regression models were used within the app. As a proof-of-concept, four adulterants in raw milk samples were determined. The coefficient of determination (R2Cal) for all models was higher than 0.99, and no significant differences (p < 0.05) between the measured and predicted values were identified. The root mean square error of calibration (RMSEC) and root mean square error of cross validation (RMSECV) were satisfactory, with values less than 0.1 and 0.7 g L-1, respectively. The recoveries ranged from 90 to 120% in spiked milk samples, and partial least square (PLS) models showed root mean square error of prediction (RMSEP) of 0.28, 0.33, 0.48 and 0.39 g L-1 for chloride, hypochlorite, hydrogen peroxide and starch, respectively. The PhotoMetrix UVC app was feasible for the colorimetric chemical analysis using a smartphone improving the applicability, mobility, and usability.

Herein, the synthesis of nine novel glycerol-derived 4-alkyl-substituted 1,2,3-triazoles, using the CuI-catalyzed alkyne-azide cycloaddition reaction as the key step, is reported. The triazoles were characterized by infrared and nuclear magnetic resonance (NMR 1H and 13C) spectroscopy and mass spectrometry. The nine prepared compounds were evaluated with regard to their phytotoxic, antiproliferative, and fungicidal activities. The fungicidal activity was assessed on Colletotrichum gloeosporioides, the causative agent of papaya anthracnose. All compounds presented high efficiency (comparable to the commercial fungicide tebuconazole) in inhibiting C. gloeosporioides sporulation. The phytotoxicity of the triazoles was assessed against Lactuca sativa. Germination was the less-affected parameter, whereas the most pronounced effects of the triazoles were on the germination speed index and root growth of the L. sativa seedlings. As indicators of antiproliferative activity, the mitotic index was evaluated along with chromosomal and nuclear alterations, all of which were influenced to different degrees by the triazoles. In addition, all derivatives demonstrated aneugenic and clastogenic actions in meristematic cells of L. sativa roots. Therefore, these 4-alkyl-substituted triazoles may represent a scaffold to be explored for the development of new fungicidal agents.

In the present investigation, a collection of twenty two nerol derivatives, containing 1,2,3-triazolic appendages, was synthesized and screened in vitro for their cytotoxic activity against HL60, Nalm6, and Jurkat human leukemia cells as well as against B16F10 (melanoma cell line). In most cases, derivatives were able to reduce cell viability. The most potent compound (Z)-4-(((3,7-dimethylocta-2,6-dien-1-yl)oxy)methyl)-1-(4-(trifluoromethoxy)benzyl)-1H-1,2,3 triazole showed antiproliferative activity against Jurkat cells and reduced B16F10 cell migration. Physicochemical properties of the compounds were calculated in order to evaluate their potential for drug development. Most of the evaluated physicochemical parameters seemed to be favorable for drug development. In addition, for a better understanding of the biological activity results, 3D quantitative structure-activity relationship (QSAR) studies were carried out. 3D-QSAR studies indicate that the anticancer activities observed for the cell lines HL60 and Jurkat may occur by a similar mechanism of action and the same was found for the Nalm6 and B16F10 cell lines.

A área da Bacia do Marajó apresenta feições geológicas e geomorfológicas devidas principamente à distensão Mesozóica e à neotectônica pós-miocênica. O evento de distensão, com fases do Cretáceo Inferior e Superior, originou quatro sub-bacias que contituem a Bacia do Marajó, com uma espessa seqüência clástica continental mostrando influência marinha. Falhas normais NW e NNW e direcionais NE e ENE controlaram a geometria da bacia. A distensão, relacionada com a abertura do Atlântico Equatorial, propagou-se continente adentro ao longo de zonas de fraqueza crustal dos cinturões orogênicos pré-cambrianos Tumucumaque, Amapá e Araguaia. O evento neotectônico é um regime transcorrente que desenvolveu bacias transtensivas preenchidas por sedimentos marinhos rasos (Formação Pirabas) e seqüências transicionais (Grupo Barreiras) do Terciário Superior, seguidos por depósitos fluviais e seqüências transicionais do Quaternário, derivadas dos rios Amazoans e Tocantins e do estuário do Marajó. A paisagem atual tem morfologia tipicamente estuarina. A morfologia costeira apresenta escarpas em seqüências transicionais do Terciário Superior, enquanto no interior dominam elevações sustentadas por crosta laterítica do Pleistoceno Médio, aparadas por superfície erosiva a 70 m. No leste da Ilha do Marajó são reconhecidas várias gerações de paleocanais com seqüências estuarinas associadas, enquanto no lado oeste predomina uma planície flúvio-marinha.

The Marajó Basin area presents geologic and geomorphologic features chiefly due to the Mesozoic extension and post-Miocene neotectonics. The extension event with an Early and a Late Cretaceous phases originated four sub-basins that constitutes the Marajó Basin, with a thick continental clastic sequence showing marine influence. NW and NNW normal faults and NE and ENE strike-slip faults controlled the basin geometry. The extension, related to the Equatorial Atlantic opening, propagated into the continent along crustal weakness zones of the Precambrian Tumucumaque, Amapá and Araguaia orogenic belts. The neotectonic event is a strike-slip regime which developed transtensional basins filled in by Upper Tertiary shallow marine (Pirabas Formation) and transitional sequences (Barreiras Group), followed by Quaternary fluvial deposits and transitional sequences derived from the Amazon and Tocantins rivers and the Marajoara estuary. The current landscape has a typical estuarine morphology. The coast morphology presents sea-cliffs on transitional Upper Tertiary sequences, while inwards dominate hills sustained by Mid-Pleistocene lateritic crust, with a flat erosive surface at 70 m. In the eastern Marajó Island several generations of paleochannels associated with fluvial-estuarine sequences are recognized, while a fluvial-marine plain is widespread on its western side.

The [3+4] cycloaddition between furan and the oxyallyl cation generated from 1-bromo-1-phenylpropan-2-one (4), resulted in the formation of 2-phenyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (5) in 30% yield. This compound was further converted into 2-phenyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]oct-2-ene (13) in 35.4% yield. The selective effect of compound (13) and its isomer 3-phenyl-6,7-exo-isopropylidenedioxi-8-oxabicyclo[3.2.1]oct -2-ene (1a) on the radicle growth of Sorghum bicolor L. (sorghum) and Cucumis sativus L. (cucumber) were evaluated. For both plants, compound 13 showed to be more potent than its isomer 1a.