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1.
Biomed Chromatogr ; 38(7): e5891, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38773686

RESUMO

The aim of this study was to analyze the phytochemical profile of Acacia cyclops trunk bark ethyl acetate extract using LC-tandem mass spectrometry for the first time, along with evaluating its antioxidant and anti-tyrosinase properties. Consequently, we determined the total phenolic and flavonoid contents of the extract under investigation and identified and quantified 19 compounds, including phenolic acids and flavonoids. In addition to assessing their antioxidant potential against DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2'-azino-bis-[3-ethylbenzothiazoline-6-sulfonic] acid) assays, in vitro and in silico studies were conducted to evaluate the tyrosinase inhibitory properties of the A. cyclops extract. The ethyl acetate trunk bark extract exhibited a substantial total phenolic content and demonstrated significant antioxidant activity in terms of free radical scavenging, as well as notable tyrosinase inhibitory action (half-maximal inhibitory concentration [IC50] = 14.08 ± 1.10 µg/mL). The substantial anti-tyrosinase activity of the examined extract was revealed through molecular docking analysis and druglikeness prediction of the main selected compounds. The findings suggest that A. cyclops extract holds promise as a potential treatment for skin hyperpigmentation disorders.


Assuntos
Acacia , Antioxidantes , Inibidores Enzimáticos , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase , Casca de Planta , Extratos Vegetais , Monofenol Mono-Oxigenase/antagonistas & inibidores , Acacia/química , Casca de Planta/química , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/análise , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/análise , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/análise , Espectrometria de Massas em Tandem/métodos , Flavonoides/química , Flavonoides/análise , Flavonoides/farmacologia , Fenóis/química , Fenóis/análise , Fenóis/farmacologia , Cromatografia Líquida/métodos
2.
Drug Chem Toxicol ; : 1-15, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38508716

RESUMO

This study aimed to investigate the effects of combined exposure to noise (85 dB(A)) and inhaled Toluene (300 ± 10 ppm) on rat lung health. It also aimed to assess the potential therapeutic effects of Olea europaea L. leaves extract (OLE) (40 mg/kg/day) using biochemical, histopathological, and immunohistochemical (IHC) analyses, as well as determination of pro-inflammatory cytokines (TNF-α and IL-1ß), and in silico Docking studies. The experiment involved forty-two male Wistar rats divided into seven groups, each exposed to a 6-week/6-hour/day regimen of noise and Toluene. The groups included a control group, rats co-exposed to noise and Toluene, and rats co-exposed to noise and Toluene treated with OLE for different durations. The results indicated that noise and Toluene exposure led to structural damage in lung tissue, oxidative harm, and increased levels of pro-inflammatory cytokines (TNF-α and IL-1ß). However, the administration of OLE extract demonstrated positive effects in mitigating these adverse outcomes. OLE treatment reduced lipid peroxidation and enhanced the activities of catalase and superoxide dismutase, indicating its anti-oxidant properties. Furthermore, OLE significantly decreased the levels of pro-inflammatory cytokines compared to the groups exposed to noise and Toluene without OLE treatment. Moreover, the in silico investigation substantiated a robust affinity between COX-2 and OLE components, affirming the anti-inflammatory activity. Overall, our findings suggest that OLE possesses anti-inflammatory and anti-oxidative properties that mitigate the adverse effects of concurrent exposure to noise and Toluene.

3.
Chem Biodivers ; 21(1): e202300876, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38037520

RESUMO

The purpose of the present work was to develop a phytocosmetic sunscreen emulsion with antioxidant activity and an anti-melanogenic effect, containing an anthraquinone-enriched extract of Rhamnus alaternus (A.E.). Our findings demonstrated that A.E. decreased the levels of reactive oxygen species, DNA damage, and malondialdehyde induced by UVA in human keratinocytes and melanocytes. Furthermore, the calculated SPF value in vitro of the cream containing A.E. was 14.26±0.152. Later, it was shown that A.E. extract had an inhibitory effect on the amount of melanin. This extract could also reduce B16F10 intracellular tyrosinase activity. Besides, docking studies were carried out to provide a logical justification for the anti-tyrosinase potential. The findings showed that, A.E. may provide protection against UVA-induced oxidative stress and could be thought of as a viable treatment for hyperpigmentation disorders.


Assuntos
Rhamnus , Humanos , Antioxidantes/farmacologia , Estresse Oxidativo , Espécies Reativas de Oxigênio , Melaninas , Antraquinonas/farmacologia
4.
Org Biomol Chem ; 21(47): 9379-9391, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37975744

RESUMO

Two quinidine-functionalized coumarin molecular probes have been synthesized and have been found to bind metal cations (Cd2+, Co2+, Cu2+, Fe2+, Hg2+, Ni2+, and Zn2+) with high affinity in organic-aqueous media (DMSO-HEPES). The chemodosimeters coordinate with the Zn2+ ions in a two-to-one ratio (molecular probe : Zn2+) with a log ß of 10.0 M-2. Upon the addition of the closed-shell metal ions studied, a fluorescence turn-on via an excimer formation is seen at 542 nm due to the quinaldine moiety adopting a syn arrangement when coordinated to the metal Zn2+ ions. Confocal microscopy monitored free Zn2+ ions in the Human Embryonic Kidney cell line HEK293 by coordinating with the chemodosimter.


Assuntos
Mercúrio , Metais , Humanos , Células HEK293 , Íons , Cátions , Células HeLa , Corantes Fluorescentes
5.
Chem Biodivers ; 20(3): e202200978, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36808818

RESUMO

In this work, essential oils extracted from roots and aerial parts of Inula graveolens by hydrodistillation and their fractions obtained by chromatographic simplification were first investigated for their chemical composition by GC/MS and then evaluated for the first time for their repellency and contact toxicity properties against Tribolium castaneumadults. Twenty-eight compounds were identified in roots essential oil (REO), which accounted for 97.9 % of the total oil composition, with modhephen-8-ß-ol (24.7 %), cis-arteannuic alcohol (14.8 %), neryl isovalerate (10.6 %) and thymol isobutyrate (8.5 %) as major constituents. Twenty-two compounds were found in the essential oil from aerial parts (APEO), which accounted for 93.9 % of the total oil, with borneol (28.8 %), caryophylla-4(14),8(15)-dien-6-ol (11.5 %), caryophyllene oxide (10.9 %), τ-cadinol (10.5 %) and bornyl acetate (9.4 %) as main compounds.REO and APEO displayed stronger repellency after 2 h of exposure (80.0 and 90.0 %, respectively) against T. castaneum at the concentration of 0.12 µL/cm2 . After fractionation, fractions R4 and R5 exhibited greater effects (83.3 % and 93.3 %, respectively) than the roots essential oil. Furthermore, the fractions AP2 and AP3 showed higher repellency (93.3 and 96.6 %, respectively) than the aerial parts oil. The LD50 values of oils from roots and aerial parts topically applied were 7.44 % and 4.88 %, respectively. Results from contact toxicity assay showed that fraction R4 was more effective than the roots oil with LD50 value of 6.65 %. These results suggests that essential oils of roots and aerial parts from I. graveolens may be explored as potential natural repellent and contact insecticides against T. castaneum in stored products.


Assuntos
Besouros , Repelentes de Insetos , Inseticidas , Inula , Óleos Voláteis , Tribolium , Animais , Repelentes de Insetos/farmacologia , Repelentes de Insetos/química , Inseticidas/química , Óleos Voláteis/química , Componentes Aéreos da Planta/química
6.
Chem Biodivers ; 20(1): e202200533, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36325999

RESUMO

Since ancient times the oil from date palm pits (Phoenix dactylifera L.) has been used to heal wounds. In order to prove this traditional usage of the pits, this oil was extracted from the pits of the Tunisian cultivar 'Alig' and its physico-chemical properties and the chemical composition were evaluated. The fatty acid profile, evidenced by GC, allowed to classify this oil as an oleic-myristic acid oil with a clear abundance of oleic acid (53.66 %). 1 H and 13 C-NMR as well as FT-IR analyses confirmed the presence of fatty acids in triglyceride forms. Furthermore, in vivo wound healing activity of a cream formulated from the extracted oil was performed, for the first time, using a rat model and was compared to placebo cream and a commercial formulation, MEBO®. This study showed that the test cream promoted the healing of pressure ulcers better than the placebo cream and the MEBO® ointment. The results showed that this vegetable oil is able to improve the healing of infected wounds in rats, thus supporting its traditional use. The contribution of the main oleic, linoleic and myristic acids that can be derived from enzymatic hydrolysis to the healing activity of the whole pits oil was predicted by in silico study and the calculated pharmacokinetics parameters.


Assuntos
Phoeniceae , Ratos , Animais , Phoeniceae/química , Simulação de Acoplamento Molecular , Espectroscopia de Infravermelho com Transformada de Fourier , Óleos de Plantas/química , Cicatrização , Ácidos Graxos/análise , Ácido Oleico
7.
Molecules ; 28(12)2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37375209

RESUMO

As part of the valorization of agricultural waste into bioactive compounds, a series of structurally novel oleanolic acid ((3ß-hydroxyolean-12-en-28-oic acid, OA-1)-phtalimidines (isoindolinones) conjugates 18a-u bearing 1,2,3-triazole moieties were designed and synthesized by treating an azide 4 previously prepared from OA-1 isolated from olive pomace (Olea europaea L.) with a wide range of propargylated phtalimidines using the Cu(I)-catalyzed click chemistry approach. OA-1 and its newly prepared analogues, 18a-u, were screened in vitro for their antibacterial activity against two Gram-positive bacteria, Staphylococcus aureus and Listeria monocytogenes, and two Gram-negative bacteria, Salmonella thyphimurium and Pseudomonas aeruginosa. Attractive results were obtained, notably against L. monocytogenes. Compounds 18d, 18g, and 18h exhibited the highest antibacterial activity when compared with OA-1 and other compounds in the series against tested pathogenic bacterial strains. A molecular docking study was performed to explore the binding mode of the most active derivatives into the active site of the ABC substrate-binding protein Lmo0181 from L. monocytogenes. Results showed the importance of both hydrogen bonding and hydrophobic interactions with the target protein and are in favor of the experimental data.


Assuntos
Antibacterianos , Ácido Oleanólico , Antibacterianos/química , Ácido Oleanólico/farmacologia , Triazóis/farmacologia , Triazóis/química , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Estrutura Molecular
8.
Molecules ; 27(16)2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-36014333

RESUMO

In the present study, we assess tyrosol derivatives bearing 3,5-disubstituted isoxazoles and 1,4-disubstituted triazoles for their ability to inhibit the proliferation of K562 cells derived from leukemia as well as primary chronic myeloid leukemia (CML) cells obtained from the peripheral blood of 15 CML patients including 10 patients with untreated chronic phase and 5 patients with resistance against imatinib or multiple TKI. Our results showed that most derivatives displayed significant anti-proliferative activity against K562 cells in a dose-dependent manner. Among them, compounds 3d and 4a exhibited greater potent anticancer activity with respective IC50 values of 16 and 18 µg/mL (45 µM and 61 µM). Interestingly, compound 3d inhibited CML cell proliferation not only in newly diagnosed but also in imatinib-resistant patients. We demonstrated that the anti-proliferative effect of this compound is mediated by a pro-apoptotic activity by promoting oxidative stress and modulating the activity of the Akt, p38 MAPK and Erk 1/2 pathways. In conclusion, our data highlight the potential of this class of derivative as a novel promising therapeutic agent for CML therapy.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Humanos , Mesilato de Imatinib/farmacologia , Isoxazóis/farmacologia , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Álcool Feniletílico/análogos & derivados , Triazóis/farmacologia , Triazóis/uso terapêutico
9.
Molecules ; 27(16)2022 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-36014537

RESUMO

In addition to vaccines, antiviral drugs are essential in order to suppress COVID-19. Although some inhibitor candidates have been determined to target the SARS-CoV-2 protein, there is still an urgent need to continue researching novel inhibitors of the SARS-CoV-2 main protease 'Omicron P132H', a protein that has recently been discovered. In the present study, in the search for therapeutic alternatives to treat COVID-19 and its recent variants, we conducted a structure-based virtual screening using docking studies for a new series of pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives 5-13, which were synthesized from the condensation reaction of pyrazolopyrimidinone-hydrazide (4) with a series of electrophiles. Some significant ADMET predictions-in addition to the docking results-were obtained based on the types of interactions formed and the binding energy values were compared to the reference anti- SARS-CoV-2 redocked drug nirmatrelvir.


Assuntos
Tratamento Farmacológico da COVID-19 , Compostos Heterocíclicos , Antivirais/química , Antivirais/farmacologia , Compostos Heterocíclicos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/química , SARS-CoV-2
10.
Bioorg Chem ; 114: 105071, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34130108

RESUMO

Two series of 3,5-disubstituted isoxazoles (6a-e) and 1,4-disubstituted triazoles (8a-e) derivatives have been synthesized from tyrosol (1), a natural phenolic compound, detected in several natural sources such as olive oil, and well-known by its wide spectrum of biological activities. Copper-catalyzed microwave-assisted 1,3-dipolar cycloaddition reactions between tyrosol-alkyne derivative 2 and two series of aryl nitrile oxides (5a-e) and azides (7a-e) regiospecifically afforded 3,5-disubstituted isoxazoles (6a-e) and 1,4-triazole derivatives (8a-e), respectively in quantitative yields. Synthesized compounds were purified and characterized by spectroscopic means including 1D and 2D NMR techniques and HRMS analysis. The newly prepared hybrid molecules have been evaluated for their anticancer and hemolytic activities. Results showed that most derivatives displayed significant antiproliferative activity against human glioblastoma cancer cells (U87) in a dose-dependent manner. Compounds 6d (IC50 = 15.2 ± 1.0 µg/mL) and 8e (IC50 = 21.0 ± 0.9 µg/mL) exhibited more potent anticancer activity. Moreover, most derivatives displayed low hemolytic activity, even at higher concentrations which suggested that these classes of compounds are suitable candidates for further in vivo investigations. The obtained results allow us to consider the newly synthesized isoxazole- and triazole-linked tyrosol derivatives as promising scaffolds for the development of effective anticancer agents.


Assuntos
Antineoplásicos/farmacologia , Glioblastoma/tratamento farmacológico , Isoxazóis/farmacologia , Álcool Feniletílico/análogos & derivados , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glioblastoma/patologia , Humanos , Isoxazóis/química , Estrutura Molecular , Álcool Feniletílico/química , Álcool Feniletílico/farmacologia , Relação Estrutura-Atividade , Triazóis/química , Células Tumorais Cultivadas
11.
Int J Mol Sci ; 22(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34638600

RESUMO

To explore a new set of anticancer agents, a novel series of pyrazolo[4,3-e]pyrido[1,2-a]pyrimidine derivativeshave been designed and synthesized viacyclocondensation reactions of pyrazolo-enaminone with a series of arylidenemalononitriles; compound 5 was obtained from 5-amino-4-cyanopyrazole. The structures of the target compounds were investigated by spectral techniques and elemental analysis (IR, UV-Vis, 1H NMR, 13C NMR and ESI-MS). All compounds were evaluated for their in vitro cytotoxicity employing a panel of different human tumor cell lines, A375, HT29, MCF7, A2780, FaDu as well as non-malignant NIH 3T3 and HEK293 cells. It has been found that the pyrazolo-pyrido-pyrimidine analog bearing a 4-Br-phenyl moiety was the most active toward many cell lines with EC50 values ranging between 9.1 and 13.5 µM. Moreover, in silico docking studies of the latter with six anticancer drug targets, i.e., DHFR, VEGFR2, HER-2/neu, hCA-IX, CDK6 and LOX5, were also performed, in order to gain some insights into their putative mode of binding interaction and to estimate the free binding energy of this bioactive molecule.


Assuntos
Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Pirimidinas/farmacologia , Animais , Linhagem Celular , Linhagem Celular Tumoral , Simulação por Computador , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células HEK293 , Células HT29 , Humanos , Células MCF-7 , Camundongos , Simulação de Acoplamento Molecular/métodos , Células NIH 3T3 , Pirazóis/farmacologia
12.
Molecules ; 26(20)2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34684683

RESUMO

A series of novel naphthopyrano[2,3-d]pyrimidin-11(12H)-one containing isoxazole nucleus 4 was synthesized under microwave irradiation and classical conditions in moderate to excellent yields upon 1,3-dipolar cycloaddition reaction using various arylnitrile oxides under copper(I) catalyst. A one-pot, three-component reaction, N-propargylation and Dimroth rearrangement were used as the key steps for the preparation of the dipolarophiles3. The structures of the synthesized compounds were established by 1H NMR, 13C NMR and HRMS-ES means. The present study aims to also predict the theoretical assembly of the COVID-19 protease (SARS-CoV-2 Mpro) and to discover in advance whether this protein can be targeted by the compounds 4a-1 and thus be synthesized. The docking scores of these compounds were compared to those of the co-crystallized native ligand inhibitor (N3) which was used as a reference standard. The results showed that all the synthesized compounds (4a-l) gave interesting binding scores compared to those of N3 inhibitor. It was found that compounds 4a, 4e and 4i achieved greatly similar binding scores and modes of interaction than N3, indicating promising affinity towards SARS-CoV-2 Mpro. On the other hand, the derivatives 4k, 4h and 4j showed binding energy scores (-8.9, -8.5 and -8.4 kcal/mol, respectively) higher than the Mpro N3 inhibitor (-7.0 kcal/mol), revealing, in their turn, a strong interaction with the target protease, although their interactions were not entirely comparable to that of the reference N3.


Assuntos
Antivirais/síntese química , Desenho de Fármacos , Isoxazóis/química , Pirimidinonas/química , Antivirais/metabolismo , Antivirais/uso terapêutico , Sítios de Ligação , COVID-19/virologia , Química Click , Proteases 3C de Coronavírus/química , Proteases 3C de Coronavírus/metabolismo , Humanos , Micro-Ondas , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , Inibidores de Proteases/uso terapêutico , SARS-CoV-2/isolamento & purificação , Relação Estrutura-Atividade , Termodinâmica , Tratamento Farmacológico da COVID-19
13.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500647

RESUMO

Diabetes mellitus is a major health problem globally. The management of carbohydrate digestion provides an alternative treatment. Flavonoids constitute the largest group of polyphenolic compounds, produced by plants widely consumed as food and/or used for therapeutic purposes. As such, isoxazoles have attracted the attention of medicinal chemists by dint of their considerable bioactivity. Thus, the main goal of this work was to discover new hybrid molecules with properties of both flavonoids and isoxazoles in order to control carbohydrate digestion. Moreover, the trifluoromethyl group is a key entity in drug development, due to its strong lipophilicity and metabolic stability. Therefore, the present work describes the condensation of a previously synthesized trifluoromethylated flavonol with different aryl nitrile oxides, affording 13 hybrid molecules indicated as trifluoromethylated flavonoid-based isoxazoles. The structures of the obtained compounds were deduced from by 1H NMR, 13C NMR, and HRMS analysis. The 15 newly synthesized compounds inhibited the activity of α-amylase with an efficacy ranging from 64.5 ± 0.7% to 94.7 ± 1.2% at a concentration of 50 µM, and with IC50 values of 12.6 ± 0.2 µM-27.6 ± 1.1 µM. The most effective compounds in terms of efficacy and potency were 3b, 3h, 3j, and 3m. Among the new trifluoromethylated flavonoid-based isoxazoles, the compound 3b was the most effective inhibitor of α-amylase activity (PI = 94.7 ± 1.2% at 50 µM), with a potency (IC50 = 12.6 ± 0.2 µM) similar to that of the positive control acarbose (IC50 = 12.4 ± 0.1 µM). The study of the structure-activity relationship based on the molecular docking analysis showed a low binding energy, a correct mode of interaction in the active pocket of the target enzyme, and an ability to interact with the key residues of glycosidic cleavage (GLU-230 and ASP-206), explaining the inhibitory effects of α-amylase established by several derivatives.


Assuntos
Fármacos Antiobesidade/farmacologia , Diabetes Mellitus/tratamento farmacológico , Flavonoides/farmacologia , Hipoglicemiantes/farmacologia , Isoxazóis/farmacologia , alfa-Amilases/antagonistas & inibidores , Fármacos Antiobesidade/química , Diabetes Mellitus/metabolismo , Flavonoides/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Hipoglicemiantes/química , Isoxazóis/química , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , alfa-Glucosidases/metabolismo
14.
Molecules ; 26(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669825

RESUMO

The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4-70.2%) were detected, mainly consisting of caryophyllene oxide (13.1-26.6%), carotol (9.2-21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2-15.5%) and humulene epoxide II (2.6-7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from 25.7 to 96.5 µg/mL. In addition, the essential oil and its fraction E.2 revealed a cytotoxic activity against colorectal carcinoma cell line, with IC50 values lower than 30 µg/mL. This is the first report on the chemical composition and cytotoxic activity of the trunk bark essential oil of T. articulata.


Assuntos
Cupressaceae/química , Cupressaceae/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Casca de Planta/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fracionamento Químico , Humanos , Concentração Inibidora 50 , Tunísia
15.
Bioorg Chem ; 102: 104093, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32717693

RESUMO

Previously phytochemical investigations carried out on the flowers and trunk bark extracts of Citharexylum spinosum L. tree, allowed the isolation of twenty molecules belonging to several families of natural substances [triterpene acids, iridoid glycosides, phenylethanoid glycosides, 8,3'-neolignan glycosides, together with other phenolic compounds]. In the present work, a biological evaluation (anti-tyrosinase, anticholinesterase and cytotoxic activities) was performed on the prepared extracts and the isolated secondary metabolites. The results showed that the EtOAc extract of the trunk bark displayed the highest anti-tyrosinase effect with a percent inhibition of 55.0 ± 1.8% at a concentration of 100 µg/mL. The highest anticholinesterase activity was presented by the same extract with an IC50 value of 99.97 ± 3.01 µg/mL. The EtOAc extract of flowers and that of the trunk bark displayed the best cytotoxic property with IC50 values of 96.00 ± 2.85 and 88.75 ± 2.00 µg/mL, respectively, against the human cervical cancer cell line (HeLa), and IC50 values of 188.23 ± 3.88 and 197.00 ± 4.25 µg/mL, respectively, against the human lung cancer (A549) cell lines. Biological investigation of the pure compounds showed that the two 8,3'-neolignan glycosides, plucheosides D1-D2, generate the highest anti-tyrosinase potency with a percent inhibition of 61.4 ± 2.0 and 79.5 ± 2.3%, respectively, at a concentration of 100 µM. The iridoid glycosides exhibited a significant anticholinesterase activity with IC50 values ranging from 17.19 ± 1.02 to 52.24 ± 2.50 µM. Triterpene pentacyclic acids and iridoid glycosides exerted encouraging cytotoxic effects against HeLa with IC50 values ranging from 9.00 ± 1.10 to 25.00 ± 1.00 µM. The study of the structure-activity relationship (SAR) has been sufficiently and widely discussed. The natural compounds that exhibited the significant bioactivities were docked.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Verbenaceae/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colinesterases/metabolismo , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Humanos , Camundongos , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
16.
Chem Biodivers ; 17(1): e1900419, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31721431

RESUMO

This work investigated the polar (PC: protein, amino acid and metabolite) and non-polar (NPC: fatty acid) compounds and bioactivity characteristics of the EBN harvested from the state of Johor in Malaysia. The electrophoretic gels exhibited 15 protein bands (16-173 kD) with unique protein profile. Amino acids analysis by AccQ⋅Tag method revealed 18 types of amino acids in EBN. Metabolite profiling was performed using High-Performance Liquid Chromatography coupled with Quadrupole Time-of-Flight Mass Spectrometer (HPLC-QTOF/MS) technique and a total of 54 compounds belonging to different groups were detected and identified. These findings help to uncover the relation of therapeutic activity of EBN. The EBN was further extracted with AcOEt and BuOH. The AcOEt extract was fractionated into three fractions (F1 -F3 ), and the high triglyceride content in F2 was verified by gC-FID. The three groups of fatty acids discovered in EBN are 48.43 % of poly-unsaturated (PUFA), 25.35 % of saturated fatty acids (SFA) and 24.74 % of mono-unsaturated fat (MUFA). This is the first time to report results ofEBN, BuOH, and AcOEt extracts and of fraction F2 (TEBN) on their analysis for their antioxidant activities by DPPH, ABTS and catalase assay and for their paraoxonase and anti-tyrosinase activities. The results showed that TEBN exhibited the significant bioactivity in all assays. These findings suggest that TEBN is a good source for natural bioactive compounds in promoting body vigor. Current work widened the content of EBN especially on the triglyceride and also marked the content of specific location (Johor, Malaysia) of EBN origin.


Assuntos
Aminoácidos/análise , Produtos Biológicos/análise , Produtos Biológicos/química , Aves , Ácidos Graxos/análise , Análise de Alimentos , Comportamento de Nidação , Proteínas/análise , Aminoácidos/química , Animais , Cromatografia Líquida de Alta Pressão , Ácidos Graxos/química , Malásia , Valor Nutritivo , Proteínas/química
17.
Parasitology ; 146(7): 956-967, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30975235

RESUMO

The essential oil (EO) of Thymus capitatus, seven fractions (F1-F7) obtained from silica gel chromatography, and several pure EO components were evaluated with respect to in vitro activities against Echinococcus multilocularis metacestodes and germinal layer (GL) cells. Attempts to evaluate physical damage in metacestodes by phosphoglucose isomerase (PGI) assay failed because EO and F1-F7 interfered with the PGI-activity measurements. A metacestode viability assay based on Alamar Blue, as well as transmission electron microscopy, demonstrated that exposure to EO, F2 and F4 impaired metacestode viability. F2 and F4 exhibited higher toxicity against metacestodes than against mammalian cells, whereas EO was as toxic to mammalian cells as to the parasite. However, none of these fractions exhibited notable activity against isolated E. multilocularis GL cells. Analysis by gas chromatography-mass spectrometry showed that carvacrol was the major component of the EO (82.4%), as well as of the fractions F3 (94.4%), F4 (98.1%) and F5 (90.7%). Other major components of EO were ß-caryophyllene, limonene, thymol and eugenol. However, exposure of metacestodes to these components was ineffective. Thus, fractions F2 and F4 of T. capitatus EO contain potent anti-echinococcal compounds, but the activities of these two fractions are most likely based on synergistic effects between several major and minor constituents.


Assuntos
Anti-Helmínticos/farmacologia , Echinococcus multilocularis/citologia , Echinococcus multilocularis/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Thymus (Planta)/química , Animais , Anti-Helmínticos/química , Bioensaio , Carcinoma Hepatocelular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cromatografia em Gel , Descoberta de Drogas , Equinococose/tratamento farmacológico , Fibroblastos/efeitos dos fármacos , Prepúcio do Pênis/citologia , Prepúcio do Pênis/efeitos dos fármacos , Humanos , Masculino , Óleos Voláteis/química , Óleos de Plantas/química , Ratos
18.
Bioorg Chem ; 92: 103270, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31539749

RESUMO

2-substitued-benzopyrimidinones 2 were synthesized in high to excellent yields in a single step via condensation of 2-aminobenzamide 1 with some aryl-aldehydes in the presence of iodine. Cyclocondensation reaction of hydrazides 3 which were obtained in two steps from benzopyrimidinones 2, with some electrophilic species such as 2,4-pentandione, 2,5-hexandione, 1-phenylbutan-1,3-dione and cyclic anyhdrides provided the new compounds 4a-c, 5a-c, 6a-c, 7a-c, 8a-c and 9a-c. The synthesized compounds were characterized by spectroscopic means. They were also evaluated for their anti-tyrosinase potential. The structure-activity relationship (SAR) was discussed on the basis of the molecular docking analysis.


Assuntos
Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Pirimidinonas/farmacologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Estrutura Molecular , Monofenol Mono-Oxigenase/metabolismo , Pirimidinonas/síntese química , Pirimidinonas/química , Relação Estrutura-Atividade
19.
Bioorg Chem ; 82: 129-138, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30312868

RESUMO

Pyrimidine-fused compounds are of great interest for the discovery of potent bioactive agents. This study describes the synthesis of novel pyranopyrimidines 3a-f and pyranotriazolopyrimidines 4a-d derivatives via the cyclocondensation reaction of α-functionalized iminoether 2, which was obtained from 2-amino-3-cyanopyrane 1, with a series of primary aromatic amines and hydrazides, respectively. Structures of all synthesized compounds were established on the basis of spectroscopic methods including 1H NMR, 13C NMR and ES-HRMS. They were finally tested for their anticoagulant and anti-tyrosinase activities. Significant results have been obtained and the structure-activity relationship (SAR) was discussed with the help of molecular docking analysis.


Assuntos
Anticoagulantes/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Piranos/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Agaricus/enzimologia , Anticoagulantes/sangue , Anticoagulantes/síntese química , Anticoagulantes/química , Sítios de Ligação , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/química , Tempo de Tromboplastina Parcial , Piranos/sangue , Piranos/síntese química , Piranos/química , Pirimidinas/sangue , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade , Triazóis/sangue , Triazóis/síntese química , Triazóis/química
20.
Bioorg Chem ; 89: 103009, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31158579

RESUMO

A new series of 3-hydroxyflavones (1-46) were synthesized according to the Claisen-Schmidt followed by Algar-Flynn-Oyamada reactions (AFO) in one step. The synthesized flavonoids were characterized by 1H NMR, 13C NMR and DCI-HRMS. All the synthesized compounds were tested in vitro for their 15-lipoxygenase inhibitory and cytotoxic activity against the human cell lines HCT-116 (Human colon carcinoma), IGROV-1 and OVCAR-3 (human ovarian carcinoma). It has been found that the derivatives 25, 37 and 45 were the most actives against HCT-116 (IC50 = 8.0, 9.0 and 9.0 µM, respectively) and against IGROV-1 (IC50 = 2.4, 5.0 and 6.0 µM, respectively). The derivatives 14 and 21 exhibited the higher anti-inflammatory activity at 100 µM with PI values of 76.50 and 72.70%, respectively. Molecule description was performed with DFT calculations, the drug likeness and bioactivity scores. The results exhibted that some compounds are in linear correlation with Lipinski's rule of five showing good drug likeness and bioactivity score for drug targets.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Araquidonato 15-Lipoxigenase/metabolismo , Flavonoides/farmacologia , Inibidores de Lipoxigenase/farmacologia , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Teoria da Densidade Funcional , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/síntese química , Flavonoides/química , Células HCT116 , Humanos , Inibidores de Lipoxigenase/síntese química , Inibidores de Lipoxigenase/química , Estrutura Molecular , Relação Estrutura-Atividade
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