RESUMO
Monitoring pharmaceutical drugs in various mediums is crucial to mitigate adverse effects. This study presents a chemical sensor using an oval-like zinc oxide (ZnO) nanostructure for electrochemical detection of nalbuphine. The ZnO nanostructure, produced via an efficient sol-gel technique, was extensively characterized using field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-visible spectrophotometry, and fourier transform infrared spectroscopy (FTIR). A slurry of the ZnO nanostructure in a binder was applied to a glassy carbon electrode (GCE). The sensor's responsiveness to nalbuphine was assessed using linear sweep voltammetry (LSV), achieving optimal performance by fine-tuning the pH. The sensor demonstrated a proportional response to nalbuphine concentrations up to 150.0 nM with a good regression coefficient (R2) and a detection limit of 6.20 nM (S/N ratio of 3). Selectivity was validated against various interfering substances, and efficacy was confirmed through real sample analysis, highlighting the sensor's successful application for nalbuphine detection.
Assuntos
Técnicas Eletroquímicas , Eletrodos , Nalbufina , Nanoestruturas , Óxido de Zinco , Óxido de Zinco/química , Nalbufina/análise , Técnicas Eletroquímicas/métodos , Nanoestruturas/química , Limite de DetecçãoRESUMO
In this article, a new series of 2-((3,5-disubstituted-2-thioxo-imidazol-1-yl)imino)acenaphthylen-1(2H)-ones were synthesized. Imidazole-2-thione with acenaphthylen-one gave a hybrid scaffold that integrated key structural elements essential for DNA damage via direct DNA intercalation and inhibition of the topoisomerase II enzyme. All the synthesized compounds were screened to detect their DNA damage using a terbium fluorescent probe. Results demonstrated that 4-phenyl-imidazoles 5b and 5e in addition to 4-(4-chlorophenyl)imidazoles 5h and 5j would induce detectable potent damage in ctDNA. The four most potent compounds as DNA intercalators were further evaluated for their antiproliferative activity against HepG2, MCF-7 and HCT-116 utilizing the MTT assay. The highest anticancer activity was recorded with compounds 5b and 5h against the breast cancer cell line MCF-7 which were 1.5- and 3- folds more active than doxorubicin, respectively. Therefore, imidazole-2-thione tethered acenaphthylenone derivatives can be considered as promising scaffold for the development of effective dual DNA intercalators and topoisomerase II inhibitors.
Assuntos
Antineoplásicos , Inibidores da Topoisomerase II , Inibidores da Topoisomerase II/farmacologia , Inibidores da Topoisomerase II/química , Relação Estrutura-Atividade , Substâncias Intercalantes/farmacologia , Tionas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Imidazóis/farmacologia , DNA , Apoptose , Simulação de Acoplamento Molecular , DNA Topoisomerases Tipo II/metabolismo , Proliferação de CélulasRESUMO
We herein report the facile synthesis of a series of 3,5-substituted-1,2,4-oxadiazole derivatives 9a-e and 10a-e in good to excellent yields by employing NMI-MsCl mediated amide bond formation reaction. The anti-inflammatory potential of the newly synthesized compounds were evaluated by anti-denaturation assay using diclofenac sodium as the reference drug. The compounds 9a and 9d demonstrated promising activity profile when compared to the reference standard. The SAR and molecular docking studies were also carried out for obtaining more details about the profound activity profile of the synthesized molecules. The synthesized compounds were docked against two target proteins TGF-ß and IL-1 by AutoDock vina and Auto Dock 4.2.
Assuntos
Anti-Inflamatórios , Oxidiazóis , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Oxidiazóis/farmacologia , Oxidiazóis/química , Anti-Inflamatórios/farmacologia , AmidasRESUMO
We herein report the facile synthesis of a series of 3,5-substituted-1,2,4-oxadiazole derivatives in good to excellent yields. The anti-inflammatory potential of the newly synthesized compounds was evaluated by anti-denaturation assay using diclofenac sodium as the reference standard. Some of the compounds exhibited profound activity profile when compared to the standard drug. The molecular docking and SAR studies were carried out at the later stage for gaining more insights about the promising activity profile of the synthesized molecules.
Assuntos
Anti-Inflamatórios , Diclofenaco , Anti-Inflamatórios/farmacologia , Diclofenaco/farmacologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Oxidiazóis/farmacologia , Piperazinas , Relação Estrutura-AtividadeRESUMO
We herein report a modified methodology for the synthesis of some oxadiazoles linked to amides under mild conditions. The developed protocol using NMI-TfCl has been found to be effective and tolerant for the amide bond formation reaction of a series of electronically deactivating and sterically challenging amines. The antioxidant potential of the newly synthesized compounds has been evaluated at the later stage.
Assuntos
Aminas , Oxidiazóis , Amidas/química , Aminas/química , Oxidiazóis/químicaRESUMO
Antimicrobial resistance has posed a serious health concern worldwide, which is mainly due to the excessive use of antibiotics. In this study, gold nanoparticles synthesized from the plant Tinospora cordifolia were used against multidrug-resistant Pseudomonas aeruginosa. The active components involved in the reduction and stabilization of gold nanoparticles were revealed by gas chromatography-mass spectrophotometry(GC-MS) of the stem extract of Tinospora cordifolia. Gold nanoparticles (TG-AuNPs) were effective against P. aeruginosa at different concentrations (50,100, and 150 µg/mL). TG-AuNPs effectively reduced the pyocyanin level by 63.1% in PAO1 and by 68.7% in clinical isolates at 150 µg/mL; similarly, swarming and swimming motilities decreased by 53.1% and 53.8% for PAO1 and 66.6% and 52.8% in clinical isolates, respectively. Biofilm production was also reduced, and at a maximum concentration of 150 µg/mL of TG-AuNPs a 59.09% reduction inPAO1 and 64.7% reduction in clinical isolates were observed. Lower concentrations of TG-AuNPs (100 and 50 µg/mL) also reduced the pyocyanin, biofilm, swarming, and swimming. Phenotypically, the downregulation of exopolysaccharide secretion from P. aeruginosa due to TG-AuNPs was observed on Congo red agar plates.
Assuntos
Nanopartículas Metálicas , Pseudomonas aeruginosa , Ouro/farmacologia , Piocianina/farmacologia , Biofilmes , Antibacterianos/farmacologiaRESUMO
In this paper, we report on the design and synthesis of a novel series of quinazoline-2,4(1H,3H)-dione derivatives as fluoroquinolone-like inhibitors of bacterial gyrase and DNA topoisomerase IV to identify and develop antimicrobial agents to prevent bacterial resistance problems. Their structures were confirmed using spectroscopic analyses (IR, NMR, and EI-MS). The novel quinazoline-2,4(1H,3H)-dione derivatives were evaluated for their antimicrobial activities against Gram-positive and Gram-negative bacterial strains using the Agar well diffusion method to study the antimicrobial activities and compared them with the standard drugs. Most compounds displayed moderate activity. Among the tested compounds, the most promising compounds 13 and 15 provided broad bioactive spectrum against Gram-positive and Gram-negative strains compared to the standard drugs.
Assuntos
Antibacterianos , Anti-Infecciosos , Antibacterianos/química , Anti-Infecciosos/farmacologia , Bactérias Gram-Negativas , Testes de Sensibilidade Microbiana , Quinazolinas/química , Relação Estrutura-AtividadeRESUMO
Studies of a catalytic asymmetric version of the Matteson reaction between dichloromethylboronates and organolithium reagents have been undertaken. From several different chiral catalytic systems studied, only one based on a mannitol derivative has given substantial asymmetric induction close to that previously achieved with a bis(oxazoline) derivative and ytterbium triflate. More detailed study of the latter reaction revealed that fresh ytterbium triflate actually reduced the level of asymmetric induction, while "aged" ytterbium triflate, or a fresh sample that had been treated with water, brought about improved induction. The implications of these findings are discussed.
RESUMO
New hydrazinecarbothioamides with a phenylsulfonyl group were synthesized and their structures were identified by different spectroscopic data (1 H NMR, 13 C NMR, two-dimensional NMR, mass spectrometry, elemental analysis, and single-crystal X-ray analysis). The mechanism describing the formation of the products was also discussed. The antidiabetic activity of the isolated products was investigated histochemically. The synthesized sulfonylalkylthiosemicarbazide exhibited antihyperglycemic activity in streptozotocin-induced diabetic mice. Compounds 5a and 5c significantly lowered the blood glucose level to 103.3 ± 1.8 and 102 ± 3.9 mg/dl, respectively. Also, they caused a significant decrease in malondialdehyde levels and normalized the glutathione levels in streptozotocin-induced diabetic mice, compared with the diabetic group. The results suggest that the synthesized hydrazinocarbothioamides may effectively inhibit the development of oxidative stress in diabetes.
Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Desenho de Fármacos , Hidrazinas/farmacologia , Hipoglicemiantes/farmacologia , Tioamidas/farmacologia , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Relação Dose-Resposta a Droga , Hidrazinas/síntese química , Hidrazinas/química , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Masculino , Camundongos , Estrutura Molecular , Estresse Oxidativo/efeitos dos fármacos , Estreptozocina , Relação Estrutura-Atividade , Tioamidas/síntese química , Tioamidas/químicaRESUMO
We report herein a new series of synthesized N-substituted-2-quinolonylacetohydrazides aiming to evaluate their activity towards SARS-CoV-2. The structures of the obtained products were fully confirmed by NMR, mass, IR spectra and elemental analysis as well. Molecular docking calculations showed that most of the tested compounds possessed good binding affinity to the SARS-CoV-2 main protease (Mpro) comparable toRemdesivir.
RESUMO
Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities; however, few have dealt with the chemistry and the biology of heteroannulated derivatives. Therefore, we focused our attention on recent topics, up until 2020, for the synthesis of pyrazoles, their heteroannulated derivatives, and their applications as biologically active moieties. Moreover, we focused on traditional procedures used in the synthesis of pyrazoles.
Assuntos
Pirazóis/síntese química , Pirazóis/farmacologia , Técnicas de Química Sintética , Humanos , Pirazóis/químicaRESUMO
A series of novel 1,2,3-triazoles hybridized with two quinolin-2-ones, was designed and synthesized through click reactions. The structures of the synthesized compounds were elucidated by NMR, IR, and mass spectra in addition to elemental analysis. The synthesized compounds were assessed for their antiapoptotic activity in testis, as testicular torsion is the main cause of male infertility. This effect was studied in light of decreasing tissue damage induced by I/R in the testis of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Compounds 6a-c were the most active antiapoptotic hybrids with significant measurements for malondialdehyde (MDA) and total antioxidant capacity (TAC) and the apoptotic biomarkers (testicular testosterone, TNFα, and caspase-3) in comparison to the reference. A preliminary mechanistic study was performed to improve the antiapoptotic activity through caspase-3 inhibition. A compound assigned as 6-methoxy-4-(4-(((2-oxo-1,2-dihydroquinolin-4-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)quinolin-2(1H)-one (6c) was selected as a representative of the most active hybrids in comparison to NAC. Assay of cytochrome C for 6c revealed an attenuation of cytochrome C level about 3.54 fold, comparable to NAC (4.13 fold). In caspases-3,8,9 assays, 6c was found to exhibit more potency and selectivity toward caspase-3 than other caspases. The testicular histopathological investigation was carried out on all targeted compounds 6a-g, indicating a significant improvement in the spermatogenesis process for compounds 6a-c if compared to the reference relative to the control. Finally, molecular docking studies were done at the caspase-3 active site to suggest possible binding modes. Hence, it could conceivably be hypothesized that compounds 6a-c could be considered good lead candidate compounds as antiapoptotic agents.
Assuntos
Apoptose/efeitos dos fármacos , Caspase 3 , Inibidores de Caspase , Desenho de Fármacos , Simulação de Acoplamento Molecular , Quinolonas , Triazóis , Animais , Caspase 3/química , Caspase 3/metabolismo , Inibidores de Caspase/síntese química , Inibidores de Caspase/química , Inibidores de Caspase/farmacologia , Quinolonas/síntese química , Quinolonas/química , Quinolonas/farmacologia , Ratos , Triazóis/síntese química , Triazóis/química , Triazóis/farmacologiaRESUMO
We have developed a new idea to synthesize a key intermediate molecule by utilizing deep eutectic solvent (DES) and ultrasound in a multistep reaction to ensure process cost-effectiveness. To confirm the stability of reagents with DES, electronic energies were calculated at the B3LYP/6-31+G(d,p) level of theory. DES stabilized the reagents mainly due to strong intermolecular hydrogen bonding. Key intermediate (3) and final compounds (4a-n) were synthesized in a higher yield of 95% and 80%-88%, respectively. Further, final compounds (4a-n) were assessed for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation. The compounds 4f, 4g, 4j, 4l, and 4m showed good anti-inflammatory activity, while 4f, 4i, and 4n exhibited very good analgesic activity as compared to the standard drug. The ulcerogenicity of selected compounds was far less than the indomethacin. The ligands had also shown a good docking score (4f = -6.859 kcal/mol and 4n = -7.077 kcal/mol) as compared to control indomethacin (-6.109 kcal/mol) against the target protein COX-2. These derivatives have the potential to block this enzyme and can be used as NSAID. The state-of-art DFT theory was used to validate the lipid peroxidation mechanism of the active compounds which was in good agreement with the variations of BDEs and IP of the tested compounds.
Assuntos
Analgésicos , Anti-Inflamatórios não Esteroides , Inibidores de Ciclo-Oxigenase 2 , Ciclo-Oxigenase 2/metabolismo , Indóis , Simulação de Acoplamento Molecular , Analgésicos/síntese química , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Feminino , Indóis/síntese química , Indóis/química , Indóis/farmacologia , Masculino , Camundongos , Relação Estrutura-Atividade , Ondas UltrassônicasRESUMO
Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a-e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c-e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4'-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4'-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4'-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC50 of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proteína Quinase CDC2/antagonistas & inibidores , Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Melanoma/tratamento farmacológico , Naftóis/farmacologia , Tiazóis/química , Antineoplásicos/química , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/química , Humanos , Melanoma/enzimologia , Melanoma/patologia , Simulação de Acoplamento Molecular , Estrutura Molecular , Naftóis/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
In the title compound, C15H12N2S, the methylthioquinazoline group is planar with the methyl C displaced by only 0.116â (3)â Å from the plane of the quinazoline moiety. The dihedral angle between the phenyl ring and the quinazoline ring system is 13.95â (5)°. In the crystal, each molecule is linked by π-π stacking between to two adjacent inversion-related molecules. On one side, the inverted quinazoline groups interact with a centroid-centroid distance of 3.7105â (9)â Å. On the other side, the quinazoline group interacts with the pyrimidine and phenyl rings of the second neighbour with centroid-centroid distances of 3.5287â (8) and 3.8601â (9)â Å, respectively.
RESUMO
In the title compound, C10H10N2S, all non-H atoms are almost coplanar [maximum deviation = 0.103â (1)â Å]. In the crystal, N-Hâ¯S inter-actions form R 2 (2)(8) rings linking pairs of mol-ecules related by inversion. The mol-ecular pairs are stacked along [100]. A herringbone arrangement of pairs in the [010] direction forms layers parallel to (010).
RESUMO
The title compound, C9H8N2O, is almost planar, with the C atom of the meth-oxy group deviating from the mean plane of the quinazoline ring system (r.m.s. deviation = 0.011â Å) by 0.068â (4)â Å. In the crystal, mol-ecules form π-π stacks parallel to the b-axis direction [centroid-centroid separation = 3.5140â (18)â Å], leading to a herringbone packing arrangement.
RESUMO
In the title compound, C22H28N2, the dihedral angle between the planes of the phenyl ring and the di-hydro-quinazoline ring system (r.m.s. deviation = 0.030â Å) is 24.95â (7)° and both n-butane chains assume all-trans conformations. In the crystal, N-Hâ¯N hydrogen bonds link the mol-ecules into C(4) chains propagating in the [001] direction.
RESUMO
This study highlights the effectiveness of oyster shell biocomposite for the biosorption of Cd(II) and Pb(II) ions from an aqueous solution. The aim of this work was to modify a novel biocomposite derived from oyster shell for the adsorption of Cd(II) and Pb(II) ions from aqueous solution. The studied revealed the specific surface BET surface area was 9.1476 m2/g. The elemental dispersive x-ray analysis (EDS) indicated that C, O, Ag, Ca were the predominant elements on the surface of the biocomposite after which metals ions of Cd and Pb were noticed after adsorption. The Fourier transform Irradiation (FT-IR) revealed the presence of carboxyl and hydroxyl groups on the surface. The effect of process variables on the adsorption capacity of the modified biocomposite was examined using the central composite design (CCD) of the response surface methodology (RSM). The process variables which include pH, adsorbent dose, the initial concentration and temperature were the most effective parameters influencing the uptake capacity. The optimal process conditions of these parameters were found to be pH, 5.57, adsorbent dose, 2.53 g/L, initial concentration, 46.76 mg/L and temperature 28.48°C for the biosorption of Cd(II) and Pb(II) ions from aqueous solution at a desirability coefficient of 1. The analysis of variance (ANOVA) revealed a high coefficient of determination (R2 > 0.91) and low probability coefficients for the responses (P < 0.05) which indicated the validity and aptness of the model for the biosorption of the metal ions. Experimental isotherm data fitted better to the Langmuir model and the kinetic data fitted better to the pseudo-second-order model. Maximun Cd(II) and Pb(II) adsorption capacities of the oyster shell biocomposite were 97.54 and 78.99 mg/g respectively and was obtained at pH 5.56 and 28.48°C. This investigation has provided the possibility of the utilization of alternative biocomposite as a sustainable approach for the biosorption of heavy metal ions from the wastewater stream.
Assuntos
Cádmio , Ostreidae , Animais , Cádmio/análise , Espectroscopia de Infravermelho com Transformada de Fourier , Adsorção , Chumbo , ÍonsRESUMO
The structural studies of the fluorinated Schiff base ligand and its copper complex were synthesized and characterized by Fourier transform infrared, UV-visible, and photoluminescence spectroscopy. Single-crystal X-ray diffraction analysis unveils a dinuclear copper complex arising from double bridging acetate anions to copper ions that are chelated by the tridentate Schiff base ligand Cu(LS). The trigonality index τ5 of 0.080 indicates a distorted square pyramidal coordination geometry for the metal. The SL ligand and complex exhibit intra- and intermolecular interactions, leading to unique supramolecular architectures. The structural changes between the free halogenated Schiff base ligand and upon coordination with the metal were extensively studied by experimental and theoretical approaches. The intra- and intermolecular interactions have been analyzed by Hirshfeld surface and quantum theory of atoms in molecules analysis, and the enrichment ratio highlights the most favored interactions in the formation of molecular packing. The chemical and physical properties, such as the HOMO - LUMO energy gap, chemical reactivity, and electron density topology, are studied using density functional theory studies. In addition, the Schiff base ligand compound is used to study the latent fingerprint analysis.