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1.
BMC Complement Med Ther ; 24(1): 157, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38609946

RESUMEN

BACKGROUND: Oral bacterial infections are difficult to treat due to emergence of resistance against antibiotic therapy. Essential oils are considered emerging alternate therapy against bacterial infections and biofilms. We investigated Citrus bergemia flower essential oil against oral pathogens. METHODS: The essential oil was analsyed using Gas Chromatography(GC-MS), in silico investigations, antioxidant, antimicrobial, antibiofilm and antiquorum sensing assays. RESULTS: Gas Chromatography analysis confirmed presence of 17 compounds including 1,6-Octadien-3-ol,3,7-dimethyl, 48.17%), l-limonene (22.03%) and p-menth-1-ol, 8-ol (7.31%) as major components. In silico analysis showed compliance of all tested major components with Lipinski's rule, Bioavailability and antimicrobial activity using PASS (prediction of activity spectrum of substances). Molecular docking with transcriptional regulators 3QP5, 5OE3, 4B2O and 3Q3D revealed strong interaction of all tested compounds except 1,6-Octadien-3-ol,3,7-dimethyl. All tested compounds presented significant inhibition of DPPH (2,2-diphenyl-1-picrylhydrazyl) (IC50 0.65 mg/mL), H2O2 (hydrogen peroxide) (63.5%) and high FRAP (ferrous reducing antioxidant power) value (239.01 µg). In antimicrobial screening a significant activity (MIC 0.125 mg/mL) against Bacillus paramycoides and Bacillus chungangensis was observed. Likewise a strong antibiofilm (52.1 - 69.5%) and anti-QS (quorum sensing) (4-16 mm) activity was recorded in a dose dependent manner. CONCLUSION: It was therefore concluded that C. bergemia essential oil posess strong antioxidant, antimicrobial and antibiofilm activities against tested oral pathogens.


Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Citrus , Aceites Volátiles , Antioxidantes/farmacología , Peróxido de Hidrógeno , Simulación del Acoplamiento Molecular , Aceites Volátiles/farmacología , Antiinfecciosos/farmacología , Flores
2.
Front Med (Lausanne) ; 10: 1242939, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37964879

RESUMEN

Aims: To investigate the biochemical correlation of hemoglobin (Hb), dyslipidemia, and HbA1c with gestational diabetes mellitus (GDM). Background: GDM is a condition that develops during pregnancy and is characterized by high blood sugar levels. Biochemical parameters such as hemoglobin (Hb), dyslipidemia, and HbA1c have been implicated in the development of GDM. Understanding the correlation between these biochemical parameters and GDM can provide insights into the underlying mechanisms and potential diagnostic markers for the condition. Objective: The objective of this study was to evaluate the correlation of various biochemical parameters, including Hb, dyslipidemia, and HbA1c, in pregnant women with and without GDM. Method: A cross-sectional study design was used. Pregnant females attending a tertiary care hospital in Faisalabad between September 1st, 2021, and June 25th, 2022, were included in the study. The participants were divided into two groups: those with GDM (GDM group) and those without GDM (non-GDM group). Blood glucose, Hb, and lipid levels were compared between the two groups using statistical tests, including chi-square, independent sample t-test, and Pearson's correlation. Result: Out of the 500 participants, 261 were in the 2nd trimester and 239 in the 3rd trimester. Maternal age showed a significant difference between the GDM and non-GDM groups. The levels of Hb, TC, HDL, LDL, and HbA1c significantly differed (p < 0.05) between the two groups. TC (r = 0.397), TG (r = 0.290), and LDL (r = 0.509) showed a statistically significant and moderately positive correlation with GDM. HDL (r = -0.394) and Hb (r = -0.294) showed a moderate negative correlation with GDM. Conclusion: Increased levels of HbA1c, TC, and LDL, along with decreased levels of HDL and Hb, were identified as contributing factors to GDM. The levels of TC, TG, and LDL were positively correlated with GDM, while HDL and Hb were negatively correlated. The findings of this study suggest that monitoring and managing hemoglobin, dyslipidemia, and HbA1c levels during pregnancy may be important in identifying and potentially preventing or managing GDM. Further research is needed to explore the underlying mechanisms and potential interventions targeting these biochemical parameters in relation to GDM.

3.
Future Med Chem ; 15(23): 2181-2194, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37997685

RESUMEN

Background: DNA gyrase and urease enzymes are important targets for the treatment of gastroenteritis, appendicitis, tuberculosis, urinary tract infections and Crohn's disease. Materials & methods: Esterification of norfloxacin was performed to enhance DNA gyrase and urease enzyme inhibition potential. Structure elucidation and chemical characterization were done through spectral (1H NMR, Fourier transform IR, 13C NMR) and carbon, hydrogen, nitrogen and sulfur analysis along with molecular docking. Results & conclusion: The majority of derivatives exhibited significant results but the 3e derivative showed maximum bactericidal, DPPH scavenging (96%), DNA gyrase and urease enzyme inhibitory activity with IC50 of 0.15 ± 0.24 and 1.14 ± 0.11 µM respectively which was further supported by molecular docking studies. So, the active derivatives can serve as a lead compound for the treatment of various pathological conditions.


Asunto(s)
Girasa de ADN , Norfloxacino , Simulación del Acoplamiento Molecular , Norfloxacino/farmacología , Girasa de ADN/metabolismo , Ureasa/química , Ureasa/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Relación Estructura-Actividad , Estructura Molecular
4.
Front Chem ; 11: 1065986, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36909711

RESUMEN

Introduction: The area of "Green Synthesis of Nano-medicine," as compared to its synthetic counterparts, is a relatively safer research technology for various biomedical applications, including identification, therapeutic application, and prevention of pathological conditions, pain control, safety, and development of human wellness. The present study explored the synthesis and characterization of AgNPs using the ethanolic extract of Piper cubeba fruit as a reducing and stabilizing agent and its potential as an enzyme inhibitory agent. Urease inhibitors are helpful against many severe diseases, including gastric ulcers induced by Helicobacter pylori. Method: The fruits of the Piper cubeba plant were taken and ground to a fine powder. Plant material was added to 500 ml ethanol, and the mixture was filtered. The solvent of the filtrate was evaporated, and a thick, gummy extract was obtained and stored at 4°C in the refrigerator. AgNPs were green synthesized from solutions of AgNO3 using the P. cubeba extract, which was indicated by a change in the color from light brown to deep brown. The synthesized AgNPs were characterized via Ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and scanning electron microscopy (SEM). Results and Discussion: Analysis showed the reduction of Ag+ to Ag0 at room temperature (25°C), and the average particle size of AgNPs was in the range of 40-80 nm. Consequently, the synthesized AgNPs were evaluated for their anti-urease activity. The maximum urease inhibition of the Piper cubeba ethanolic extract was 88.5% at 5 mg conc., and of derived nanoparticles was 78.6% at 0.05 mg conc. The results were nearly similar to the control drug, i.e., thiourea (0.5 and 0.6 mM conc., respectively). Conclusion: The study concluded that the P. cubeba extract, as well as its green-derived AgNPs, might prove to be a better and safer substitute for their enzyme inhibitory potential in emerging medicine and novel drug delivery techniques to improve and maintain human health.

5.
Molecules ; 28(4)2023 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-36838897

RESUMEN

This study aimed to evaluate 2-(N-((2'-(2H-tetrazole-5-yl)-[1,1'-biphenyl]-4yl)-methyl)-pentanamido)-3-methyl butanoic acid-based ester derivatives as a new class of angiotensin-II receptor antagonists. For this purpose, a series of compounds were synthesized using a variety of phenols. Their chemical characterization was established by FTIR, 1HNMR, and 13CNMR techniques. The biological activities including antioxidant potentials using the DPPH assay, the antihypertensive assay, the urease enzyme inhibition assay, and the antibacterial assay using agar well diffusion methods were performed. All the new compounds showed significant free radical scavenging potentials more than the parent drug while retaining antihypertensive potentials along with urease inhibition properties. However, the AV2 test compound was found to be the most potent against hypertension. Most of the synthesized analogs showed urease inhibitory actions. Molecular docking studies were performed for all the active analogs to decode the binding detail of the ligands with receptors of the enzyme's active site.


Asunto(s)
Antihipertensivos , Ureasa , Ácido Butírico , Simulación del Acoplamiento Molecular , Tetrazoles , Relación Estructura-Actividad
6.
Molecules ; 28(3)2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36771070

RESUMEN

The current study was designed to synthesize, characterize, and screen the molecular and biological activities of different metformin derivatives that possess potent antidiabetic potential with minimal side-effects. Metformin-based derivatives containing the metal complexes Cu II (MCu1-MCu9) and Zn II (MZn1-MZn9) were generated using aromatic aldehydes and ketones in a template process. The novel metal complexes were characterized through elemental analysis, physical state, melting point, physical appearance, Fourier-transform infrared (FTIR) spectroscopy, UV/visible (UV/Vis) spectroscopy, 1H nuclear magnetic resonance (NMR) spectroscopy, and 13C-NMR spectroscopy. Screening for inhibitory activity against the enzymes α-amylase and α-glucosidase, and molecular simulations performed in Schrödinger were used to assess the synthesized derivatives' biological potential. Met1, Met2, Met3, and Met8 all displayed activities that were on par with the reference in an enzymatic inhibition assay (amylase and glucosidase). The enzyme inhibition assay was corroborated by molecular simulation studies, which also revealed a competitive docking score compared to the gold standard. The Swiss ADME online web server was utilized to compute ADME properties of metformin analogues. Lipinski's rule of five held true across all derivatives, making it possible to determine the percentage of absorption. Metformin derivatives showed significant antidiabetic activities against both targeted enzymes, and the results of this work suggest that these compounds could serve as lead molecules for future study and development.


Asunto(s)
Complejos de Coordinación , Metformina , Cobre/química , Metformina/farmacología , Zinc/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/química , Simulación del Acoplamiento Molecular , Hipoglucemiantes/farmacología , Hipoglucemiantes/química , Espectroscopía Infrarroja por Transformada de Fourier , alfa-Glucosidasas/química
7.
PLoS One ; 17(12): e0278684, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36574404

RESUMEN

The goal of the current work was to create structural analogues of a beta lactam antibiotic that might be possibly effective against bacterial resistant strains. FTIR, 1H NMR, 13C NMR, and CHNS analyses were used to perform the spectroscopic study on the compounds M1-8. The effects of the aforementioned substances on gram-positive and gram-negative bacterial strains were investigated. Most of the eight compounds had antibacterial activity that was lower than or equivalent to that of the original medication, but two molecules, M2 and M3, surprisingly, had stronger antibacterial activity. The findings of synthesized analogues against alpha-glucosidase and DPPH inhibition were found to be modest, whereas M2, M3, and M7 strongly inhibited the urease. To comprehend the potential mode of action, a molecular docking research was conducted against urease and -amylase. The research may help in the quest for novel chemical compounds that would be effective against bacteria that are resistant to antibiotics.


Asunto(s)
Ácidos Carboxílicos , Ureasa , Simulación del Acoplamiento Molecular , Ácidos Carboxílicos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Bacterias , Pruebas de Sensibilidad Microbiana , Relación Estructura-Actividad
8.
Heliyon ; 8(11): e11332, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36387450

RESUMEN

Synthesis of new Cefpodoxime derivatives via Schiff Bases mechanism and the efficiency of their antimicrobial and antiviral activities were addressed. They were analyzed for structural validation by using spectroscopic techniques using FTIR, 1HNMR, and 13CNMR. Molecular docking against IBV Virus papain-like protease (PLPro) was done with Auto dock tools against compounds having excellent IC50 values against IBV (Corona Class) virus. All derivatives showed strong zone of inhibition ranges from (55 ± 2.0 to 70 ± 0.8 mm) against E. coli. Compounds 1,2,4 and 6 derivatives showed remarkable activity against Stenotrophomonas maltophilia and Serratia marcescens. But For most the newly synthesized derivatives C 1 (64 ± 1.60), C 3 (32 ± 0.80), and C 8 (64 ± 1.60) showed potential IC50 values against two variants of Corona class viruses i.e. Avian Influenza (H9) and Avian corona (IBV) viruses. The current study revealed that newly synthesized Schiff Bases possessed strong anti-viral potential. Further studies may make a breakthrough in medical sciences to tackle latest challenges such as Corona Virus Diseases.

9.
Molecules ; 27(19)2022 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-36235221

RESUMEN

Verbena officinalis L. is a traditionally important medicinal herb that has a rich source of bioactive phytoconstituents with biological benefits. The objective of this study was to assess the metabolic profile and in vitro biological potential of V. officinalis. The bioactive phytoconstituents were evaluated by preliminary phytochemical studies, estimation of polyphenolic contents, and gas chromatography-mass spectrometry (GC-MS) analysis of all fractions (crude methanolic, n-hexane, ethyl acetate, and n-butanol) of V. officinalis. The biological investigation was performed by different assays including antioxidant assays (DPPH, ABTS, CUPRAC, and FRAP), enzyme inhibition assays (urease and α-glucosidase), and hemolytic activity. The ethyl acetate extract had the maximum concentration of total phenolic and total flavonoid contents (394.30 ± 1.09 mg GAE·g-1 DE and 137.35 ± 0.94 mg QE·g-1 DE, respectively). Significant antioxidant potential was observed in all fractions by all four antioxidant methods. Maximum urease inhibitory activity in terms of IC50 value was shown by ethyl acetate fraction (10 ± 1.60 µg mL-1) in comparison to standard hydroxy urea (9.8 ± 1.20 µg·mL-1). The n-hexane extract showed good α-glucosidase inhibitory efficacy (420 ± 20 µg·mL-1) as compared to other extract/fractions. Minimum hemolytic activity was found in crude methanolic fraction (6.5 ± 0.94%) in comparison to positive standard Triton X-100 (93.5 ± 0.48%). The GC-MS analysis of all extract/fractions of V. officinalis including crude methanolic, n-hexane, ethyl acetate, and n-butanol fractions, resulted in the identification of 24, 56, 25, and 9 bioactive compounds, respectively, with 80% quality index. Furthermore, the bioactive compounds identified by GC-MS were analyzed using in silico molecular docking studies to determine the binding affinity between ligands and enzymes (urease and α-glucosidase). In conclusion, V. officinalis possesses multiple therapeutical potentials, and further research is needed to explore its use in the treatment of chronic diseases.


Asunto(s)
Antioxidantes , Verbena , 1-Butanol , Acetatos , Antioxidantes/química , Flavonoides/química , Cromatografía de Gases y Espectrometría de Masas , Hexanos , Ligandos , Metanol/química , Simulación del Acoplamiento Molecular , Octoxinol/análisis , Fitoquímicos/química , Fitoquímicos/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Urea/análisis , Ureasa , alfa-Glucosidasas
10.
Biochem J ; 479(19): 2035-2048, 2022 10 14.
Artículo en Inglés | MEDLINE | ID: mdl-36111588

RESUMEN

In the present work, we reported the synthesis of Schiff bases from 4-phenoxy-5-sulfamoylbenzoic acid motif. The reaction was carried out by substitution of different aldehyde and ketones at sulfamoyl group of sulfamoylbenzoic acid. The generated substituted products (4a-4i) possessed potent structure activity relationship and exhibited drug like properties. The structures of synthesized compounds were characterized on the basis of FT-IR, 1H NMR, 13C NMR and mass spectroscopic data. The effects of synthesized products were investigated on urease enzyme through anti-urease enzyme inhibition assay (Weather burn method). These compounds were further evaluated for antibacterial potential. The Rationale behind the assessment of antibacterial activity was to investigate the synthesized compound's dual mode action against urease and virulent bacterial strains in order to develop a lead candidate for the treatment of GIT diseases such as gastric and peptic ulcers, as well as hepatic encephalopathy. The synthesized derivatives have outstanding anti-urease and antibacterial action, as is evident from in vitro and in silico studies. As a result, these compounds (3-(butylamino)-4-phenoxy-5-sulfamoylbenzoic acid; 4a-4i) might be explored further as a potential lead for the development of potent inhibitors in the future.


Asunto(s)
Bases de Schiff , Ureasa , Aldehídos , Antibacterianos/farmacología , Bacterias/metabolismo , Benzoatos , Colorantes/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Cetonas/farmacología , Simulación del Acoplamiento Molecular , Estructura Molecular , Bases de Schiff/química , Espectroscopía Infrarroja por Transformada de Fourier , Relación Estructura-Actividad , Ureasa/química , Ureasa/metabolismo
11.
Molecules ; 27(18)2022 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-36144585

RESUMEN

This work was undertaken to explore the phytochemical composition, antioxidant, and enzyme-inhibiting properties of Neurada procumbens L. extracts/fractions of varying polarity (methanol extract and its fractions including n-hexane, chloroform, n-butanol, and aqueous fractions). A preliminary phytochemical study of all extracts/fractions, HPLC-PDA polyphenolic quantification, and GC-MS analysis of the n-hexane fraction were used to identify the phytochemical makeup. Antioxidant (DPPH), enzyme inhibition (against xanthine oxidase, carbonic anhydrase, and urease enzymes), and antibacterial activities against seven bacterial strains were performed for biological investigation. The GC-MS analysis revealed the tentative identification of 22 distinct phytochemicals in the n-hexane fraction, the majority of which belonged to the phenol, flavonoid, sesquiterpenoid, terpene, fatty acid, sterol, and triterpenoid classes of secondary metabolites. HPLC-PDA analysis quantified syringic acid, 3-OH benzoic acid, t-ferullic acid, naringin, and epicatechin in a significant amount. All of the studied extracts/fractions displayed significant antioxidant capability, with methanol extract exhibiting the highest radical-scavenging activity, as measured by an inhibitory percentage of 81.4 ± 0.7 and an IC50 value of 1.3 ± 0.3. For enzyme inhibition experiments, the n-hexane fraction was shown to be highly potent against xanthine oxidase and urease enzymes, with respective IC50 values of 2.3 ± 0.5 and 1.1 ± 0.4 mg/mL. Similarly, the methanol extract demonstrated the strongest activity against the carbonic anhydrase enzyme, with an IC50 value of 2.2 ± 0.4 mg/mL. Moreover, all the studied extracts/fractions presented moderate antibacterial potential against seven bacterial strains. Molecular docking of the five molecules ß-amyrin, campesterol, ergosta-4,6,22-trien-3ß-ol, stigmasterol, and caryophyllene revealed the interaction of these ligands with the investigated enzyme (xanthine oxidase). The results of the present study suggested that the N. procumbens plant may be evaluated as a possible source of bioactive compounds with multifunctional therapeutic applications.


Asunto(s)
Anhidrasas Carbónicas , Catequina , Plantas Medicinales , Triterpenos , 1-Butanol , Antibacterianos/farmacología , Antioxidantes/química , Ácido Benzoico , Cloroformo , Ácidos Grasos , Flavonoides/análisis , Flavonoides/farmacología , Hexanos , Ligandos , Metabolómica , Metanol/química , Simulación del Acoplamiento Molecular , Fenoles/análisis , Fitoquímicos/análisis , Fitoquímicos/farmacología , Extractos Vegetales/química , Plantas Medicinales/metabolismo , Estigmasterol , Terpenos , Trientina , Ureasa , Xantina Oxidasa
12.
Sci Rep ; 11(1): 18973, 2021 09 23.
Artículo en Inglés | MEDLINE | ID: mdl-34556784

RESUMEN

Current research is based on biology-oriented synthesis of sulphadiazine derivatives and determination of their urease inhibitory activity. In this regard, a series of (E)-4-(benzylideneamino)-N-(pyrimidin-2-yl)benzenesulfonamide was synthesized from sulphadiazine and substituted aromatic aldehydes. The structures of synthesized compounds were ascertained by spectroscopic techniques, such as, FTIR, NMR and HRMS analysis, and in-vitro and in-silico investigation were carried out for the inhibition of urease. Ureases are harmful for humans by producing by-products of urea (ammonia and carbon dioxide). The most active compound (3l) against urease exhibited IC50 value of 2.21 ± 0.45 µM which is 10 times more potent than the standard thiourea (20.03 ± 2.06 µM). It is noteworthy that most of our synthesized compounds showed significant to excellent activities against urease enzyme and most of them substituted by halogen or hydroxy groups at ortho and para positions in their structures. Inhibition of enzyme by the synthesized analogues was in descending order as 3l > 3a > 3b > 3q > 3e > 3o > 3s > 3t > 3g > 3k > 3r > 3f > 3m > 3p > 3n > 3j > 3i > 3h. Moreover, molecular docking studies were performed to rationalize the binding interactions of the synthesized motifs with the active pocket of the urease enzyme. The synthesized sulphadiazine derivatives (3a-u) were found to be non-toxic, and presented passive gastrointestinal absorption.


Asunto(s)
Inhibidores Enzimáticos/síntesis química , Sulfadiazina/síntesis química , Ureasa/antagonistas & inhibidores , Química Farmacéutica , Inhibidores Enzimáticos/farmacología , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Estructura-Actividad , Sulfadiazina/análogos & derivados , Sulfadiazina/farmacología
13.
Inflammopharmacology ; 29(3): 789-800, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34061285

RESUMEN

Sesuvium sesuvioides (Fenzl) Verdc is traditionally used in the treatment of inflammatory diseases such as arthritis and gout The aim of present study was to assess the possible anti-inflammatory, analgesic and antipyretic potential of the methanol extract of Sesuvium sesuvioides (SsCr) to prove scientifically its folklore use in the inflammatory diseases and to screen its total antioxidant capacity by multiple methods and phytocompounds by GC-MS. The preliminary phytochemical studies showed the presence of phenols, flavonoids, glycosides, coumarin, terpenoids, saponins, fats and carbohydrates in crude extract. The total phenolic contents (27.31 ± 0.28 mg GAE/g) and total flavonoids (3.58 ± 0.12 mgRE/g) values were observed. The antioxidant capacity of SsCr showed significant DPPH, ABTS, CUPRAC, FRAP, PBD and metal chelating results. GC-MS analysis displayed the phytoconstituents with anti-inflammatory potentials such as 2-methoxy-4-vinylphenol, vanillin, umbelliferone, methyl ferulate, palmitoleic acid, methyl palmitate and phytol. SsCr presented noteworthy HRBC membrane stability with maximum inhibition of cell hemolysis (47.79%). In carrageenan-induced hind paw edema assay result showed dose-dependent anti-inflammatory action. SsCr presented significant (p < 0.05) analgesic activity in hot-plate and tail flicking tests similarly it also showed the noteworthy inhibition in pain latency against formalin induced analgesia at 1st and 2nd phases. SsCr reduced the acetic acid-induced writhes at different doses (250, 500 and 750 mg). Results of antipyretic activity of SsCr extract were significant at 500 and 750 mg. The results of in vitro and in vivo experimental studies verified the anti-inflammatory, analgesic and antipyretic potential of Sesuvium sesuvioides and supported the folklore uses of this plant.


Asunto(s)
Aizoaceae , Analgésicos/uso terapéutico , Antiinflamatorios/uso terapéutico , Antipiréticos/uso terapéutico , Fitoquímicos/uso terapéutico , Extractos Vegetales/uso terapéutico , Analgésicos/química , Analgésicos/aislamiento & purificación , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Antipiréticos/química , Antipiréticos/aislamiento & purificación , Carragenina/toxicidad , Edema/inducido químicamente , Edema/tratamiento farmacológico , Edema/metabolismo , Femenino , Depuradores de Radicales Libres/aislamiento & purificación , Depuradores de Radicales Libres/farmacología , Depuradores de Radicales Libres/uso terapéutico , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Masculino , Ratones , Dimensión del Dolor/efectos de los fármacos , Dimensión del Dolor/métodos , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Ratas , Ratas Wistar
14.
Bioorg Chem ; 102: 104057, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32663667

RESUMEN

A series of Sulfonamide-based Schiff bases (E)-4-(benzylideneamino)-N-(6-methoxypyridazin-3-yl) benzenesulfonamide (3a-r) targeting Urease Inhibition was synthesized from sulphamethoxy pyridazine and substituted aldehydes. The prepared compounds were characterized by various spectroscopic techniques including FTIR, 1HNMR, 13CNMR, and spectrometric HRMS analysis. The most active agent (3g) bearing halogens and OH groups gave IC50 value of 2.20 µM for urease inhibition against the standard Thiourea (IC50 = 20.03 ± 2.06) and the overall trend within the series was 3g > 3n > 3p > 3j > 3q > 3h, 3o > 3l, 3r > 3k, 3m > 3a > 3d > 3e > 3f. Structure-activity relationship study established that the nature as well as the position of varying groups attached to aryl group had crucial roles in defining the urease inhibition activity. Additionally, in silico investigation was carried out which demonstrated that the compounds exhibit polar and apolar contacts with the crucial residues in the binding site of urease. The ADME analysis suggested all the synthesized compounds to be non-toxic, and likely to undergo passive gastrointestinal absorption. Taken together, the study suggests that the synthesized Sulfonamide-based Schiff bases derivatives may serve as potential hits as urease inhibitors.


Asunto(s)
Simulación del Acoplamiento Molecular/métodos , Bases de Schiff/química , Ureasa/antagonistas & inhibidores , Humanos , Estructura Molecular , Relación Estructura-Actividad
15.
Pak J Pharm Sci ; 33(5(Supplementary)): 2323-2329, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33832907

RESUMEN

Numerous ailments have been effectively treated with natural plants for long time all over the world. Plants provided a back bone for the exploration of novel medicinal compounds. Therefore, chief focus of our study was to isolate the biologically active compounds from the plant source and evaluate their antidiarrheal potentials, as diarrhea is still the most dominant disease in developing countries. The isolation and structure elucidation of two new compounds were identified from methanolic and chloroform extracts of Psidium guajava (guava) leaves. Extracts of plants were acquired by successive maceration from dried powder. Castor oil induced diarrheal-model was used to evaluate the antidiarrheal activity and therapeutic response was endorsed to the suppression of normal and wet stools in Spraug Dawley rats. Through the series of fractionations, compound-A was obtained from methanolic extract and named 3-(4-amino 1,3,8-tri-OH 5,6-di-CH3 7-propyl 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl) propanoic3-(4-NH3 7-butyl 1,3,8-tri-OH 5,6-di-CH3 1,2,3,4,4a,5,8,8a-octahydronaphthalen 2-yl)propanoic anhydride. Compound-B was entitled 5-(3-hydroxy-1,4-di-CH3-1,2,3,4,4a,5,8,8a-octahydronaphthalen-2-yl)pent-3-enoic acid was acquired from the chloroform extract. The structure elucidations of both compounds were interpreted through spectroscopic data, including EI-MS, FTIR, 1HNMR and 13C-NMR. The significant antidiarrheal activities were determined with crude extracts and isolated compounds. In inference, present study revealed that substantial antidiarrheal feature of guava is confined to the identified compounds.


Asunto(s)
Antidiarreicos/farmacología , Diarrea/prevención & control , Extractos Vegetales/farmacología , Psidium , Animales , Antidiarreicos/aislamiento & purificación , Aceite de Ricino , Fraccionamiento Químico , Diarrea/inducido químicamente , Modelos Animales de Enfermedad , Estructura Molecular , Pakistán , Extractos Vegetales/aislamiento & purificación , Hojas de la Planta , Psidium/química , Ratas Sprague-Dawley , Relación Estructura-Actividad
16.
Pak J Pharm Sci ; 32(6(Supplementary)): 2771-2777, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32024613

RESUMEN

Medicinal plants are proven to reveal vast promising potential providing novel drug candidates to combat health-related problems. The aim of current study is to discover new drug compounds with anti-anticancer, antioxidant, antibacterial and antifungal potential, to serve the purpose Saussurea heteromalla (Family: Asteraceae) indigenous to Pakistan was screened for the in vitro cytotoxicity against HeLa cells (Human cervical cancer cell line) compared to the NIH / 3T3 cells (mouse normal fibroblast cells) by performing the MTT colorimetric assay and antifungal, antibacterial and antioxidant potential by adopting standard protocols. S. heteromalla crude methanolic extract (CME) demonstrated strong cytotoxic potential against HeLa cells at 200µg/mL; (77.28 ±1.53% kill; IC50: 62.13µg/mL) compared to standard doxorubicin (95.90% kill; IC50: 0.2µg/mL). Inhibitory Zone of the extract at concentrations (30, 60, 90µg/mL) against Bacillus subtilis, Serratia marecescens, Staphylococcus aureus, Micrococcus luteus, Pseudomonas aeruginosa, Strptotropomonas maltophilia, Escherichia coli, Salmonella typhi, and Saccharomyces cerevisiae, Candida albicans, Candida glabrata was measured. Manifestation of intensified results against Gram-negative Serratia marecescens qualifies the S. heteromalla extract as a considerable source of narrow spectrum antibiotic. However, antifungal activity against C. albicans was found to be logical. Antioxidant potential was determined through DPPH assay which declared no notable antioxidant effects. To the best of our knowledge this is first research and report on above mentioned biological studies of S. heteromalla.


Asunto(s)
Antibacterianos/farmacología , Antifúngicos/farmacología , Antioxidantes/fisiología , Extractos Vegetales/farmacología , Animales , Bacterias/efectos de los fármacos , Candida albicans/efectos de los fármacos , Línea Celular , Línea Celular Tumoral , Células HeLa , Humanos , Ratones , Pruebas de Sensibilidad Microbiana/métodos , Células 3T3 NIH , Pakistán , Plantas Medicinales/química
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