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The present study was undertaken on the chemical constituents of ethanol extract of aerial parts of Nyctanthes arbor-tristis Linn., and their determination of growth inhibitory activity against glioblastoma multiforme cell line (U87) and urease inhibitory activity. Six constituents were isolated including two new arbortristoside F tetraacetate (1) and arbortristoside G heptaacetate (2) and four known arborside A tetraacetate (3), arborside C pentaacetate (4), 6,7-di-O-acetyl-6ß-hydroxyloganin hexaacetate (5) and nyctanthoside heptaacetate (6) iridoid glycoside acetates. Their structures were elucidated using spectroscopic methods, including 1D and 2D NMR and mass analyses. Compounds 3 and 6 showed significant growth inhibition of U87 cell line (76.41 and 87.62% inhibition) respectively while 2, 4 and 5 showed moderate inhibition. 3 and 6 showed notable urease inhibition (IC50 = 17.2 ± 0.4 and 17.2 ± 0.7 µM) respectively, and IC50 of 2, 4 and 5 were 23.8 - 56.3 µM. Compound 1 was inactive.
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ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbor-tristis Linn. has been used by Ayruvedic physicians for the cure of different diseases including ulcers, gastric and inflammatory diseases. AIM OF THE STUDY: To isolate and identify compounds from this source and investigate their therapeutic potential for the treatment of gastric ulcer and related disorders. MATERIAL AND METHODS: The ethanol extract of fresh aerial parts of N. arbor-tristis was used in the present studies which was subjected to a bio-assay guided fractionation followed by chromatographic separations. The structures of pure compounds were elucidated using various spectroscopic techniques. The inhibition of urease enzyme was evaluated by weatherburn indophenol method. Molecular docking studies were determined by using Molecular Operating Environment (MOE) version 2020.0901 version. The intracellular ROS production from phagocytes was determined by chemiluminescence assay and NO generation was detected by Griess method. The proinflammatory cytokine TNF-α was quantified by ELISA. Cytotoxic activity was assessed by MTT assay. RESULTS: One previously undescribed iridoid glycoside arborside F (1) and four known iridoid glycosides arborside A (2), arborside C (3), loganin (4) and 7-O-trans-cinnamoyl-6ß-hydroxyloganin (5) were isolated and characterized in the present studies and their urease inhibitory activity was determined. Among these, 2 and 5 showed strong urease inhibition (IC50 = 12.1 ± 1.74 and 14.1 ± 0.59 µM respectively) (standard acetohydroxamic acid IC50 = 20.3 ± 0.42 µM), whereas rest of compounds showed moderate to low inhibition. Kinetic studies revealed that compounds 2 and 5 possess competitive type of inhibition. Molecular docking showed polar and non-polar interactions of compounds 2 and 5 with urease enzyme residues. Compounds 2 and 3 showed inhibition of ROS from whole blood (IC50 = 1.6 ± 0.3 and 2.5 ± 0.09 µg/mL respectively) and PMNs (IC50 = 1.5 ± 0.03 and 1.4 ± 0.0 µg/mL respectively). Compound 2 significantly inhibited nitric oxide and proinflammatory cytokine TNF-α (IC50 = 18.2 ± 3.0 and 73.8 ± 6.6 µg/mL respectively). Compounds 1, 4 and 5 were inactive on ROS. All isolated compounds were non-toxic on normal mouse fibroblasts (NIH-3T3) cells. CONCLUSIONS: The ethno pharmacological repute of N. arbor-tristis in treating gastric and anti-inflammatory ailments is supported by present studies which resulted in isolation of a potent urease inhibitory and anti-inflammatory agent arborside A (2) a potential anti-ulcer and anti-inflammatory drug lead.
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Extractos Vegetales , Ureasa , Ratones , Animales , Extractos Vegetales/uso terapéutico , Glicósidos Iridoides/farmacología , Cinética , Simulación del Acoplamiento Molecular , Especies Reactivas de Oxígeno , Factor de Necrosis Tumoral alfa , Antiinflamatorios/farmacologíaRESUMEN
Macromolecules i.e., carbohydrate derivatives are crucial to biochemical and medical research. Herein, we designed and synthesized eight methyl α-D-glucopyranoside (MGP) derivatives (2-8) in good yields following the regioselective direct acylation method. The structural configurations of the synthesized MGP derivatives were analyzed and verified using multiple physicochemical and spectroscopic techniques. Antimicrobial experiments revealed that almost all derivatives demonstrated noticeable antifungal and antibacterial efficacy. The synthesized derivatives showed minimum inhibitory concentration (MIC) values ranging from 0.75 µg/mL to 1.50 µg/mL and minimum bactericidal concentrations (MBCs) ranging from 8.00 µg/mL to 16.00 µg/mL. Compound 6 inhibited Ehrlich ascites carcinoma (EAC) cell proliferation by 10.36% with an IC50 of 2602.23 µg/mL in the MTT colorimetric assay. The obtained results were further rationalized by docking analysis of the synthesized derivatives against 4URO and 4XE3 receptors to explore the binding affinities and nonbonding interactions of MGP derivatives with target proteins. Compound 6 demonstrated the potential to bind with the target with the highest binding energy. In a stimulating environment, a molecular dynamics study showed that MGP derivatives have a stable conformation and binding pattern. The MGP derivatives were examined using POM (Petra/Osiris/Molinspiration) bioinformatics, and as a result, these derivatives showed good toxicity, bioavailability, and pharmacokinetics. Various antifungal/antiviral pharmacophore (Oδ-, O'δ-) sites were identified by using POM investigations, and compound 6 was further tested against other pathogenic fungi and viruses, such as Micron and Delta mutants of SARS-CoV-2.
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Nucleoside analogs are an important, well-established class of clinically useful medicinal agents that exhibit potent antimicrobial activity. Thus, we designed to explore the synthesis and spectral characterization of 5'-O-(myristoyl)thymidine esters (2-6) for in vitro antimicrobial, molecular docking, molecular dynamics, SAR, and POM analyses. An unimolar myristoylation of thymidine under controlled conditions furnished the 5'-O-(myristoyl)thymidine and it was further converted into four 3'-O-(acyl)-5'-O-(myristoyl)thymidine analogs. The chemical structures of the synthesized analogs were ascertained by analyzing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial tests along with PASS, prediction indicated expectant antibacterial functionality of these thymidine esters compared to the antifungal activities. In support of this observation, their molecular docking studies have been performed against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) and significant binding affinities and non-bonding interactions were observed. The stability of the protein-ligand complexes was monitored by a 100 ns MD simulation and found the stable conformation and binding mode in a stimulating environment of thymidine esters. Pharmacokinetic predictions were studied to assess their ADMET properties and showed promising results in silico. SAR investigation indicated that acyl chains, lauroyl (C-12) and myristoyl (C-14), combined with deoxyribose, were most effective against the tested bacterial and fungal pathogens. The POM analyses provide the structural features responsible for their combined antibacterial/antifungal activity and provide guidelines for further modifications, with the aim of improving each activity and selectivity of designed drugs targeting potentially drug-resistant microorganisms. It also opens avenues for the development of newer antimicrobial agents targeting bacterial and fungal pathogens.
A novel series of 5´-O-(myristoyl)thymidine derivatives were synthesized and characterized by FTIR, 1H-NMR, 2D-NMR, 13C-NMR, mass and physicochemical studies.In vitro antimicrobial susceptibility revealed that alkyl chain and aromatic substituents can improve the antimicrobial efficacy of the thymidine structure which was also supported by PASS enumeration.Molecular docking study against lanosterol 14α-demethylase (CYP51A1) and Aspergillus flavus (1R51) exhibited a promising binding score and interaction in the catalytic active site.A 100ns MD simulation revealed the stable conformation and binding pattern in a stimulating environment of thymidine derivatives.ADMET analysis revealed that most of the compounds are non-toxic and most of them have an inhibitory property to the CYP1A2 and CYP3A4In silico and POM analyses provide substantial ideas about the structural features responsible for their combined antibacterial/antifungal agents and provide guidelines for further modifications.
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Antiinfecciosos , Antifúngicos , Antifúngicos/química , Simulación del Acoplamiento Molecular , Antibacterianos/química , Bacterias , Ésteres/química , Timidina/farmacología , Estructura Molecular , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
Because of their superior antibacterial and pharmacokinetic capabilities, many nucleoside-based esters show potential against microorganisms, and may be used as pharmacological agents to address multidrug-resistant pathogenic problems. In this study, several aliphatic and aromatic groups were inserted to synthesize various 5'-O-decanoyluridine (2-5) and 5'-O-lauroyluridine derivatives (6-7) for antimicrobial, in silico computational, pharmacokinetic and POM (Petra/Osiris/Molinspiration). The chemical structures of the synthesized uridine derivatives were confirmed by physicochemical, elemental, and spectroscopic analyses. In vitro antimicrobial screening against five bacteria and two fungi, as well as the prediction of substance activity spectra (PASS), revealed that these uridine derivatives have promising antifungal properties when compared to the antibacterial activities. Density functional theory (DFT) was used to calculate the thermodynamic and physicochemical properties. Molecular docking was conducted against lanosterol 14a-demethylase CYP51A1 (3JUV) and Aspergillus flavus (1R4U) and revealed binding affinities and non-covalent interactions with the target. Then, a 150 ns molecular dynamic simulation was performed to confirm the behavior of the complex structure formed by microbial protein under in silico physiological conditions to examine its stability over time, which revealed a stable conformation and binding pattern in a stimulating environment of uridine derivatives. The acyl chain {CH3(CH2)9CO-} and {CH3(CH2)10CO-} in conjunction with sugar, was determined to have the most potent activity against bacterial and fungal pathogens in a structure-activity relationships (SAR) investigation. POM analyses were conducted with the presence of an antifungal (O δ- -- O' δ-) pharmacophore site. Overall, the present study might be useful for the development of uridine-based novel multidrug-resistant antimicrobial.
Novel uridine derivatives were designed and synthesized. The chemical structures and purity of these new uridine derivatives were confirmed by usual spectroscopic techniques.In vitro antimicrobial activity and SAR study was investigated. The incorporation of various aliphatic and aromatic groups in uridine structure significantly increased their biological activity.PASS prediction analysis indicated that the compounds were less potent as anti-carcinogenic agents (0.31 < Pa < 0.52) than as antimicrobial agents.Molecular docking analysis showed that the novel uridine derivatives 2, 5 and 6 may possess excellent effectiveness for lanosterol 14a-demethylase CYP51A1 (3JUV) and Aspergillus flavus (1R4U).The stability of the docked complex was confirmed by performing molecular dynamics along with an estimation of MMPB/GBSA binding free energy which ensured that complex of derivatives 2, 5 and 6 were reported in improved dynamics stability as revealed by their uniform RMSD and RMSF profiles.In silico ADMET calculations predicted improved pharmacokinetic properties of all uridine derivatives.The POM analysis showed the presence of an antifungal (O δ− --- O' δ−) pharmacophore site.
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Antiinfecciosos , Simulación de Dinámica Molecular , Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Bacterias , Lanosterol , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Nucleósidos/farmacología , Relación Estructura-Actividad , Azúcares , Uridina/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Nyctanthes arbor-tristis Linn. is native to Indo-Pak sub-continent and has high medicinal values in Ayureda. This plant has been used traditionally for the treatment of sciatica, rheumatism, chronic fever, diabetes, snakebite, dysentery, cachexia and cancer. Studies have shown many pharmacological properties such as anti-cancer efficacy against Dalton's ascetic lymphoma, cytotoxicity against T-cell leukemia, anti-inflammatory, anti-diabetic and anti-oxidant effects. AIM OF THE STUDY: Aim of the study was to explore the anti-inflammatory and anti-proliferative potential of N. arbor-tristis. MATERIAL AND METHODS: Ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis was used in the present study. A new compound nyctanthesin A was isolated following a bioactivity-guided fractionation and chromatographic separations. Its chemical structure was elucidated through spectral studies including 1D, 2D-NMR experiments and HREIMS. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) generation from phagocytes were detected by chemiluminescence technique and Griess method, respectively. TNF-α and TGF-ß production was quantified by ELISA. Anti-lymphoma and cytotoxic activities were assessed by alamar blue and MTT assays, respectively. The transcription and protein expression level of Bcl-2, COX-2, p38 MAPK, PDL-1, NF-κB, c-Myc and PNF-κB was performed by qRT-PCR and protein blot assays, respectively. RESULTS: Petroleum ether insoluble fraction of the ethanol extract of fresh and uncrushed aerial parts of N. arbor-tristis revealed anti-inflammatory potential by inhibiting ROS. A previously undescribed compound nyctanthesin A was isolated from this fraction and characterized by UV, IR, NMR and HREIMS. It showed significant anti-inflammatory property by inhibiting ROS, NO and TNF-α production. The strong anti-proliferative effects on B- cell lymphoma cells, DOHH2 and Raji, revealed its anti-lymphoma potential along with non-toxic profile against BJ and NIH-3T3 fibroblast cells of normal origin. The qRT-PCR results showed marked inhibition of Bcl-2, COX-2, p38 MAPK, PDL-1, c-Myc, NF-κB, and PNF-κB at transcription level in DOHH2 cells with comparatively lesser but significant effects in Raji cells, where the expression of Bcl-2 gene was not affected. The protein expression of PNF-κB in DOHH2 cells was inhibited by 66% (P < 0.05) and COX-2 in both cell lines was inhibited by 50% (P < 0.05) at 60 µg/mL. A moderate non-significant inhibition of TGF-ß (â¼20%) was observed in both cell lines at 100 µg/mL CONCLUSIONS: Scientific evidences reported here validate the anti-inflammatory and anti-cancer potential of the plant.
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Linfoma no Hodgkin , Oleaceae , Antiinflamatorios/farmacología , Ciclooxigenasa 2/genética , Etanol , Humanos , Lipopolisacáridos , Linfoma no Hodgkin/tratamiento farmacológico , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Oleaceae/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2 , Especies Reactivas de Oxígeno , Factor de Crecimiento Transformador beta , Factor de Necrosis Tumoral alfa , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
BACKGROUND: One of the best methods to treat Alzheimer disease (AD) is through the effective use of cholinesterase inhibitors as vital drugs due to the identification of acetylcholine deficit in the AD patients. OBJECTIVE: The present study aims the investigation of spiro heterocyclic compounds as potential AD agents supported by their metal chelation capacity, POM analyses and DFT studies, respectively. METHODS: The cholinesterase inhibition and metal chelation ability were performed on ELISA microtiter assay. Whereas, the B3LYP method with 6-31+G(d,p) basis set was implemented to study HOMOLUMO energy calculations. The pharmacokinetic properties of the synthesized molecules were studied through Petra, Osiris and Molinspiration (POM). RESULTS: The six spiro (1-6) skeletons were tested for their inhibitory potential and metal-chelation capacity. Our findings revealed that the tested spiro skeletons exerted none or lower than 50% inhibition against both cholinesterases, while compound 4 proved to be the most active molecule with 57.21±0.89% of inhibition toward BChE. The spiro molecule 3 exhibited the highest metal-chelation capacity (9.12±5.26%). Molecular docking model for the most active molecule exhibited promising bindings with AChE and BChE's active site pertained to hydrophobic hydrogen bonds and positive ionizable interactions. The POM analyses gave the information about the flexibility at the site of coordination of spiro compounds (1-6). CONCLUSION: The screening of spirocompounds (1-6) against cholinesterases revealed that some of them show considerable potential to inhibit AChE and BChE. Herein, we propose that the spiro molecules after further derivatization could serve interesting AD inhibitor drugs.
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Enfermedad de Alzheimer/tratamiento farmacológico , Quelantes/química , Quelantes/farmacología , Compuestos Heterocíclicos/química , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Conformación Molecular , Simulación del Acoplamiento Molecular , Compuestos de Espiro/uso terapéutico , Relación Estructura-ActividadRESUMEN
BACKGROUND: The quinoline ring system is one of the most commonly encountered heterocycles in medicinal chemistry, due to the pharmaceutical and medicinal uses of derivatives containing this ring. These quinoline-based compounds have remarkable biological activity, as they are employed as antimalarial, antibacterial, antifungal, and antitumor agents. The quinoline nucleus can be synthesized by various traditional methods such as the Skraup reaction, Friedlaender synthesis, Combes quinoline synthesis, Larock quinoline synthesis, among others. METHODS: The aim of the present work is to synthesize a number of new arylated quninolines having significant antinoceciptive effect through the Suzuki-Miyaura cross coupling reaction using 3- bromoquinoline as a starting material. RESULTS: A number of new quinoline derivatives have been synthesized. Structures of the newly synthesized compounds were confirmed by means of IR, NMR, and mass spectrometry, and by elemental analysis. In addition, the molecular structures of two representative derivatives were determined with the aid of X-ray crystallography. Additionally, the antinociceptive activity of the prepared compounds was evaluated in vivo; results revealed that most of the tested compounds exhibited a dosedependent antinociceptive effect. CONCLUSION: Prepared compounds were found to exhibit significant antinociceptive activities and could be used as potential analgesic agents. Further work, however, may be required to establish the safety and efficacy of these compounds.
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Analgésicos/uso terapéutico , Dolor/tratamiento farmacológico , Quinolinas/uso terapéutico , Ácido Acético , Analgésicos/síntesis química , Analgésicos/química , Animales , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Modelos Moleculares , Estructura Molecular , Dolor/inducido químicamente , Quinolinas/síntesis química , Quinolinas/química , Relación Estructura-ActividadRESUMEN
Mass spectrometry has been widely used, particularly in pharmacokinetic investigations and for therapeutic drug monitoring purposes. Like any other analytical method some difficulties exist in employing mass spectrometry, mainly when it is used to test biological samples, such as to detect drug candidates in mammalian serum, which is rich in proteins, lipids and other contents that may interfere with the investigational drug. The complexity of the serum proteome presents challenges for efficient sample preparation and adequate sensitivity for mass spectrometry analysis of drugs. Enrichment procedures prior to the drug analysis are often needed and as a result, the study of serum or plasma components usually demands either methods of purification or depletion of one or more. Selection of the best combination of sample introduction method is a crucial determinant of the sensitivity and accuracy of mass spectrometry. The aim of this study was to determine the highest serum protein precipitation activity of five commonly used sample preparation methods and test their suitability for mass spectrometry. We spiked three small molecules into rabbit serum and applied different protein precipitation methods to determine their precipitation activity and applicability as a mass spectrometry introductory tool.
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The novel N-1 and C5 alkyl substituted derivatives of pyrimidine were synthesized by using tetrabutyl ammonium bromide (TBAB) as phase transfer catalyst at 20-25 °C with excellent productivity (85-95%). The new compounds were evaluated for their antibacterial activities by screening them against Gram-positive and Gram-negative bacterial strain: Staphylococcus aureus ATCC 6538P, Salmonella abony NCTC 6017: Escherichia coli ATCC 8739, Staphylococcus epidermidis ATCC 12228. Among all compounds evaluated the molecule 2c and (2g-j) exhibit the most pronounced antibacterial activity against E. coli, S. aureus and S. abony with MICs value 25 µg/mL.
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Antibacterianos/síntesis química , Antibacterianos/farmacología , Pirimidinas/química , Pirimidinas/farmacología , Antibacterianos/química , Cristalografía por Rayos X , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Salmonella/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
A series of new 2-aminobenzamide derivatives (1-10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution.
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Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , ortoaminobenzoatos/síntesis química , ortoaminobenzoatos/farmacología , Antiinfecciosos/química , Aspergillus fumigatus/efectos de los fármacos , Aspergillus fumigatus/crecimiento & desarrollo , Bacillus subtilis/efectos de los fármacos , Bacillus subtilis/crecimiento & desarrollo , Candida albicans/efectos de los fármacos , Candida albicans/crecimiento & desarrollo , Cristalización , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Modelos Químicos , Estructura Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/crecimiento & desarrollo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Relación Estructura-Actividad , ortoaminobenzoatos/químicaRESUMEN
Three complexes of the general formula trans/cis-[Ru((II))(dppme)(N-N)Cl2] {dppme is H2C=C(CH2PPh2)2 and N-N is 1,2-diaminocyclohexane (trans/cis-(1)) and 1-methyl-1,2-diaminopropane (trans-(2)} were obtained by reacting trans-[RuCl2(dppme)2] with an excess amount of corresponding diamine in CH2Cl2 as a solvent. The complexes were characterized by an elemental analysis, IR, (1)H, (13)C and (31)P{1H} NMR, FAB-MS and UV-visible. The trans-(1) (kinetic product) readily isomerizes to the cis-(1) (thermodynamic product) and this process was followed by using (31)P{(1)H} NMR, cyclic voltammetry and UV-vis spectroscopy. The electrochemical studies on complex (1) reveal that the Ru(III)/Ru(II) couples are sensitive to the isomer (trans/cis) formed. The cis-(1) was confirmed by X-ray structure and (31)P{(1)H} NMR. Transfer-hydrogenation reactions for reduction of trans-4-phenyl-3-butene-2-one were conducted using complexes trans/cis-(1) and trans-(2). The electronic spectra of cis/trans-(1) in dichloromethane were calculated with the use of time-dependent DFT methods.
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Complejos de Coordinación/química , Complejos de Coordinación/metabolismo , Diaminas/química , Cetonas/química , Compuestos de Rutenio/química , Compuestos de Rutenio/metabolismo , Catálisis , Cristalografía por Rayos X , Electroquímica , Hidrogenación , Espectroscopía de Resonancia Magnética , Modelos Moleculares , Estructura Molecular , Espectrofotometría Ultravioleta , Estereoisomerismo , TermodinámicaRESUMEN
In the present study, we have carried out extensive General Unrestricted Structure-Activity Relationships, conventional 3D-Quantitative Structure-Activity Relationships, and CoMFA analyses of synthetic prodiginines displaying moderate to high activities against Plasmodium Falciperum. 2D and 3D descriptors, various statistical parameters viz. R(2), R(2)(adj), standard error, Y-randomization, etc., were checked to build fruitful 3D-Quantitative Structure-Activity Relationships model. The best five parametric 3D-Quantitative Structure-Activity Relationships model is with R(2) = 0.924 and R(2)(pred) = 0.901. CoMFA was performed to check the electrostatic and steric regions, which affect the activity. The CoMFA model is graphically inferred using contour plots, which provide insight into the structural requirements for increasing the activity of a compound. The General Unrestricted Structure-Activity Relationships model, with R(2) = 0.940 and Q(2) = 0.912, suggests that the presence of F on aromatic ring is good for activity. The analyses reveal that lipophilicity plays a crucial role in deciding the activity for these molecules.
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Antimaláricos/química , Prodigiosina/análogos & derivados , Relación Estructura-Actividad Cuantitativa , Antimaláricos/síntesis química , Modelos Moleculares , Prodigiosina/síntesis química , Prodigiosina/química , Electricidad EstáticaRESUMEN
A new series of oxovanadium(IV) complexes have been designed and synthesized with a new class of triazole Schiff bases derived from the reaction of 3,5-diamino-1,2,4-triazole with 2-hydroxy-1-naphthaldehyde, pyrrole-2-carboxaldehyde, pyridine-2-carboxaldehyde and acetyl pyridine-2-carboxaldehyde, respectively. Physical (magnetic susceptibility, molar conductance), spectral (IR, (1)H NMR, (13)C NMR, mass and electronic) and analytical data have established the structures of these synthesized Schiff bases and their oxovanadium(IV) complexes. The Schiff bases, predominantly act as bidentate and coordinate with the vanadium(IV) metal to give a stoichiometric ratio of 1:2 [M:L], forming a general formulae, [M(L-H)(2)] and [M(L)(2)]SO(4) where L = (L(1))-(L(4)) and M = VO(IV) of these complexes in a square-pyramidal geometry. In order to evaluate the biological activity of Schiff bases and to assess the role of vanadium(IV) metal on biological activity, the triazole Schiff bases and their oxovanadium(IV) complexes have been studied for in vitro antibacterial activity against four Gram-negative (Escherichia coli, Shigella flexenari, Pseudomonas aeruginosa, Salmonella typhi) and two Gram-positive (Staphylococcus aureus, Bacillus subtilis) bacterial strains, in vitro antifungal activity against Trichophyton longifucus, Candida albican, Aspergillus flavus, Microscopum canis, Fusarium solani and Candida glaberata. The simple Schiff bases showed weaker to significant activity against one or more bacterial and fungal strains. In most of the cases higher activity was exhibited upon coordination with vanadium(IV) metal. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina.