Synthesis, Molecular Docking and DFT Studies of Biologically Active
N-((3-(4-Nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)aniline Derivatives

Some biologically active pyrazole clubbed imino molecules have been designed and synthesized from 1-phenyl-3-nitro phenyl-1H- pyrazol-4-carboxaldehyde and substituted aromatic amines via acid catalyzed condensation reaction. All the synthesized molecules were characterized by IR, 1H NMR, 13C NMR and mass spectral techniques. The in vitro antibactericidal property of the synthesized compounds was screened and compared with the results of theoretical molecular docking. Optimization of molecular geometry, DNA binding interaction and FMO analysis were also investigated by computational studies using Gaussian 16 package at B3LYP/6-31G(d,p) level. All the synthesized compounds exhibited moderate to good biological activities both experimentally and theoretically.

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Synthesis, DFT Calculations, DNA Binding and Molecular Docking Studies on Biologically Active N-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)naphthyl Derivatives

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2021.ajomc-p351 ◽

2021 ◽

Vol 6 (4) ◽

pp. 292-301

Author(s):

P.V. Sandhya ◽

K.S. Femina ◽

A.V. Pradeep

Keyword(s):

Molecular Docking ◽

Dna Binding ◽

Biological Activities ◽

Condensation Reaction ◽

Geometry Optimization ◽

Docking Study ◽

Biologically Active ◽

Molecular Docking Study ◽

Binding Interaction

The biologically active pyrazole clubbed imino naphthyl derivatives have been designed and synthesized from 1-phenyl-3-methoxy phenyl-1H-pyrazol-4-carboxaldehyde and substituted naphthyl amines via acid catalyzed condensation reaction. All the synthesized compounds were well characterized by different spectroscopic and mass spectral techniques. The in vitro antibacterial, antifungal and antituberculosis studies were carried out. The molecular docking study was also done with the software Arguslab 4.0.1. The studied compounds showed moderate to good biological activities both experimentally and theoretically. Geometry optimization, DNA binding interaction and FMO analysis were also investigated with the help of Gaussian 16 package at B3LYP/6-31G(d,p) level.

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Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

Letters in Drug Design & Discovery ◽

10.2174/1573413715666181212150955 ◽

2019 ◽

Vol 16 (6) ◽

pp. 696-710

Author(s):

Mahmoud Balbaa ◽

Doaa Awad ◽

Ahmad Abd Elaal ◽

Shimaa Mahsoub ◽

Mayssaa Moharram ◽

...

Keyword(s):

Oxidative Stress ◽

Molecular Docking ◽

Active Sites ◽

Biological Activities ◽

Imidazole Ring ◽

Quantitative Structure Activity Relationship ◽

Binding Interaction ◽

Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

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Design and Synthesis of Novel 1,3-Thiazole and 2-Hydrazinyl-1,3-Thiazole Derivatives as Anti-Candida Agents: In Vitro Antifungal Screening, Molecular Docking Study, and Spectroscopic Investigation of their Binding Interaction with Bovine Serum Albumin

Molecules ◽

10.3390/molecules24193435 ◽

2019 ◽

Vol 24 (19) ◽

pp. 3435 ◽

Cited By ~ 6

Author(s):

Andreea-Iulia Pricopie ◽

Ioana Ionuț ◽

Gabriel Marc ◽

Anca-Maria Arseniu ◽

Laurian Vlase ◽

...

Keyword(s):

Molecular Docking ◽

Bovine Serum Albumin ◽

Serum Albumin ◽

Bovine Serum ◽

Rapid Development ◽

Biologically Active ◽

Thiazole Derivatives ◽

Binding Interaction ◽

Reference Drug

In the context of there being a limited number of clinically approved drugs for the treatment of Candida sp.-based infections, along with the rapid development of resistance to the existing antifungals, two novel series of 4-phenyl-1,3-thiazole and 2-hydrazinyl-4-phenyl-1,3-thiazole derivatives were synthesized and tested in vitro for their anti-Candida potential. Two compounds (7a and 7e) showed promising inhibitory activity against the pathogenic C. albicans strain, exhibiting substantially lower MIC values (7.81 μg/mL and 3.9 μg/mL, respectively) as compared with the reference drug fluconazole (15.62 μg/mL). Their anti-Candida activity is also supported by molecular docking studies, using the fungal lanosterol C14α-demethylase as the target enzyme. The interaction of the most biologically active synthesized compound 7e with bovine serum albumin was investigated through fluorescence spectroscopy, and the obtained data suggested that this molecule might efficiently bind carrier proteins in vivo in order to reach the target site.

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Cardenolides and pentacyclic triterpenes isolated from Acokanthera oblongifolia leaves: their biological activities with molecular docking study

Zeitschrift für Naturforschung C ◽

10.1515/znc-2020-0198 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Howaida I. Abd-Alla ◽

Maha M. Soltan ◽

Amal Z. Hassan ◽

Hanan A. A. Taie ◽

Heba M. Abo-Salem ◽

...

Keyword(s):

Molecular Docking ◽

Topoisomerase I ◽

Biological Activities ◽

Molecular Docking Study ◽

2D Nmr Spectroscopy ◽

Binding Interaction ◽

Pentacyclic Triterpenes ◽

Chemical Structures ◽

H5n1 Influenza

Abstract Pentacyclic triterpenes and cardenolides were isolated from Acokanthera oblongifolia leaves. Their chemical structures were determined based on comprehensive 1D and 2D NMR spectroscopy. Their MIC was determined against 12 microorganisms. Their exerted cytotoxicity on the immortalized normal cells, hTERT-RPE1 was assessed by the sulforhodamine-B assay. The viral inhibitory effects of compounds against Newcastle disease virus (NDV) and H5N1 influenza virus IV were evaluated. Four in vitro antioxidant assays were performed in comparison with BHT and trolox and a weak activity was exhibited. Acovenoside A was with potent against H5N1-IV and NDV with IC50 ≤ 3.2 and ≤ 2.1 μg/ml and SI values of 93.75 and 95.23%, respectively, in comparison to ribavirin. Its CC50 record on Vero cells was > 400 and 200 μg/ml, respectively. Acobioside A was the most active compound against a broad range of microbes while Pseudomonas aeruginosa was the most sensitive. Its MIC (0.07 μg/ml) was 1/100-fold of the recorded CC50 (7.1 μg/ml/72 h) against hTERT-RPE1. The molecular docking of compounds on human DNA topoisomerase I (Top1-DNA) and IV glycoprotein hemagglutinin were studied using MOE program. This study has introduced the cardenolides rather than triterpenoids with the best docking score and binding interaction with the active site of the studied proteins.

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Metabolomics of Healthy Berry Fruits

Current Medicinal Chemistry ◽

10.2174/0929867323666161206100006 ◽

2019 ◽

Vol 25 (37) ◽

pp. 4888-4902 ◽

Cited By ~ 3

Author(s):

Gilda D'Urso ◽

Sonia Piacente ◽

Cosimo Pizza ◽

Paola Montoro

Keyword(s):

Biological Activities ◽

Biologically Active ◽

In Vivo Studies ◽

Bioactive Metabolites ◽

Active Metabolites ◽

Positive Effects ◽

Cell Functions ◽

Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

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1'-methylspiro[indoline-3,4'-piperidine] Derivatives: Design, Synthesis, Molecular Docking and Anti-tumor Activity Studies

Letters in Drug Design & Discovery ◽

10.2174/1570180817999201117150714 ◽

2020 ◽

Vol 17 ◽

Author(s):

Junjian Li ◽

Lianbao Ye ◽

Yuanyuan Wang ◽

Ying Liu ◽

Xiaobao Jin ◽

...

Keyword(s):

Molecular Docking ◽

Cell Lines ◽

Active Sites ◽

Biological Activities ◽

Significant Inhibition ◽

Alkaline Condition ◽

Discovery Studio ◽

Hela Cell Lines ◽

Antiproliferative Activities

Background: Spirocyclic indoline compounds widely exist in numerous natural products with good biological activities and some drug molecules in many aspects. In recent years, it has attracted extensive attention as potent anti-tumor agents in the fields of pharmacology and chemistry. Objective: In this study, we focused on designing and synthesizing a set of novel 1'-H-spiro[indole-3,4'-piperidine] derivatives, which were evaluated by preliminary bioactivity experiment in vitro and molecular docking. Method: The key intermediate 1'-methylspiro[indoline-3,4'-piperidine] (B4) reacted with benzenesulfonyl chloride with different substituents under alkaline condition to obtain its sulfonyl derivatives (B5-B10). We evaluated their antiproliferative activities against A549, BEL-7402 and HeLa cells by MTT assay. We performed the CDOCKER module in Discovery Studio 2.5.5 software for molecular modeling of compound B5, and investigated the binding of compound B5 with the target proteins from PDB database. Results: The results indicated that compounds B4-B10 exhibited good antiproliferative activities against the above three types of cells, in which compound B5 with chloride atom as electron-withdrawing substituent on a phenyl ring showed the highest potency against BEL-7402 cells (IC50=30.03±0.43 μg/mL). By binging of the prominent bioactive compound B5 to CDK, c-Met, EGFR protein crystals, The binding energy of B5 with these three types receptors are -44.3583 kcal/mol, - 38.3292 kcal/mol, -33.3653 kcal/mol respectively. Conclusion: Six 1'-methylspiro[indoline-3,4'-piperidine] derivatives were synthesized and evaluated against BEL-7402, A- 549, HeLa cell lines. Compound B5 showed significant inhibition on BEL-7402 cell lines. Molecular docking revealed that B5 showed good affinity by the good fitting between B5 and these three targets with amino acid residues in active sites which encourage us to conduct further evaluation such as the kinase experiment.

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Chalcones: As potent α-amylase enzyme inhibitors; synthesis, in vitro, and in silico studies

Medicinal Chemistry ◽

10.2174/1573406416666200611103039 ◽

2020 ◽

Vol 16 ◽

Author(s):

Mahboob Ali ◽

Momin Khan ◽

Khair Zaman ◽

Abdul Wadood ◽

Maryam Iqbal ◽

...

Keyword(s):

In Silico ◽

Enzyme Inhibitors ◽

Biological Activities ◽

Condensation Reaction ◽

Type Ii Diabetes Mellitus ◽

Spectroscopic Techniques ◽

Chalcone Derivatives ◽

In Silico Studies ◽

Wide Range

: Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities. Objective: In the current study chalcone derivatives (1-17) were synthesized and evaluated their inhibitory potential against α-amylase enzyme. Method: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by ClaisenSchmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HREI-MS, 1H-, and 13C-NMR. Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC50 = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC50 = 1.34 ± 0.3 μM). Conclusion: Chalcone derivatives (1-17) were synthesized, characterized, and evaluated for their α-amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

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Preservation of immunological and biological activities of insulin by insulinase inhibitor in vitro

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y70-048 ◽

1970 ◽

Vol 48 (5) ◽

pp. 291-298

Author(s):

J. Pierluissi ◽

J. Campbell ◽

K. S. Rastogi ◽

G. R. Green ◽

V. Lazdins

Keyword(s):

Biological Effect ◽

Biological Activities ◽

Biologically Active ◽

Immunoreactive Insulin ◽

Maximal Velocity ◽

Appreciable Change ◽

Glycogen Accumulation ◽

Fractional Rate ◽

Diaphragm In Vitro

The relation of insulinase activity to the biological effect of insulin on isolated tissue was studied. Rat diaphragm in vitro caused the rapid disappearance of immunoreactive insulin (IRI) in physiological concentrations. IRI loss at time intervals was exponential. The fractional rate of loss of IRI was therefore independent of IRI concentration and was also approximately constant per milligram of tissue, the value being 0.0216%/mg∙mm. The value of the Michaelis constant (Km), obtained from initial velocities at five initial concentrations of IRI, was 1.85 × 10−8M, and of the maximal velocity (Vmax) was 2.32 × 10−11 mole/g∙min, based on insulin dimer. The addition of an insulinase inhibitor (a partial hydrolysate of insulin) to hemidiaphragm in vitro reduced the fractional rate of IRI loss by 60%. The increase in Km, without appreciable change in Vmax, indicated that the inhibition was competitive. The IRI preserved by means of the inhibitor was biologically active, since it increased the glycogen accumulation and the incorporation of 14C-U-glucose into glycogen in a second, fresh hemidiaphragm. In single incubation of hemidiaphragm with insulin, the gain in glycogen was correlated with the amount of inhibitor. The biological effect of insulin on diaphragm in vitro was therefore limited by tissue insulinase activity, and insulinase inhibitor potentiated to some extent the action of insulin.

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Phytochemical Characterization and Evaluation of Biological Activities of Egyptian Carob Pods (Ceratonia siliqua L.) Aqueous Extract: In Vitro Study

Plants ◽

10.3390/plants10122626 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2626

Author(s):

Wael Sobhy Darwish ◽

Abada El Sayed Khadr ◽

Maher Abd El Naby Kamel ◽

Mabrouk A. Abd Eldaim ◽

Ibrahim El Tantawy El Sayed ◽

...

Keyword(s):

Aqueous Extract ◽

Biological Activities ◽

Radical Scavenging ◽

Antimicrobial Activities ◽

Biologically Active ◽

Phytochemical Analysis ◽

Type I ◽

Hypotonic Solution ◽

Ceratonia Siliqua

Ceratonia siliqua (Carob) is an evergreen Mediterranean tree, and carob pods are potentially nutritive and have medicinal value. The present study was carried out to estimate the possible biological activities of phytochemical-characterized carob pod aqueous extract (CPAE). The phytochemical contents of CPAE were determined by using colorimetric methods and HPLC. In addition, the free radical scavenging properties and anti-diabetic, anti-hemolytic, and antimicrobial activities were estimated by using standardized in vitro protocols. The phytochemical analysis revealed that CPAE was rich in polyphenols, flavonoids, and alkaloids, where it contained a significant amount of gallic acid, catechin, and protocatechuic acid. Furthermore, CPAE exhibited strong antioxidant activity where it prevented the formation of 2, 2-Diphenyl-1-picryl hydrazyl, hydroxyl, and nitric oxide free radicals. Additionally, it had a potent inhibitory effect against digestive enzymes (amylase, maltase, sucrase, and lactase). Moreover, CPAE exhibited anti-Staph aureus, anti-Escherichia coli, anti-Candida albicans, and anti-herpes simplex type I virus (HSV-I). Finally, CPAE protected the erythrocyte membrane from hypotonic solution-induced hemolysis. Altogether, CPAE could be regarded as an interesting source of biologically active antioxidant, anti-diabetic, and antimicrobial preparation for a potential application in pharmaceutical and food supplement fields.

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Chromatographic Analyses, In Vitro Biological Activities, and Cytotoxicity of Cannabis sativa L. Essential Oil: A Multidisciplinary Study

Molecules ◽

10.3390/molecules23123266 ◽

2018 ◽

Vol 23 (12) ◽

pp. 3266 ◽

Cited By ~ 38

Author(s):

Gokhan Zengin ◽

Luigi Menghini ◽

Antonella Di Sotto ◽

Romina Mancinelli ◽

Francesca Sisto ◽

...

Keyword(s):

Essential Oil ◽

Galleria Mellonella ◽

Cannabis Sativa ◽

Biological Activities ◽

Methodological Approach ◽

Volatile Component ◽

Biologically Active ◽

Antioxidant Compounds

Due to renewed interest in the cultivation and production of Italian Cannabis sativa L., we proposed a multi-methodological approach to explore chemically and biologically both the essential oil and the aromatic water of this plant. We reported the chemical composition in terms of cannabinoid content, volatile component, phenolic and flavonoid pattern, and color characteristics. Then, we demonstrated the ethnopharmacological relevance of this plant cultivated in Italy as a source of antioxidant compounds toward a large panel of enzymes (pancreatic lipase, α-amylase, α-glucosidase, and cholinesterases) and selected clinically relevant, multidrug-sensible, and multidrug-resistant microbial strains (Staphylococcus aureus, Helicobacter pylori, Candida, and Malassezia spp.), evaluating the cytotoxic effects against normal and malignant cell lines. Preliminary in vivo cytotoxicity was also performed on Galleria mellonella larvae. The results corroborate the use of this natural product as a rich source of important biologically active molecules with particular emphasis on the role exerted by naringenin, one of the most important secondary metabolites.

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