scholarly journals Novel Pyrimidine-Triazole Schiff Bases: Synthesis, Antifungal Activities, DFT and Molecular Docking

2020 ◽  
Vol 72 (4) ◽  
pp. 65-74
Author(s):  
Mou-Cui Li ◽  
Ying-Hui Ren ◽  
Yu-Ying Han ◽  
Yang-Ming Dong ◽  
Shao-Jie Wu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Broad Spectrum ◽  
Energy Gap ◽  
Stable Complex ◽  
Spectroscopic Techniques ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
Antifungal Activities

Seven 4-amino-5-substituted-1,2,4-triazole-3-thione Schiff base compounds were synthesized reacting 4-amino-5-substituted-1,2,4-triazole-3-thione with dichloro-substituted 5-pyrimidines, and the structures were verified by elemental analysis and spectroscopic techniques (FT-IR, 1H NMR). Additionally, in vitro antifungal activities of the compounds (named F1~F2; A1~A5) against Grape anthracnose and Wheat gibberellic have been evaluated. The compounds of F1, A4 and A5 were found to be potentially effective antifungal agents against Grape anthracnose, while the others showed the low bioactivity. The antifungal activity of all compounds against Wheat gibberellic were superior to that of fluconazole (standard drug, SD). Particularly, compounds of F1, A1, A4 and A5 exhibited a broad-spectrum antifungal activity against two fungus as compared to the others. Therefore, molecular docking study was carried out to explore the potential interaction between ligands and Fusarium graminearum (PDB ID: 5E9H). The results showed that four compounds had higher affinity compared with fluconazole and form the stable complex with the receptor. Besides, the frontier molecular orbitals (FMOs) and molecular electrostatic potentials (MEP) of four compounds with broad-spectrum antimicrobial activity were also calculated with DFT/ B3LYP /6-31G (d, p) method. The energy gap values (△ELUMO-HOMO) of all the synthesized compounds ranged from 3.307-3.375 eV, which was lower than that of SD (6.248 eV). Additionally, according to MEP the electrophile reaction of 5-substituted groups was beneficial to improving the biological activity against Wheat gibberellic and Grape anthracnose.

Synthesis and Antifungal Activities of Some 2,6-Bis-(Un)Substituted Phenoxymethylpyridines

2010 ◽  
Vol 65 (7-8) ◽  
pp. 433-436
Author(s):  
Hui Xu ◽  
Huan Qu
Keyword(s):  
Antifungal Activity ◽  
Fusarium Oxysporum ◽  
Fusarium Graminearum ◽  
Broad Spectrum ◽  
Alternaria Alternata ◽  
Phytopathogenic Fungi ◽  
Alternaria Brassicae ◽  
Antifungal Activities

Several 2,6-bis-(un)substituted phenoxymethylpyridines were synthesized and evaluated in vitro against Fusarium graminearum, Helminthosporium sorokinianum, Alternaria brassicae, Alternaria alternata, and Fusarium oxysporum f. sp. vasinfectum. Among all derivatives, compound 3 a exhibited a broad-spectrum antifungal activity against the five phytopathogenic fungi.

Synthesis, Molecular Docking and α-Glucosidase Inhibitory Activity Study of 2,4,6-triaryl Pyrimidine Derivatives

2020 ◽  
Vol 17 (10) ◽  
pp. 1216-1226
Author(s):  
Mohammed Hussen Bule ◽  
Roghaieh Esfandyari ◽  
Tadesse Bekele Tafesse ◽  
Mohsen Amini ◽  
Mohammad Ali Faramarzi ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Molecular Docking ◽  
Inhibitory Activity ◽  
Abdominal Distension ◽  
Spectroscopic Techniques ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Study ◽  
Enzyme Active Site ◽  
Glucosidase Inhibitors

Background: α-Glucosidase inhibitors hinder the carbohydrate digestion and play an important role in the treatment of diabetes mellitus. α-glucosidase inhibitors available on the market are acarbose, miglitol, and voglibose. However, the use of acarbose is diminishing due to related side effects like diarrhea, bloating and abdominal distension. Objectives: This study aimed to synthesize 2,4,6-triaryl pyrimidines derivatives, screen their α- glucosidase inhibitory activity, perform kinetic and molecular docking studies. Methods: A series of 2,4,6-triaryl pyrimidine derivatives were synthesized and their α-glucosidase inhibitory activity was screened in vitro. Pyrimidine derivatives 4a-m were synthesized via a twostep reaction with a yield between 49 and 93%. The structure of the synthesized compounds was confirmed by different spectroscopic techniques (IR, NMR and MS). The in vitro α-glucosidase inhibition activities of the synthesized compounds 4a-m was also evaluated against Saccharomyces cerevisiae α-glucosidase. Results and Discussion: The majority of synthesized compounds had α-glucosidase inhibitory activity. Particularly compounds 4b and 4g were the most active compounds with an IC50 value of 125.2± 7.2 and 139.8 ± 8.1 μM respectively. The kinetic study performed for the most active compound 4b revealed that the compound was a competitive inhibitor of Saccharomyces cerevisiae α-glucosidase with Ki of 122 μM. The molecular docking study also revealed that the two compounds have important binding interactions with the enzyme active site. Conclusion: 2,4,6-triarylpyrimidine derivative 4a-m were synthesized and screened for α- glucosidase inhibitory activity. Most of the synthesized compounds possess α-glucosidase inhibitory activity, and compound 4b demonstrated the most significant inhibitory action as compared to acarbose.

scholarly journals Synthesis, 3D-QSAR and Molecular Docking Study of Nopol-Based 1,2,4-Triazole-Thioether Compounds as Potential Antifungal Agents

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiu Wang ◽  
Wengui Duan ◽  
Guishan Lin ◽  
Baoyu Li ◽  
Ming Chen ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antifungal Activity ◽  
Plant Pathogens ◽  
3D Qsar ◽  
Docking Study ◽  
Qsar Model ◽  
Molecular Docking Study ◽  
Activity Data ◽  
Target Enzyme

Cytochrome bc1 complex is an important component of cellular respiratory chain, and it is also an important target enzyme to inhibit the growth of plant pathogens. Using cytochrome bc1 complex as the target enzyme, twenty-three novel nopol-based 1,2,4-triazole-thioether compounds were designed and synthesized from natural preponderant resource β-pinene, and their structures were confirmed by FT-IR, NMR, ESI-MS and elemental analysis. The in vitro antifungal activity of the target compounds 5a-5w was preliminarily evaluated against eight plant pathogens at the concentration of 50 µg/ml. The bioassay results showed that the target compounds exhibited the best antifungal activity against Physalospora piricola, in which compounds 5b (R= o-CH3 Ph), 5e (R= o-OCH3 Ph), 5h (R= o-F Ph), 5m (R= o-Br Ph), 5o (R= m,m-OCH3 Ph), and 5r (R= p-OH Ph) had inhibition rates of 91.4, 83.3, 86.7, 83.8, 91.4 and 87.3%, respectively, much better than that of the positive control chlorothalonil. Also, compound 5a (R= Ph) had inhibition rate of 87.9% against Rhizoeotnia solani, and compound 5b (R= o-CH3 Ph) had inhibition rates of 87.6 and 89% against Bipolaris maydis and Colleterichum orbicala, respectively. In order to develop novel and promising antifungal compounds against P. piricola, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was carried out using the CoMFA method on the basis of their antifungal activity data, and a reasonable and effective 3D-QSAR model (r2 = 0.944, q2 = 0.685) has been established. In addition, the theoretical study of molecular docking revealed that the target compounds could bind to and interact with the site of cytochrome bc1 complex.

scholarly journals INDOLE DERIVATIVES: DESIGN, SYNTHESIS, IN-VITRO BIOLOGICAL EVALUATION AND MOLECULAR DOCKING STUDY AS ANTICANCER AGENTS

2018 ◽  
Vol 5 (1) ◽  
pp. 28-32
Author(s):  
Amuthavalli A ◽  
Prakash B ◽  
Velmurugan R
Keyword(s):  
Molecular Docking ◽  
Anticancer Agents ◽  
Docking Study ◽  
Docking Studies ◽  
Biological Evaluation ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Standard Drug

New hetero annulated indoles were synthesized and structurally characterized by spectral means. In order to understand the nature of interactions of these molecules, we carried out molecular docking studies using the protein kinase CK2 inhibitors. The docking results provided some useful information for the futuredesign of more potent inhibitors. The in vitro cytotoxicity was evaluated for all the new compounds by MTT assay against HeLa and compared with the standard drug ellipticine. All the compounds showed moderate to potent activity against the cell lines. The preliminary structure–activity relationships were carried out.

scholarly journals Theoretical Investigation of some Antimalarial Sulfonamides as COVID-19 Drug Utilizing Computational Calculations and Molecular Docking Study

2021 ◽  
Vol 12 (1) ◽  
pp. 1208-1229
Keyword(s):  
Molecular Docking ◽  
Energy Gap ◽  
Antimalarial Activity ◽  
Theoretical Calculations ◽  
Docking Study ◽  
Mean Value ◽  
Molecular Docking Study ◽  
Active Compounds ◽  
Computational Calculations

Reactivity investigation of N-(phenylsulfonyl)acetamide derivatives with nitrogen nucleophiles to give the corresponding aminothiazole, aminooxazole, 2H-benzo[b][1,4]oxazin-3-yl, 2H-benzo[b][1,4]thiazin-3-yl, quinoxalin-2-yl, pyridin-4-ylamino, benzo[d]thiazol-2-ylthio and 1H-benzo[d]imidazol-2-ylthio derivatives; respectively. The sulphonamides were examined in vitro antimalarial activity and characterized their ADMET properties, with IC50 values of <30µ M. The synthesized sulfonamide had c-LogP values between 2 and (mean value 2.23) and MW(molecular weight) less than 400, and the common and didn’t exhibition cytotoxicity at the concentration confirmed. Sulphonamide 6a was equipped the excellent antimalarial activity through IC50=1.2µM with had the best selectivity index (9.0) due to the occurrence of quinoxaline moiety attached to the sulfonamide ring system. Additionally, the theoretical calculations of most active compounds 4a, 5c, and 6a exhibited that value of ∆ E so small which growth tendency of electron transfer from HOMO-LUMO energy gap due to existence of benzo[b][1,4]oxazin-3-yl,benzo[b][1,4]thiazin-3-yl and quinoxalin-2-yl rings attached to sulfonamide ring. Additionally, The molecular docking study of these synthesized compounds revealed small energy affinity against Plasmepsin-1 (PDBID:1j3i) and Plasmepsin-2 (PDBID:1n81) and shorter bond length. Also, the most active compounds 4a, 5c, and 6a were docked on main protease (SARS-CoV-2) (PDBID: 6lu7) and Spike Glycoprotein (SARS-CoV-2) (PDBID:6vxx) to calculate the binding energy of these fused heterocycles sulfonamides.

scholarly journals Facile Synthesis, Characterization, and In Vitro Antimicrobial Screening of a New Series of 2,4,6-Trisubstituted-s-triazine Based Compounds

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Ravi Bhushan Singh ◽  
Nirupam Das ◽  
Md. Kamaruz Zaman
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Antifungal Activity ◽  
Elemental Analysis ◽  
Broad Spectrum ◽  
Antibacterial Efficacy ◽  
Facile Synthesis ◽  
Standard Drug ◽  
E Coli

A series of new 2,4,6-trisubstituted-s-triazine was synthesized, assessed for antimicrobial activity, and characterized by FTIR, 1HNMR, 13CNMR, and elemental analysis. The tested compounds, 4d, 4g, 4h, 4k, and 4n, have shown considerable in vitro antibacterial efficacy with reference to the standard drug ciprofloxacin (MIC 3.125 μgmL−1 against B. subtilis, E. coli, and K. pneumoniae). It was observed that compounds 4d and 4h displayed equipotent antibacterial efficacy against B. subtilis (MIC 3.125 μgmL−1) and S. aureus (MIC 6.25 μgmL−1). The studies demonstrated that the para-fluorophenylpiperazine substituted s-triazine (4n) was potent and exhibited broad spectrum antibacterial activity against S. epidermidis, K. pneumoniae, and P. aeruginosa with MIC of 6.25 μgmL−1 and for E. coli, it showed an MIC of 3.125 μgmL−1 equipotent with reference to the standard drug. Among all the compounds under investigation, compound 4g also demonstrated significant antifungal activity (3.125 μgmL−1) against C. albicans.

Synthesis, In-Vitro and In-Silico Studies of Benzothiazole Azo-Ester Derivatives as Anti-TB Agents

2020 ◽  
Vol 18 (1) ◽  
pp. 15-23
Author(s):  
Mahesh Bhat ◽  
Shiddappa L. Belagali
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Assay Method ◽  
Esterification Reaction ◽  
Alamar Blue ◽  
Molecular Docking Study ◽  
Standard Drug ◽  
H37rv Strain ◽  
In Silico Studies

Introduction: A new series of benzothiazole azo-ester derivatives was synthesized by using Steglish esterification reaction. Methods: All the synthesized compounds were screened for their anti-TB activities by in-vitro microplate Alamar Blue assay method against M. tuberculosis (H37RV strain). All the compounds showed activities and their MIC values were over the range of 1.6 µg/mL to 50 µg/mL. The compounds 4d and 4j showed superior activity with MIC 1.6 µg/mL compared to the standard drug Streptomycin (MIC 6.25 µ g/mL), Pyrazinamide (MIC 3.125 µ g/mL) and Ciprofloxacin (MIC 3.125 µg/mL). Molecular docking study was carried out with enoyl acyl carrier reductase (InhA) of M. tuberculosis and decaprenyl phosphoryl-D-ribose oxidase (DprE1). Results and Conclusion: These studies showed that these compounds have more interaction with InhA protein whereas some compounds could not be docked into DprE1.

scholarly journals Isoeugenol and Hybrid Acetamides against Candida albicans Isolated from the Oral Cavity

2020 ◽  
Vol 13 (10) ◽  
pp. 291
Author(s):  
Daianne Medeiros ◽  
José Oliveira-Júnior ◽  
Jefferson Nóbrega ◽  
Laísa Cordeiro ◽  
Jeane Jardim ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Antifungal Activity ◽  
Oral Cavity ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Candida Spp ◽  
Fungal Cell ◽  
Hybrid Molecules

Isougenol is a phytoconstituent found in several essential oils. Since many natural products are potent antimicrobials, the synthesis of hybrid molecules—combining the chemical skeleton of the phytochemical with synthetic groups—can generate substances with enhanced biological activity. Based on this, the objective of this study was to evaluate the antifungal activity of isoeugenol and hybrid acetamides against Candida albicans isolated from the oral cavity. The methodologies used were the determination of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), action on fungal micromorphology, interaction test with nystatin by the checkerboard method and molecular docking study with important enzymes in the maintenance of fungal viability. The synthetic molecules did not demonstrate significant antifungal activity in vitro. The isoeugenol MIC and MFC varied between 128 and 256 µg/mL, being the phytoconstituent able to interfere in the formation of blastoconid and chlamydoconid structures, important in the pathogenic process of the species. The molecular docking study revealed that isoeugenol is a potential inhibitor of the enzymes 14-α-demethylase and delta-14-sterol reductase, interfering in the fungal cell membrane biosynthesis. Thus, this research provides clearer expectations for future pharmacological studies with isoeugenol and derived molecules, aiming at its therapeutic application against infections caused by Candida spp.

Antiprotozoal investigation of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Atalantoflavone alters the mitochondrial membrane potential

Parasitology ◽  
2019 ◽  
Vol 146 (07) ◽  
pp. 849-856
Author(s):  
Layzon Antonio Lemos da Silva ◽  
Milene Höehr de Moraes ◽  
Marcus Tullius Scotti ◽  
Luciana Scotti ◽  
Rafaela de Jesus Souza ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Membrane Potential ◽  
Trypanosoma Cruzi ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Leishmania Amazonensis ◽  
Spectroscopic Techniques ◽  
Plant Metabolites ◽  
Molecular Docking Study

AbstractThe study aims to evaluate the antiprotozoal activities of 20 plant metabolites on Trypanosoma cruzi and Leishmania amazonensis amastigotes. Compounds 1–20 were obtained and identified by using chromatographic and spectroscopic techniques. The antiparasitic assays were performed on the intracellular form of T. cruzi and L. amazonensis using human leukaemic THP-1 cells as the host. The mechanism of action of the most active compounds was explored in silico by molecular docking using T. cruzi trypanothione reductase (TR) as a target, whereas the in vitro studies were performed by enzymatic assay using T. cruzi recombinant TR. In addition, the mitochondrial membrane potential was evaluated by flow cytometry. Two flavonoids, one triterpene and three acetogenins showed from high to moderate trypanocidal activities with IC50 values ranging 3.6–37.2 µm while three of the metabolites were moderately leishmanicidal. The molecular docking study revealed interactions between TR and the most trypanocidal compounds 1 (abyssinone IV) and 2 (atalantoflavone). In contrast, both showed no effect on TR in vitro. For the mitochondrial membrane potential assay, atalantoflavone (2) displayed a dose-dependent depolarization. On the basis of the aforementioned results, this compound's structure could be chemically explored in order to develop more potent trypanocidal derivatives.

scholarly journals Synthesis of Benzimidazole–Based Analogs as Anti Alzheimer’s Disease Compounds and Their Molecular Docking Studies

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4828
Author(s):  
Bushra Adalat ◽  
Fazal Rahim ◽  
Muhammad Taha ◽  
Foziah J. Alshamrani ◽  
El Hassane Anouar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Schiff Bases ◽  
Docking Studies ◽  
Acetylcholinesterase Inhibition ◽  
Spectroscopic Techniques ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Docking Simulations ◽  
Ic50 Values

We synthesized 10 analogs of benzimidazole-based thiosemicarbazide 1 (a–j) and 13 benzimidazole-based Schiff bases 2 (a–m), and characterized by various spectroscopic techniques and evaluated in vitro for acetylcholinesterase (AchE) and butyrylcholinesterase (BchE) inhibition activities. All the synthesized analogs showed varying degrees of acetylcholinesterase and butyrylcholinesterase inhibitory potentials in comparison to the standard drug (IC50 = 0.016 and 4.5 µM. Amongst these analogs 1 (a–j), compounds 1b, 1c, and 1g having IC50 values 1.30, 0.60, and 2.40 µM, respectively, showed good acetylcholinesterase inhibition when compared with the standard. These compounds also showed moderate butyrylcholinesterase inhibition having IC50 values of 2.40, 1.50, and 2.40 µM, respectively. The rest of the compounds of this series also showed moderate to weak inhibition. While amongst the second series of analogs 2 (a–m), compounds 2c, 2e, and 2h having IC50 values of 1.50, 0.60, and 0.90 µM, respectively, showed moderate acetylcholinesterase inhibition when compared to donepezil. Structure Aactivity Relation of both synthesized series has been carried out. The binding interactions between the synthesized analogs and the enzymes were identified through molecular docking simulations.

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