scholarly journals New Benzoxazole Derivatives as Antiprotozoal Agents: In Silico Studies, Synthesis, and Biological Evaluation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Mohamed A. Abdelgawad ◽  
Mohammad M. Al-Sanea ◽  
Mohamed A. Zaki ◽  
Enas I. A. Mohamed ◽  
Shabana I. Khan ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Antimalarial Activity ◽  
Biological Activities ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Chromatographic Separations ◽  
Major Mechanism ◽  
In Silico Studies

Background. Benzoxazole derivatives have different biological activities. In pursuit of designing novel chemical entities with antiprotozoal and antimicrobial activities, benzoxazolyl aniline was utilized as a privileged scaffold of a series of (3-benzoxazole-2-yl) phenylamine derivatives, 3-benzoxazoloyl acetamide, and butyramide derivatives. Methods. These novel analogs were synthesized in straightforward simple chemistry without any quantitative chromatographic separations in reasonable yields. The biological evaluation of all target compounds as potential antimalarial, antileishmanial, antitrypanosomal, and antimicrobial agents was performed by various well-established cell-based methods. Results. Compounds 6d and 5a showed promising biological screening data. The amidation of 3-benzoxazolyl aniline 1 with the chloroacetyl functional group resulted in a good antimalarial activity and showed moderate inhibitory activities against leishmanial and trypanosomal spp. Moreover, chloroacetyl functionalization of benzoxazolyl aniline serves as a good early goal for constructing and synthesizing new antimicrobial and antiprotozoal agents. The molecular docking study rationalizes the relative inhibitory activity of compound 5a as an antimalarial agent with the deregulation of PfPNP activity which has emerged as a major mechanism of these targets.

Synthesis, Antimicrobial Evaluation and Docking Study of Novel Thiosemicarbazone clubbed with 1,2,3-Triazoles

2020 ◽  
Vol 16 ◽  
Author(s):  
Adinath D. Badar ◽  
Shubham M. Sulakhe ◽  
Mahesh B. Muluk ◽  
Naziya N. M. A. Rehman ◽  
Prashant P. Dixit ◽  
...  
Keyword(s):  
Binding Affinity ◽  
Biological Activities ◽  
Dna Gyrase ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Diffusion Method ◽  
Molecular Docking Study ◽  
Triazole Derivatives ◽  
Antibacterial And Antifungal

Background: Thiosemicarbazone, 1,2,3-triazole and their derivatives received great pharmaceutical importance due to their prominent biological activities. In the present study, the molecular hybrid thiosemicarbazone-1,2,3-triazoles derivatives were synthesized and screened for their antimicrobial activities. Methods: A series of thiosemicarbazone clubbed with 1,2,3-triazole derivatives were synthesized via click chemistry approach in good yields. The structures of synthesized compounds were assigned by their spectral data. The in vitro antimicrobial activity was performed by the agar well diffusion method. A molecular docking study was performed to identify the possible mode of action of synthesized derivatives. Results: The compounds 5d, 5h, 5i and 5k have exhibited excellent antimicrobial activities against both antibacterial and antifungal pathogens. The active thiosemicarbazone-1,2,3-triazole derivatives have shown excellent binding affinity towards DNA gyrase. Conclusion: The molecular hybrid thiosemicarbazone-1,2,3-triazole derivatives were synthesized. The newly synthesized compounds were evaluated for their antimicrobial activities. Few of the thiosemicarbazone-1,2,3-triazoles derivatives have exhibited good antimicrobial activities. They have been shown excellent binding affinity towards DNA gyrase.

Synthesis, Biological Evaluation and Molecular Docking Study of Pyrazole, Pyrazoline Clubbed Pyridine as Potential Antimicrobial Agents

2020 ◽  
Vol 18 (3) ◽  
pp. 306-314 ◽  
Author(s):  
Nisheeth C. Desai ◽  
Darshita V. Vaja ◽  
Krunalsinh A. Jadeja ◽  
Surbhi B. Joshi ◽  
Vijay M. Khedkar
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Biological Evaluation ◽  
Mass Spectral Data ◽  
Molecular Docking Study ◽  
Mass Spectral ◽  
Chemical Structures ◽  
Subunit B

Introduction: In continuation of our efforts to find new antimicrobials, herein we report the synthesis of various pyrazole, pyrazoline, and pyridine based novel bioactive heterocycles (3a-t). Methods: Newly synthesized compounds were analysed for their antimicrobial activity. Compounds 3c, 3h, 3i, 3k, 3n, and 3q showed significant antimicrobial activity. Results: Molecular docking study for the most active analogues against DNA gyrase subunit b (PDB ID: 1KZN) corroborated well with the observed antimicrobial potency exhibiting significant binding affinity. Conclusion: Interpretation of the chemical structures reported in this paper was based on IR, 1H NMR, 13C NMR, and mass spectral data.

scholarly journals Mechanistic Insights into Biological Activities of Polyphenolic Compounds from Rosemary Obtained by Inverse Molecular Docking

Foods ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 67
Author(s):  
Samo Lešnik ◽  
Urban Bren
Keyword(s):  
Molecular Docking ◽  
Pathogenic Bacteria ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Data Bank ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Carnosic Acid ◽  
Molecular Docking Study

Rosemary (Rosmarinus officinalis L.) represents a medicinal plant known for its various health-promoting properties. Its extracts and essential oils exhibit antioxidative, anti-inflammatory, anticarcinogenic, and antimicrobial activities. The main compounds responsible for these effects are the diterpenes carnosic acid, carnosol, and rosmanol, as well as the phenolic acid ester rosmarinic acid. However, surprisingly little is known about the molecular mechanisms responsible for the pharmacological activities of rosemary and its compounds. To discern these mechanisms, we performed a large-scale inverse molecular docking study to identify their potential protein targets. Listed compounds were separately docked into predicted binding sites of all non-redundant holo proteins from the Protein Data Bank and those with the top scores were further examined. We focused on proteins directly related to human health, including human and mammalian proteins as well as proteins from pathogenic bacteria, viruses, and parasites. The observed interactions of rosemary compounds indeed confirm the beforementioned activities, whereas we also identified their potential for anticoagulant and antiparasitic actions. The obtained results were carefully checked against the existing experimental findings from the scientific literature as well as further validated using both redocking procedures and retrospective metrics.

scholarly journals A Novel Series of Acylhydrazones as Potential Anti-Candida Agents: Design, Synthesis, Biological Evaluation and In Silico Studies

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 184 ◽  
Author(s):  
Anca-Maria Borcea ◽  
Gabriel Marc ◽  
Ioana Ionuț ◽  
Dan C. Vodnar ◽  
Laurian Vlase ◽  
...  
Keyword(s):  
In Silico ◽  
Docking Study ◽  
Biological Evaluation ◽  
Antifungal Drugs ◽  
Biologically Active ◽  
Molecular Docking Study ◽  
Candida Spp ◽  
In Silico Admet ◽  
In Silico Studies

In the context of an increased incidence of invasive fungal diseases, there is an imperative need of new antifungal drugs with improved activity and safety profiles. A novel series of acylhydrazones bearing a 1,4-phenylene-bisthiazole scaffold was designed based on an analysis of structures known to possess anti-Candida activity obtained from a literature review. Nine final compounds were synthesized and evaluated in vitro for their inhibitory activity against various strains of Candida spp. The anti-Candida activity assay revealed that some of the new compounds are as active as fluconazole against most of the tested strains. A molecular docking study was conducted in order to evaluate the binding poses towards lanosterol 14α-demethylase. An in silico ADMET analysis showed that the compounds possess drug-like properties and represent a biologically active framework that should be further optimized as potential hits.

Tetrazoloquinoline-1,2,3-Triazole Derivatives as Antimicrobial Agents: Synthesis, Biological Evaluation and Molecular Docking Study

2020 ◽  
pp. 1-22
Author(s):  
Mubarak H. Shaikh ◽  
Dnyaneshwar D. Subhedar ◽  
Satish V. Akolkar ◽  
Amol A. Nagargoje ◽  
Vijay M. Khedkar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Triazole Derivatives

scholarly journals New Series of Thiazole Derivatives: Synthesis, Structural Elucidation, Antimicrobial Activity, Molecular Modeling and MOE Docking

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1741 ◽  
Author(s):  
Ismail Althagafi ◽  
Nashwa El-Metwaly ◽  
Thoraya A. Farghaly
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Docking Study ◽  
Biological Application ◽  
Thiazole Derivatives ◽  
Molecular Docking Study ◽  
Different Types ◽  
Effective Part ◽  
Bacteria And Fungi

Based on the extensive biological activities of thiazole derivatives against different types of diseases, we are interested in the effective part of many natural compounds, so we synthesized a new series of compounds containing di-, tri- and tetrathiazole moieties. The formation of such derivatives proceeded via reaction of 2-bromo-1-(4-methyl-2-(methylamino)thiazol-5-yl)ethan-1-one with heterocyclic amines, o-aminothiophenol and thiosemicarbazone derivatives. The structure and mechanistic pathways for all products were discussed and proved based on spectral results, in addition to conformational studies. Our aim after the synthesis is to investigate their antimicrobial activity against various types of bacteria and fungi species. Preceeding such an investigation, a molecular docking study was carried out with selected conformers, as representative examples, against three pathogen-proteins. This preliminary stage could support the biological application. The potency of these compounds as antimicrobial agents has been evaluated. The results showed that derivatives which have di- and trithiazole rings displayed high activity that exceeds the used standard antibiotic.

scholarly journals Solvent-Free Synthesis, In Vitro and In Silico Studies of Novel Potential 1,3,4-Thiadiazole-Based Molecules against Microbial Pathogens

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 342
Author(s):  
Ihsan A. Shehadi ◽  
Mohamad T. T. Abdelrahman ◽  
Mohamed Abdelraof ◽  
Huda R. M. Rashdan
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Docking Study ◽  
Antimicrobial Activities ◽  
Trna Synthetase ◽  
Microbial Pathogens ◽  
Molecular Docking Study ◽  
Chemical Structures ◽  
In Silico Studies

A new series of 1,3,4-thiadiazoles was synthesized by the reaction of methyl 2-(4-hydroxy-3-methoxybenzylidene) hydrazine-1-carbodithioate (2) with selected derivatives of hydrazonoyl halide by grinding method at room temperature. The chemical structures of the newly synthesized derivatives were resolved from correct spectral and microanalytical data. Moreover, all synthesized compounds were screened for their antimicrobial activities using Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Staphylococcus aureus, and Candida albicans. However, compounds 3 and 5 showed significant antimicrobial activity against all tested microorganisms. The other prepared compounds exhibited either only antimicrobial activity against Gram-positive bacteria like compounds 4 and 6, or only antifungal activity like compound 7. A molecular docking study of the compounds was performed against two important microbial enzymes: tyrosyl-tRNA synthetase (TyrRS ) and N-myristoyl transferase (Nmt). The tested compounds showed variety in binding poses and interactions. However, compound 3 showed the best interactions in terms of number of hydrogen bonds, and the lowest affinity binding energy (–8.4 and –9.1 kcal/mol, respectively). From the in vitro and in silico studies, compound 3 is a good candidate for the next steps of the drug development process as an antimicrobial drug.

scholarly journals Hit Identification of a Novel Quinazoline Sulfonamide as a Promising EphB3 Inhibitor: Design, Virtual Combinatorial Library, Synthesis, Biological Evaluation, and Docking Simulation Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1247
Author(s):  
Kyeong Lee ◽  
Hossam Nada ◽  
Hyun Jung Byun ◽  
Chang Hoon Lee ◽  
Ahmed Elkamhawy
Keyword(s):  
Molecular Docking ◽  
Combinatorial Library ◽  
Binding Free Energy ◽  
Biological Activities ◽  
Hybrid Approach ◽  
Docking Simulation ◽  
Docking Study ◽  
Biological Evaluation ◽  
Molecular Docking Study ◽  
Hit Identification

EphB3 is a major key player in a variety of cellular activities, including cell migration, proliferation, and apoptosis. However, the exact role of EphB3 in cancer remains ambiguous. Accordingly, new EphB3 inhibitors can increase the understanding of the exact roles of the receptor and may act as promising therapeutic candidates. Herein, a hybrid approach of structure-based design and virtual combinatorial library generated 34 quinazoline sulfonamides as potential selective EphB3 inhibitors. A molecular docking study over EphB3 predicted the binding affinities of the generated library, and the top seven hit compounds (3a and 4a–f), with GlideScore ≥ −6.20 Kcal/mol, were chosen for further MM-GBSA calculations. Out of the seven top hits, compound 4c showed the highest MM-GBSA binding free energy (−74.13 Kcal/mol). To validate these predicted results, compounds 3a and 4a–f were synthesized and characterized using NMR, HRMS, and HPLC. The biological evaluation revealed compound 4c as a potent EphB3 inhibitory lead (IC50 = 1.04 µM). The screening of 4c over a mini-panel of kinases consisting of EGFR, Aurora A, Aurora B, CDK2/cyclin A, EphB1, EphB2, EphB4, ERBB2/HER2, and KDR/VEGFR2, showed a promising selective profile against EphB3 isoform. A dose-dependent assay of compound 4c and a molecular docking study over the different forms of EphB provided insights into the elicited biological activities and highlighted reasonable explanations of the selectivity.

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