Fungicides Inhibition Analysis by Molecular Docking and Sensitivity Testing of Penicillium italicum

Blue mold, caused by Penicillium. italicum, is one of the most damaging postharvest diseases of citrus fruit. P. italicum Sterol 14α-demethylase (PiCYP51), an important enzyme in membrance sterol biosynthesis, is a key target of antifungal compounds for citrus disease caused by P. italicum. The three-dimensional structure of PiCYP51 from P. italicum Chinese isolate (HS-1) was constructed through homology modeling basing on the crystal structure of human CYP51. After molecular dynamics (MD) simulation, the refined model was assessed by PROCHECK on the quality. Following evaluation on the reliability was performed by investigating the binding interaction of two commercial sterol 14α-demethylase inhibitors (DMIs) with the enzyme. The binding mode predicted by the molecular docking revealed that the DMIs interacted with PiCYP51 mainly through hydrogen-bonding and hydrophobic interactions. Furthermore, the results were compatible with the detected EC50 values, which were determined as 0.25 and 0.31mg/L for tebuconazole and diniconazole. The binding mode of antifungal agents with PiCYP51 can provide references for DMIs optimization, virtual screening, or de novo antifungal compounds design.

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MOLECULAR DOCKING: AN EXPLANATORY APPROACH IN STRUCTURE-BASED DRUG DESIGNING AND DISCOVERY

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2021v13i6.40830 ◽

2021 ◽

pp. 6-12

Author(s):

ADITI SHARMA ◽

SALONI KUNWAR ◽

VAISHALI ◽

VAISHALI AGARWAL ◽

CHHAYA SINGH ◽

...

Keyword(s):

Molecular Docking ◽

Drug Design ◽

De Novo ◽

Scoring Function ◽

Binding Mode ◽

De Novo Drug Design ◽

Structure Based Drug Design ◽

Binding Characteristics ◽

Stable Product ◽

Novel Concept

Molecular docking is a modeling tool of Bioinformatics which includes two or more molecules which interact to provide a stable product in the form of a complex. Molecular docking is helpful in predicting the 3-d structure of a complex which depends on the binding characteristics of Ligand and target. Also, it is a structure-based virtual screening (SBVS) utilized to keep the 3-d structures of small molecule which are generated by computers into a target structure in various types of conformations, positions and orientations. This molecular docking has come out to be a novel concept with various types of advantages. It behaves as a highly exploring domain due to its significant structure-based drug design (SBDD), Assessment of Biochemical pathways, Lead Optimization and in De Novo drug design. In spite of all potential approaches, there are certain challenges which are-scoring function (differentiate the true binding mode), ligand chemistry (tautomerism and ionization) and receptor flexibility (single conformation of rigid receptor). The area of computer-aided drug design and discovery (CADDD) has achieved large favorable outcomes in the past few years. CADD has been adopted by various big pharmaceutical companies for leading discoveries of drugs. Many researchers have worked in order to examine different docking algorithms and to predict molecules' active site. Hence, this Review article depicts the whole sole of Molecular Docking.

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Homology Modeling of Aeromonas hydrophila Laccase and its Molecular Docking with the 2,5-Xylidine

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.798-799.83 ◽

2013 ◽

Vol 798-799 ◽

pp. 83-86

Author(s):

Dong Xia Du ◽

Shi Ping Shan ◽

De Yuan Zhang ◽

Yue Lin He

Keyword(s):

Molecular Docking ◽

Homology Modeling ◽

Aeromonas Hydrophila ◽

Three Dimensional ◽

Industrial Effluents ◽

Binding Pocket ◽

Binding Mode ◽

Major Effect ◽

Dimensional Structure ◽

Three Dimensional Structure

Laccases belonging to multicopper oxidase family oxidize a broad range of reducing substrates, especially industrial effluents-derived polyphenols, which causing major effect on human health as well as environment. In order to investigate the molecular mechanism of interaction between laccase and its substrate, it is a good idea to analyze three-dimensional structure of laccase. Based on crystal structure ofEscherichia colilaccase CueO, the three-dimensional structure ofAeromonas hydrophilaLaccase (Ah-lac) was constructed by homology modeling and further evaluated using PROSA energy and ERRAT. The substrate binding site in Ah-lac was predicted and the binding mode of 2,5-Xylidine as a putative ligand to Ah-lac was presented using molecular docking. The residues of Met378 and His382 in the binding pocket are responsible for the interactions with 2,5-Xylidine via two hydrogen bonds. The two residues could be important for substrate recognition.

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Design, Synthesis, Molecular Docking and Biological Evaluation of 1-(benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol Derivatives as Antiproliferative Agents

Letters in Organic Chemistry ◽

10.2174/1570178616666190408101233 ◽

2019 ◽

Vol 16 (10) ◽

pp. 837-845

Author(s):

Sandhya Jonnala ◽

Bhaskar Nameta ◽

Murthy Chavali ◽

Rajashaker Bantu ◽

Pallavi Choudante ◽

...

Keyword(s):

Molecular Docking ◽

Inhibitory Activity ◽

Chinese Hamster Ovary Cells ◽

Chinese Hamster ◽

Mouse Skin ◽

Coupling Reaction ◽

Binding Mode ◽

Biological Evaluation ◽

Design Synthesis

A class of 1-((benzo[d]thiazol-2-ylamino)(phenyl)methyl)naphthalen-2-ol derivatives (4a-t) has been synthesized in good yields through a three component coupling reaction. The newly synthesized compounds were evaluated for their in vitro antiproliferative activity against five cell lines such as DU145 (human prostate cancer), MDA-MB-B231 (human breast cancer), SKOV3 (human ovarian cancer), B16-F10 (mouse skin melanoma) and CHO-K1 (Chinese hamster ovary cells), a noncancerous cell line. In vitro inhibitory activity indicates that compounds 4a, 4b, 4c, 4d, 4g, 4j, and 4o exhibited potent anti-proliferative behavior. Among them, compounds 4g, 4j and 4o found to be the most active members exhibiting remarkable growth inhibitory activity. Molecular docking facilitates to investigate the probable binding mode and key active site interactions in tubulins α and β proteins. The docking results are complementary to experimental results.

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Molecular Docking Analysis of Flavonoid Compounds with Matrix Metalloproteinase-8 for the Identification of Potential Effective Inhibitors

Letters in Drug Design & Discovery ◽

10.2174/1570180817999200831094703 ◽

2020 ◽

Vol 17 ◽

Author(s):

Amir Taherkhani ◽

Athena Orangi ◽

Shirin Moradkhani ◽

Zahra Khamverdi

Keyword(s):

Amino Acids ◽

Molecular Docking ◽

Amino Acid ◽

Matrix Metalloproteinase ◽

Ligand Binding ◽

Chronic Inflammation ◽

Cancer Progression ◽

Dimensional Structure ◽

Control Test ◽

Therapeutic Procedures

Background: Matrix metalloproteinase-8 (MMP-8) participates in degradation of different types of collagens in the extracellular matrix and basement membrane. Up-regulation of the MMP-8 has been demonstrated in many of disorders including cancer development, tooth caries, periodontal/peri-implant soft and hard tissue degeneration, and acute/chronic inflammation. Therefore, MMP-8 has become an encouraging target for therapeutic procedures for scientists. We carried out molecular docking approach to study the binding affinity of 29 flavonoids, as drug candidates, with the MMP-8. Pharmacokinetic and toxicological properties of the compounds were also studied. Moreover, it was attempted to identify the most important amino acids participating in ligand binding based on degree of each of the amino acids in the ligand-amino acid interaction network for MMP-8. Methods: Three-dimensional structure of the protein was gained from the RCSB database (PDB ID: 4QKZ). AutoDock version 4.0 and Cytoscape 3.7.2 were used for molecular docking and network analysis, respectively. Notably, the inhibitor of the protein in the crystalline structure of the 4QKZ was considered as a control test. Pharmacokinetic and toxicological features of compounds were predicted using bioinformatic web tools. Post-docking analyses were performed using BIOVIA Discovery Studio Visualizer version 19.1.0.18287. Results and Discussions: According to results, 24 of the studied compounds considered to be top potential inhibitors for MMP-8 based on their salient estimated free energy of binding and inhibition constant as compared with the control test: Apigenin-7-glucoside, nicotiflorin, luteolin, glabridin, taxifolin, apigenin, licochalcone A, quercetin, isorhamnetin, myricetin, herbacetin, kaemferol, epicatechin, chrysin, amentoflavone, rutin, orientin, epiafzelechin, quercetin-3-rhamnoside, formononetin, isoliquiritigenin, vitexin, catechine, isoquercitrin. Moreover, His-197 was found to be the most important amino acid involved in the ligand binding for the enzyme. Conclusion: The results of the current study could be used in the prevention and therapeutic procedures of a number of disorders such as cancer progression and invasion, oral diseases, and acute/chronic inflammation. Although, in vitro and in vivo tests are inevitable in the future.

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Synthesis, In-vitro and Docking Analysis of C-3 substituted Coumarin Analogues as Anticancer Agents C-3 Substituted Coumarins as Anticancer Agents

Current Computer - Aided Drug Design ◽

10.2174/1573409916666200120114641 ◽

2020 ◽

Vol 16 ◽

Author(s):

Anuradha Thakur ◽

Kamalpreet Kaur ◽

Praveen Sharma ◽

Ramit Singla ◽

Sandeep Singh ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Docking ◽

Cancer Cell ◽

Breast Cancer Cell ◽

Anticancer Agents ◽

Proliferative Activity ◽

Binding Interaction ◽

Diverse Range ◽

Mcf 7 ◽

Substituted Coumarins

Background: Breast cancer (BC) is a leading cause of cancer-related deaths in women next to skin cancer. Estrogen receptors (ERs) play an important role in the progression of BC. Current anticancer agents have several drawbacks such as serious side effects and the emergence of resistance to chemotherapeutic drugs. As coumarins possess minimum side effect along with multi-drug reversal activity, it has a tremendous ability to regulate a diverse range of cellular pathways that can be explored for selective anticancer activity. Objectives: Synthesis and evaluation of new coumarin analogues for anti-proliferative activity on human breast cancer cell line MCF-7 along with exploration of binding interaction of the compounds for ER-α target protein by molecular docking. Method: In this study, the anti-proliferative activity of C-3 substituted coumarins analogues (1-17) has been evaluated against estrogen receptor-positive MCF-7 breast cancer cell lines. Molecular interactions and ADME study of the compounds were analyzed by using Schrodinger software. Results: Among the synthesized analogues 12 and 13 show good antiproliferative activity with IC50 values 1and 1.3 µM respectively. Molecular docking suggests a remarkable binding pose of all the seventeen compounds. Compounds 12 and 13 were found to exhibit dock score of -4.10 kcal/mol and -4.38 kcal/mol respectively. Conclusion: Compounds 12 and 13 showed the highest activity followed by 1 and 5. ADME properties of all compounds were in the acceptable range. The active compounds can be taken for lead optimization and mechanistic interventions for their in vivo study in the future.

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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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