scholarly journals In Vitro and In Silico Cytotoxic and Antibacterial Activities of a Diterpene from Cousinia alata Schrenk

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Almira Zhanzhaxina ◽  
Yerlan Suleimen ◽  
Ahmed M. Metwaly ◽  
Ibrahim H. Eissa ◽  
Eslam B. Elkaeed ◽  
...  
Keyword(s):  
Cytotoxic Activity ◽  
Salmonella Enteritidis ◽  
Binding Free Energy ◽  
Hdac Inhibitors ◽  
Docking Study ◽  
Artemia Salina ◽  
Wild Plant ◽  
Molecular Docking Study ◽  
2D Nmr Spectroscopy

A biologically guided isolation of secondary metabolites from Cousinia alata Schrenk wild plant growing in Akmola region, Kazakhstan, led to the isolation of the bioactive diterpene grindelic acid (1). Six flavonoids were also isolated and identified as retusine (2), pachipodol (3), jaranol (4), penduletin (5), casticin (6), and 5, 7, 3′-trihydroxy-3, 4′-dimethoxyflavone (7). Penduletin (5) showed moderate cytotoxic activity assay. Grindelic acid exhibited promising cytotoxic activity against the Artemia salina nauplii and antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Salmonella enteritidis. The presence of the essential pharmacophoric features of histone deacetylase (HDAC) inhibitors in the structure of grindelic acid encouraged us to run a molecular docking study against the HDAC enzyme to understand its mechanism of action on a molecular level. Grindelic acid showed a binding mode of interaction similar to that of the cocrystallized ligand and exhibited good binding affinity against HDAC with the binding free energy of −18.70 kcal/mol. The structures of isolated compounds were determined by MS, 1D, and 2D NMR spectroscopy methods. Compounds (1–7) were isolated for the first time from Cousinia genus.

CYTOTOXIC ACTIVITY AND MOLECULAR DOCKING STUDY OF 4- SUBSTITUTED FLAVYLIUM SALT

2021 ◽  
Author(s):  
Dejan A. Milenković ◽  
◽  
Marko N. Živanović ◽  
Milan S. Dekić ◽  
Marijana Stanojević Pirković ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Cytotoxic Activity ◽  
Data Bank ◽  
Docking Study ◽  
Binding Pocket ◽  
In Vitro Cytotoxicity ◽  
Molecular Docking Study ◽  
Binding Pockets ◽  
Hct 116

In the present manuscript, the cytotoxic activity of flavylium cation substituted at 4- position with phenyl (FC-4Ph) was tested to two cells lines (human colorectal carcinoma, HCT-116, and human fibroblast lung, MRC-5). In vitro cytotoxicity experiments were performed to elucidate the possible anticancer activity of tested substance. Investigated compound did not show cytotoxic effect on HCT-116 after 24 h, while after 72 h exerted significant effect. A significant selectivity towards colorectal carcinoma cells was observed. On the other hand, this compound did not show any effect on MRC-5 cell line. The molecular interactions between receptor tyrosine kinase (RTK) and title compound was examined. The crystal structure of investigated receptor RTK was downloaded from Protein Data Bank. The native bound ligand ((E)-[4-(3,5-difluorophenyl)-3H-pyrrolo[2,3-b]pyridin-3-ylidene](3- methoxyphenyl)methanol was extracted from receptor and binding pocket analysis was performed. Re-docking was carried out with the FC-4Ph in order to generate the same docking pose as found in co-crystallized form of receptor. The obtained results of revealed that investigated compound binds at the same binding pockets to RTK, as well as native bound ligand, by weak non-covalent interactions. The most prominent interactions are hydrogen bonds, π-alkyl, and π-π interactions. The preliminary results suggest that investigated compound showed good binding affinity against RTK, as evident from the free binding energy (ΔGbind in kJ/mol).

scholarly journals Design, Synthesis, Antitumor Activity and Molecular Docking Study of Novel 5-Deazaalloxazine Analogs

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2518
Author(s):  
Sawsan Mahmoud ◽  
Doaa Samaha ◽  
Mosaad S. Mohamed ◽  
Nageh A. Abou Taleb ◽  
Mohamed A. Elsawy ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Tumor Cell ◽  
Cell Lines ◽  
Antitumor Agents ◽  
Binding Free Energy ◽  
Docking Study ◽  
Tumor Cell Lines ◽  
Molecular Docking Study ◽  
Mcf 7

Protein tyrosine kinases (PTKs) are the most potential therapeutic targets for cancer. Herein, we present a sound rationale for synthesis of a series of novel 2-(methylthio), 2-(substituted alkylamino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives by applying structure-based drug design (SBDD) using AutoDock 4.2. Their antitumor activities against human CCRF-HSB-2, KB, MCF-7 and HeLa have been investigated in vitro. Many 5-deazaalloxazine analogs revealed high selective activities against MCF-7 tumor cell lines (IC50: 0.17–2.17 µM) over HeLa tumor cell lines (IC50 > 100 µM). Protein kinase profiling revealed that compound 3h induced multi- targets kinase inhibition including −43% against (FAK), −40% against (CDKI) and −36% against (SCR). Moreover, the Annexin-V/PI apoptotic assay elucidate that compound 3h showed 33% and potentially 140% increase in early and late apoptosis to MCF-7 cells respectively, compared to the control. The structure-activity relationship (SAR) and molecular docking study using PTK as a target enzyme for the synthesized 7-deazaalloaxazine derivatives were investigated as potential antitumor agents. The AutoDock binding affinities of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46) revealed reasonable correlations between their AutoDock binding free energy and IC50.

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.

Structure-Based Design, Synthesis, Biological Evaluation and Molecular Docking Study of 4-Hydroxy-N'-methylenebenzohydrazide Derivatives Acting as Tyrosinase Inhibitors with Potentiate Anti-Melanogenesis Activities

2020 ◽  
Vol 16 (7) ◽  
pp. 892-902 ◽  
Author(s):  
Aida Iraji ◽  
Mahsima Khoshneviszadeh ◽  
Pegah Bakhshizadeh ◽  
Najmeh Edraki ◽  
Mehdi Khoshneviszadeh
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Docking Study ◽  
Biological Evaluation ◽  
Primary Response ◽  
Ratio Method ◽  
Molecular Docking Study ◽  
Metal Chelating

Background: Melanogenesis is a process of melanin synthesis, which is a primary response for the pigmentation of human skin. Tyrosinase is a key enzyme, which catalyzes a ratelimiting step of the melanin formation. Natural products have shown potent inhibitors, but some of these possess toxicity. Numerous synthetic inhibitors have been developed in recent years may lead to the potent anti– tyrosinase agents. Objective: A number of 4-hydroxy-N'-methylenebenzohydrazide analogues with related structure to chalcone and tyrosine were constructed with various substituents at the benzyl ring of the molecule and evaluate as a tyrosinase inhibitor. In addition, computational analysis and metal chelating potential have been evaluated. Methods: Design and synthesized compounds were evaluated for activity against mushroom tyrosinase. The metal chelating capacity of the potent compound was examined using the mole ratio method. Molecular docking of the synthesized compounds was carried out into the tyrosine active site. Results: Novel 4-hydroxy-N'-methylenebenzohydrazide derivatives were synthesized. The two compounds 4c and 4g showed an IC50 near the positive control, led to a drastic inhibition of tyrosinase. Confirming in vitro results were performed via the molecular docking analysis demonstrating hydrogen bound interactions of potent compounds with histatidine-Cu+2 residues with in the active site. Kinetic study of compound 4g showed competitive inhibition towards tyrosinase. Metal chelating assay indicates the mole fraction of 1:2 stoichiometry of the 4g-Cu2+ complex. Conclusion: The findings in the present study demonstrate that 4-Hydroxy-N'- methylenebenzohydrazide scaffold could be regarded as a bioactive core inhibitor of tyrosinase and can be used as an inspiration for further studies in this area.

Spirocyclohexadienones as an Uncommon Scaffold for Acetylcholinesterase Inhibitory Activity

2019 ◽  
Vol 15 (4) ◽  
pp. 373-382 ◽  
Author(s):  
Ralph C. Gomes ◽  
Renata P. Sakata ◽  
Wanda P. Almeida ◽  
Fernando Coelho
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Population Aging ◽  
Acetylcholinesterase Inhibitors ◽  
Acetylcholinesterase Activity ◽  
Docking Study ◽  
Biological Properties ◽  
Ache Inhibitor ◽  
Molecular Docking Study

Background: The most important cause of dementia affecting elderly people is the Alzheimer’s disease (AD). Patients affected by this progressive and neurodegenerative disease have severe memory and cognitive function impairments. Some medicines used for treating this disease in the early stages are based on inhibition of acetylcholinesterase. Population aging should contribute to increase the cases of patients suffering from Alzheimer's disease, thus requiring the development of new therapeutic entities for the treatment of this disease. Methods: The objective of this work is to identify new substances that have spatial structural similarity with donepezil, an efficient commercial drug used for the treatment of Alzheimer's disease, and to evaluate the capacity of inhibition of these new substances against the enzyme acetylcholinesterase. Results: Based on a previous results of our group, we prepared a set of 11 spirocyclohexadienones with different substitutions patterns in three steps and overall yield of up to 59%. These compounds were evaluated in vitro against acetylcholinesterase. We found that eight of them are able to inhibit the acetylcholinesterase activity, with IC50 values ranging from 0.12 to 12.67 µM. Molecular docking study indicated that the spirocyclohexadienone, 9e (IC50 = 0.12 µM), a mixedtype AChE inhibitor, showed a good interaction at active site of the enzyme, including the cationic (CAS) and the peripheral site (PAS). Conclusion: We described the first study aimed at investigating the biological properties of spirocyclohexadienones as acetylcholinesterase inhibitors. Thus, we have identified an inhibitor, which provided valuable insights for further studies aimed at the discovery of more potent acetylcholinesterase inhibitors.

Novel coumarin containing dithiocarbamate derivatives as potent α-glucosidase inhibitors for management of type 2 diabetes

2020 ◽  
Vol 16 ◽  
Author(s):  
Marjan Mollazadeh ◽  
Maryam Mohammadi-Khanaposhtani ◽  
Yousef Valizadeh ◽  
Afsaneh Zonouzi ◽  
Mohammad Ali Faramarzi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kinetic Study ◽  
Active Site ◽  
Docking Study ◽  
Secondary Amines ◽  
Molecular Docking Study ◽  
Glucosidase Inhibitors ◽  
Dithiocarbamate Derivatives

Background: α-Glucosidase is a hydrolyze enzyme that plays a crucial role in degradation of carbohydrates and starch to glucose. Hence, α-glucosidase is an important target in the carbohydrate mediated diseases such as diabetes mellitus. Objective: In this study, novel coumarin containing dithiocarbamate derivatives 4a-n were synthesized and evaluated against α-glucosidase in vitro and in silico. Methods: These compounds were obtained of reaction between 4-(bromomethyl)-7-methoxy-2H-chromen-2-one 1, carbon disulfide 2, and primary or secondary amines 3a-n in the presence potassium hydroxide and ethanol at room temperature. In vitro α-glucosidase inhibition and kinetic study of these compounds were performed. Furthermore, docking study of the most potent compounds was also performed by Auto Dock Tools (version 1.5.6). Results: Obtained results showed that all the synthesized compounds exhibited prominent inhibitory activities (IC50 = 85.0 ± 4.0-566.6 ± 8.6 μM) in comparison to acarbose as standard inhibitor (IC50 = 750.0 ± 9.0 µM). Among them, secondary amine derivative 4d with pendant indole group was the most potent inhibitor. Enzyme kinetic study of the compound 4d revealed that this compound compete with substrate to connect to the active site of α-glucosidase and therefore is a competitive inhibitor. Also, molecular docking study predicted that this compound as well interacted with α-glucosidase active site pocket. Conclusion: Our results suggest that the coumarin-dithiocarbamate scaffold can be a promising lead structure for design potent α-glucosidase inhibitors for treatment of type 2 diabetes.

Synthesis, SAR, In-Silico appraisal and Anti-Microbial Study of substituted 2-aminobenzothiazoles derivatives

2019 ◽  
Vol 15 ◽  
Author(s):  
Devidas G. Anuse ◽  
Suraj N. Mali ◽  
Bapu R. Thorat ◽  
Ramesh S. Yamgar ◽  
Hemchandra K. Chaudhari
Keyword(s):  
Antimicrobial Activity ◽  
In Silico ◽  
Docking Study ◽  
Moderate Activity ◽  
Molecular Docking Study ◽  
Mass Spectral ◽  
Gram Positive Bacteria ◽  
Ft Ir ◽  
In Silico Molecular Docking

Background: Antimicrobial resistance is major global health problem, which is being rapidly deteriorating the quality of human health. Series of substituted N-(benzo[d]thiazol-2-yl)-2-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)acetamide (3a-j) were synthesized from substituted N-(benzo[d]thiazol-2-yl)-2-chloroacetamide/bromopropanamide (2a-j) and 6-fluoro-3-(piperidin-4-yl)benzo[d]isoxazole (2) and further evaluated for their docking properties and antimicrobial activity. Methods: All synthesized compounds were characterized by FT-IR, NMR and Mass spectral analysis. All compounds were allowed to dock against different antimicrobial targets having PDB ID: 1D7U and against common antifungal target having PDB ID: 1EA1. Results: The compounds 3d and 3h were showed good activity against Methicillin-resistant Staphylococcus aureus (MRSA, resistance Gram-positive bacteria). All synthesized compounds showed good to moderate activity against selected bacterial and fungal microbial strains. If we compared the actual in-vitro antimicrobial activity and in-silico molecular docking study, we found that molecules 3i and 3h were more potent than the others. Conclusion: Our current study would definitely pave the new way towards designing and synthesis of more potent 2-aminobenzothiazoles derivatives.

scholarly journals Design, synthesis, molecular docking, and in vitro α-glucosidase inhibitory activities of novel 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines against yeast and rat α-glucosidase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fariba Peytam ◽  
Ghazaleh Takalloobanafshi ◽  
Toktam Saadattalab ◽  
Maryam Norouzbahari ◽  
Zahra Emamgholipour ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Rat Small Intestine ◽  
Molecular Docking Study ◽  
Design Synthesis ◽  
Mild Conditions ◽  
Glucosidase Inhibitors ◽  
Inhibitory Activities

AbstractIn an attempt to find novel, potent α-glucosidase inhibitors, a library of poly-substituted 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines 3a–ag have been synthesized through heating a mixture of 2-aminobenzimidazoles 1 and α-azidochalcone 2 under the mild conditions. This efficient, facile protocol has been resulted into the desirable compounds with a wide substrate scope in good to excellent yields. Afterwards, their inhibitory activities against yeast α-glucosidase enzyme were investigated. Showing IC50 values ranging from 16.4 ± 0.36 µM to 297.0 ± 1.2 µM confirmed their excellent potency to inhibit α-glucosidase which encouraged us to perform further studies on α-glucosidase enzymes obtained from rat as a mammal source. Among various synthesized 3-amino-2,4-diarylbenzo[4,5]imidazo[1,2-a]pyrimidines, compound 3k exhibited the highest potency against both Saccharomyces cerevisiae α-glucosidase (IC50 = 16.4 ± 0.36 μM) and rat small intestine α-glucosidase (IC50 = 45.0 ± 8.2 μM). Moreover, the role of amine moiety on the observed activity was studied through substituting with chlorine and hydrogen resulted into a considerable deterioration on the inhibitory activity. Kinetic study and molecular docking study have confirmed the in-vitro results.

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