scholarly journals Elucidating the Molecular Anatomy of Acetyl-CoA Carboxylase in Brassica Rapa for Evolving Climate-Resilient Interventions to Minimize Carbon Footprints

2021 ◽  
Author(s):  
Chinmaya Kumar Das ◽  
Umasankar Nayak ◽  
Preetinanda Pati
Keyword(s):  
Climate Change ◽  
Fatty Acids ◽  
Molecular Docking ◽  
Brassica Rapa ◽  
Active Site ◽  
Crop Production ◽  
Docking Studies ◽  
Molecular Models ◽  
Acetyl Coa Carboxylase ◽  
Carbon Footprints

Climate change is an emerging threat to food & nutritional security. It adversely affects crop production by altering the gene expression patterns of genes encoding for growth, development, and crop yield. Further, carbon emissions during crop production processes coupled with rapid urbanization & industrialization, and deforestation drive aggravate the climate change problem. Therefore, innovative adaptive measures must be developed in terms of climate-resilient interventions for enhancing productivity by minimizing expanding carbon footprints. In this investigation, we developed molecular models of different components (biotin carboxylase (BC), biotin carboxyl carrier protein (BCCP), and carboxyl transferase (CT)) of an important enzyme acetyl-CoA carboxylase (ACC) of Brassica rapa which play a vital role in carbon sequestration in fatty acids and regulation of fatty acid metabolism. We successfully built molecular models of BC, BCCP, CT-α, and CT-β having sufficient degree of reliability and stereochemical quality scores as obtained from the structure validation using PROCHECK, ProSA, Verify3D, and ERRAT. Further, we did a set of molecular docking studies with models of BC, BCCP, and CT (CT-α, CT-β) with their ligands (ATP, biotin, acetyl coenzyme-A) to know the active site residues involved in catalysis reaction using AutoDock-Vina. Our findings on the molecular architecture of different components of ACC in Brassica rapa and ligand binding sites of component proteins from the molecular docking studies will help in two different ways. Firstly, structural information of model would facilitate designing of site-directed mutagenesis based functional genomic studies for comprehending the putative role of ACC in fatty acid biosynthesis, regulation of ACC by light & other molecular players reported in other species such as CTI & PII proteins. Further, functional haplotype markers can be designed using active site information of ACC in Brassica rapa to improve oil content by amalgamating desired set of available genomic variations present in different cultivars and landraces using the molecular breeding programme and genome editing tools. Such findings are potential drivers for minimizing carbon footprints by sequestering carbon in carbon skeletons of fatty acids in minimal input requiring oil-producing crop plants (Brassica rapa).

scholarly journals Synthesis, Molecular Docking Studies and Antifungal Activity Evaluation of New Thiazolyl-methylen-1,3,4-oxadiazolines as Potential Lanosterol 14a-demethylase Inhibitors

2019 ◽  
Vol 70 (10) ◽  
pp. 3522-3526
Author(s):  
Smaranda Oniga ◽  
Catalin Araniciu ◽  
Gabriel Marc ◽  
Livia Uncu ◽  
Mariana Palage ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Antifungal Activity ◽  
Active Site ◽  
Docking Studies ◽  
Molecular Docking Studies ◽  
Activity Evaluation ◽  
Lanosterol Demethylase ◽  
Target Enzyme

Considering the well-established antifungal activity of azole compounds, a new series of thiazolyl-methylen-1,3,4-oxadiazolines derivatives were designed and synthesized as lanosterol-demethylase inhibitors. The final compounds were screened for antifungal activity against the Candida albicans ATCC 90028 strain. Molecular docking studies were performed to investigate the interaction modes between the compounds and the active site of lanosterol 14a-demethylase, which is a target enzyme for anticandidal azoles. Theoretical ADME predictions were also calculated for the final compounds 5a-h.

Synthesis, characterization and molecular docking studies on some new N-substituted 2-phenylpyrido[2,3-d]pyrimidine derivatives

2021 ◽  
pp. 3846-3854
Author(s):  
Vivek B. Panchabhai ◽  
Santosh R. Butle ◽  
Parag G. Ingole
Keyword(s):  
Crystal Structure ◽  
Antibacterial Activity ◽  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Biotin Carboxylase ◽  
Active Site Residues ◽  
Pyrimidine Derivatives ◽  
Molecular Docking Studies ◽  
Novel Scaffold

We report a novel scaffold of N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives with potent antibacterial activity by targeting this biotin carboxylase enzyme. The series of eighteen N-substituted 2-phenylpyrido(2,3-d)pyrimidine derivatives were synthesized, characterized and further molecular docking studied to determine the mode of binding and energy changes with the crystal structure of biotin carboxylase (PDB ID: 2V58) was employed as the receptor with compounds 6a-r as ligands. The results obtained from the simulation were obtained in the form of dock score; these values represent the minimum energies. Compounds 6d, 6l, 6n, 6o, 6r and 6i showed formation of hydrogen bonds with the active site residues and van Der Walls interactions with the biotin carboxylase enzyme in their molecular docking studies. This compound can be studied further and developed into a potential antibacterial lead molecule.

scholarly journals Synthesis and Molecular Docking Studies of some Pyrano[2,3-c] Pyrazole as an Inhibitor of SARS-Coronavirus 3CL Protease

2021 ◽  
Vol 11 (3) ◽  
pp. 3780-3801
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Antiviral Treatment ◽  
Specific Treatment ◽  
Docking Studies ◽  
Strong Hydrogen Bond ◽  
Active Site Residues ◽  
Hydrogen Bond Interaction ◽  
Main Protease ◽  
3Cl Protease

The widespread global COVID-19 pandemic due to the lack of specific treatment and the urgent situation requires the use of all resources to remedy this scourge. The current study aimed to use molecular docking tools to find potential drug candidates for treatment. The pyrano[2,3-c] pyrazole 5(a-e) was targeted against the Main protease (Mpro), which plays a vital role in the replication and transcription of the Corona viral genome. The 3CL Protease (PDB ID 6LU7) was modeled, and the compounds were docked using Autodock Vina software, and ADMET data have been studied. All synthesized compounds were well engaged into the active site of the main protease with strong hydrogen bond interaction and a good score of energy. The 5b have been classed as the best inhibitor with an energy score of -6.2 kcal/mol, similar to the one given by chloroquine (-6.2Kcal/mol). Moreover, the molecular interaction studies showed that protease structure had multiple active site residues for all studied compounds. Our finding confirms the potential of these derivatives as lead compounds against the selected target protein of coronavirus, which needs further analysis and dynamic simulation studies to propose then develop a new antiviral treatment.

Interaction of Human Alpha-2-Macroglobulin with Pesticide Aldicarb Using Spectroscopy and Molecular Docking

2020 ◽  
Vol 27 ◽  
Author(s):  
Swati Dixit ◽  
Mohammad Khalid Zia ◽  
Tooba Siddiqui ◽  
Haseeb Ahsan ◽  
Fahim Halim Khan
Keyword(s):  
Molecular Docking ◽  
Receptor Binding ◽  
Crop Production ◽  
Potato Crop ◽  
Cd Spectroscopy ◽  
Docking Studies ◽  
Binding Domain ◽  
Spectroscopic Techniques ◽  
Receptor Binding Domain ◽  
Other Substances

Background: Aldicarb is a carbamate pesticide commercially used in potato crop production. Once it enters human body, it interacts with diverse proteins and other substances. Objective: Aldicarb is toxic to human health and it is also a cholinesterase inhibitor, which prevents the breakdown of acetylcholine in synapse. Human alpha-2-macroglobulin (α2M), is a large tetrameric glycoprotein of 720 kDa with antiproteinase activity, found abundantly in plasma. Methods: In the present study, the interaction of aldicarb with alpha-2-macroglobulin was explored utilizing various spectroscopic techniques and molecular docking studies. Results: UV-vis and fluorescence spectroscopy suggests the formation of a complex between aldicarb and α2M apparent by increased absorbance and decreased fluorescence with static quenching mode. CD spectroscopy indicates a slight change in the structure of alpha-2-macroglobulin. Docking studies confirm the interaction of aldicarb with Pro- 1391, Leu-1392, Lys1393, Val-1396, Lys- 1397, Thr-1408, Glu-1409, Val-1410, Asp-282 and Glu-281 in the receptor binding domain at the Cterminal of the alpha 2 macroglobulin. Discussion: In this work, aldicarb is shown to bind with alpha 2-macroglobulin at receptor binding domain which is the binding site for various extracellular and intracellular ligand too. Also, affecting the functional activity of the protein may lead to further physiological consequences. Conclusion: It is possible that aldicarb binds and compromises antiproteinase activity of α2M and binding properties by inducing changes in the secondary structure of the protein.

Synthesis of New Bis-pyrazolines Endowed with Potent Antifungal Activity against Candida albicans and Aspergillus niger

2020 ◽  
Vol 17 ◽  
Author(s):  
Belgin Sever ◽  
Mehlika Dilek Altıntop ◽  
Ahmet Özdemir
Keyword(s):  
Candida Albicans ◽  
Molecular Docking ◽  
Antifungal Activity ◽  
Aspergillus Niger ◽  
Mtt Assay ◽  
Active Site ◽  
Antifungal Agents ◽  
Docking Studies ◽  
Antifungal Effects ◽  
Nih 3T3

Background: Due to the increasing number of cases of invasive fungal infections (IFIs), there is an urgent need to identify potent antifungal agents capable of combating IFIs. Pyrazolines are one such class of therapeutically active agents that could be considered to fulfil this need. Objective: In this context, this paper aims to identify two new series of bis-pyrazolines endowed with potent antifungal activity against Candida albicans and Aspergillus niger. Methods: Two new series of bis-pyrazolines (4a-i, 5a-e) were synthesized through an efficient and and versatile synthetic procedure. The compounds were screened for their antifungal effects on C. albicans and A. niger using a broth microdilution method. Their cytotoxic effects on NIH/3T3 mouse embryonic fibroblast cell line were determined using MTT assay. Molecular docking studies were performed in the active site of lanosterol 14α-demethylase (CYP51) to shed light on their antifungal effects using Schrödinger’s Maestro molecular modeling package. Results And Discussion: 5,5'-(1,4-Phenylene)bis[1-(2-(5-phenyl-1,3,4-oxadiazol-2-yl)thio)acetyl)-3-(2-thienyl)-4,5- dihydro-1H-pyrazole] (4a) and 5,5'-(1,4-phenylene)bis[1-(2-(4-(2-hydroxyethyl)-1-piperazinylthiocarbamoyl)thio)acetyl)-3- (2-thienyl)-4,5-dihydro-1H-pyrazole] (5a) were found as the most promising antifungal agents in this series. Compounds 4a and 5a showed pronounced antifungal activity against C. albicans (MIC= 0.016 mg/mL) and A. niger (MIC= 0.008 mg/mL). Based on MTT assay, their antifungal effects were selective (IC50 > 0.500 mg/mL for NIH/3T3 cell line). Molecular docking studies suggested that compounds 5a-e might show their anticandidal effects via CYP51 inhibition in regard to their stronger interactions in the active site of CYP51. Conclusion: Compounds 4a and 5a stand out as potential antifungal agents for the management of IFIs caused by C. albicans and A. niger.

Enzyme Inhibition, Kinetic, and Molecular Docking Studies of α-glucosidase

2020 ◽  
Vol 16 (2) ◽  
pp. 155-161
Author(s):  
Ebrahim S. Moghadam ◽  
Mohammad A. Faramarzi ◽  
Somayeh Imanparast ◽  
Mohsen Amini
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Competitive Inhibition ◽  
Kinetic Studies ◽  
Developed Countries ◽  
Docking Studies ◽  
Antidiabetic Activity ◽  
Active Site Residues ◽  
Efficient Treatment ◽  
Enzyme Active Site

Background: Diabetes mellitus (DM) is an important global health problem especially in developed countries and insufficient lifestyle induces this phenomenon. Finding efficient treatment for DM is an interesting goal for researchers. Objective: Herein we tried to design and synthesize a series of quinazoline derivatives and investigate their bioactivity as possible α-Glucosidase inhibitor agents. Method: Compounds 1-14 were synthesized using a multicomponent reaction. 1HNMR, 13C NMR, MS, and IR spectroscopy were used for the characterization of synthesized compounds. α- Glucosidase inhibitory activity of compounds 1-14 was evaluated using p-nitrophenyl‐α‐Dglucopyranoside (pNPG) as a substrate of the α-glucosidase enzyme (EC3.2.1.20, Saccharomyces cerevisiae). The mechanism of inhibition of the α-glucosidase enzyme was investigated using kinetic studies. Molecular docking was also done using autodock software to find the possible mode of interaction of compound 8 and the enzyme active site. Results: Most of the tested compounds showed higher activity in inhibition of the enzyme in comparison to the standard, acarbose. Compound 8 exerted the best activity with the IC50 value of 291.5 μM. A kinetic study indicated a competitive inhibition of the α-glucosidase enzyme by compound 8. Finally, docking studies showed the interactions between compound 8 and enzyme active site residues. Conclusion: 2,4-Diarylquinazoline scaffold has good antidiabetic activity, so it is interesting to synthesize more 2,4-diarylquinazoline derivatives and evaluate their antidiabetic activities.

scholarly journals Pyrazolobenzothiazine-based carbothioamides as new structural leads for the inhibition of monoamine oxidases: design, synthesis, in vitro bioevaluation and molecular docking studies

MedChemComm ◽  
2017 ◽  
Vol 8 (2) ◽  
pp. 452-464 ◽  
Author(s):  
Syed Mobasher Ali Abid ◽  
Sana Aslam ◽  
Sumera Zaib ◽  
Syeda Mahwish Bakht ◽  
Matloob Ahmad ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Potent Inhibitor ◽  
Binding Mode ◽  
Docking Studies ◽  
Design Synthesis ◽  
Molecular Docking Studies ◽  
Monoamine Oxidases ◽  
Mao B

Binding mode of potent inhibitor (green) & cognate ligand (pink) in the active site of MAO-B.

scholarly journals Anti-tick effect and cholinesterase inhibition caused by Prosopis juliflora alkaloids: in vitro and in silico studies

2020 ◽  
Vol 29 (2) ◽  
Author(s):  
Hélimar Gonçalves de Lima ◽  
Francianne Oliveira Santos ◽  
Acidália Carine Vieira Santos ◽  
Gisele Dias da Silva ◽  
Rafaela Jesus dos Santos ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Active Site ◽  
Inhibitory Concentration ◽  
Interaction Mechanism ◽  
Docking Studies ◽  
Prosopis Juliflora ◽  
Cholinesterase Inhibition ◽  
In Silico Studies ◽  
Pi Interactions

Abstract We investigated the in vitro acaricide activity of the methanolic extract (ME) and alkaloid-rich fraction (AF) of Prosopis juliflora on Rhipicephalus microplus and correlated this effect with acetylcholinesterase (AChE) inhibition. The acaricide activity was evaluated using adult and larval immersion tests. Also, we studied the possible interaction mechanism of the major alkaloids present in this fraction via molecular docking at the active site of R. microplus AChE1 (RmAChE1). Higher reproductive inhibitory activity of the AF was recorded, with effective concentration (EC50) four times lower than that of the ME (31.6 versus 121 mg/mL). The AF caused mortality of tick larvae, with lethal concentration 50% (LC50) of 13.8 mg/mL. Both ME and AF were seen to have anticholinesterase activity on AChE of R. microplus larvae, while AF was more active with half-maximal inhibitory concentration (IC50) of 0.041 mg/mL. The LC-MS/MS analyses on the AF led to identification of three alkaloids: prosopine (1), juliprosinine (2) and juliprosopine (3). The molecular docking studies revealed that these alkaloids had interactions at the active site of the RmAChE1, mainly relating to hydrogen bonds and cation-pi interactions. We concluded that the alkaloids of P. juliflora showed acaricide activity on R. microplus and acted through an anticholinesterase mechanism.

scholarly journals PREDIKSI SENYAWA EUCALYPTUS SEBAGAI INHIBITOR POTENSIAL COVID-19 MAIN PROTEASE (Mpro) SECARA MOLECULAR DOCKING

2021 ◽  
Vol 6 (2) ◽  
pp. 77
Author(s):  
Muhammad Fauzi ◽  
Fauzi Rahman ◽  
Yulistia Budianti Soemari ◽  
Richa Purnamasari
Keyword(s):  
Free Energy ◽  
Molecular Docking ◽  
Active Site ◽  
Docking Studies ◽  
Therapeutic Drug ◽  
Free Energies ◽  
Virus Family ◽  
Main Protease ◽  
The World ◽  
Suitable Target

The development of cases infected with the COVID-19 virus in Indonesia continues to increase. COVID-19 is a member of the corona virus family that has spread throughout the world. The COVID-19 Main protease is considered a suitable target for drug design against SARS infection because it plays a role in the processing of polyproteins required for the reproduction of the coronavirus. Eucalyptus are claimed to be able to ward off the COVID-19 virus. Therefore it is necessary to evaluate the content of eucalyptus compounds against Main proteases by docking studies. Based on the results of research conducted using the active site on the Main protease, it is known that eucalyptus (-)-globulol, epiglobulol, and ledol compounds have free energies of -7.23 kcal/mol, -7.91 kcal/mol, and -7.39 kcal/mol, respectively. Remdesivir as a therapeutic drug for COVID-19 has a free energy of -7.67 kcal/mol. These three compounds bind to the amino acid Glu166 as remdisivir with the best binding affinity on the active site of the Main protease. So these three compounds have the potential to inhibit the COVID-19 virus.

Synthesis and Molecular Docking of New Thiophene Derivatives as Lactate Dehydrogenase-A Inhibitors

2019 ◽  
Vol 19 (10) ◽  
pp. 833-841 ◽  
Author(s):  
Abd El-Galil E. Amr ◽  
Mohamed F. El-Shehry ◽  
Alhussein A. Ibrahim ◽  
Hanaa M. Hosni ◽  
Mohamed A. Al-Omar ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Lactate Dehydrogenase ◽  
Glucose Metabolism ◽  
Cancer Cells ◽  
Active Site ◽  
Docking Studies ◽  
Reference Drug ◽  
Molecular Docking Studies ◽  
Thiophene Moiety ◽  
Thiophene Derivatives

Background & Objective: A series of novel derivatives possessing the thiophene moiety were synthesized using ethyl 5'-amino-2,3'-bithiophene-4'-carboxylate as the starting material. Methods: The new synthesized derivatives were screened as lactate dehydrogenase (LDH) inhibitors. LDH plays an important role in glucose metabolism in cancer cells and can affect tumor genesis and metastasis. Results: 3-Substituted p-tolylthieno[2,3-d]pyrimidin-4(3H)-ones 4 were the most potent inhibitors in this study compared to Galloflavin reference drug. Conclusion: Molecular docking studies on the Human Lactate Dehydrogenase active site were carried out on the synthesized compounds and the MolDock scores ranged between -127 to -171.

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