Synthesis, characterization, antitumor potential, BSA and DNA binding properties, and molecular docking study of some novel 3-hydroxy-3-pyrrolin-2-ones

Background: In order to make progress in discovering the new agents for cancer treatment with improved properties and considering the fact that 3-hydroxy-3-pyrrolin-2-ones belong to a class of biologically active compounds, we tested series of eleven novels 1,5-diaryl-4-(2-thienylcarbonyl)-3-hydroxy-3-pyrrolin-2-ones for their antitumor potential. Methods: All novel compounds were characterized by spectral (IR, NMR, MS) and elemental analysis. All novel 3-hydroxy-3-pyrrolin-2-ones were screened for their cytotoxic activity on two cancer cell lines, SW480 and MDA-MB 231, and non-transformed fibroblasts (MRC-5). Results: Compounds B8, B9, and B10 showed high cytotoxicity on SW480 cells together with good selectivity towards MRC-5 cells. It is important to empathize that the degree of selectivity of B8 and B10 was high (SI = 5.54 and 12.09, respectively). Besides, we explored the mechanisms of cytotoxicity of novel derivatives, B8, B9, and B10. The assay showed that tested derivatives induce an apoptotic type of cell death in SW480 cells, with a minor percent of necrotic cells. Additionally, to better understand the suitability of the compounds for potential use as anticancer medicaments, we studied their interactions with biomacromolecules (DNA or BSA). The results indicated that the tested compounds have a great affinity to displace EB from the EB-DNA complex through intercalation. Also, DNA and BSA molecular docking study was performed to predict the binding mode and the interaction region of the compounds. Conclusion: Achieved results indicate that our compounds have the potential to become candidates for use as medicaments.

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Molecular Docking Study of the Potential Relevance of the Natural Compounds Isoflavone and Myricetin to COVID-19

International Journal Bioautomation ◽

10.7546/ijba.2021.25.3.000796 ◽

2021 ◽

Vol 25 (3) ◽

pp. 271-282

Author(s):

Didik Priyandoko ◽

◽

Wahyu Widowati ◽

Mawar Subangkit ◽

Diana Jasaputra ◽

...

Keyword(s):

Molecular Docking ◽

Severe Acute Respiratory Syndrome ◽

Active Sites ◽

Docking Study ◽

Binding Mode ◽

Molecular Docking Study ◽

Wuhan City ◽

The World ◽

Novel Coronavirus ◽

Proteins Interactions

The 2019 novel coronavirus (2019-nCoV) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly from its origin in Wuhan City, Hubei Province, China, to the rest of the world. The efficacy of herbal treatment in the control of contagious disease was demonstrated during the 2003 outbreak of severe acute respiratory syndrome (SARS). Natural compound used for this study were isoflavone and myricetin. Molecular docking was performed to analyze binding mode of the compounds towards 12 proteins related to COVID-19. The prediction shows that isoflavone and myricetin have moderate probability of antiviral activity. All of the docked compounds occupied the active sites of the proteins related to COVID-19. Based on QSAR and molecular docking, interactions were predicted with 10 out of 12 potential COVID-19 proteins for myricetin and with 9 out of 12 proteins interactions for isoflavone. A potential disease alleviating action is suggested for isoflavone and myricetin in the context of COVID-19 infection.

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Synthesis of Diabetic II Inhibitors Based on 2-mercaptobenzimidazole and their Molecular Docking Study

10.20944/preprints201911.0375.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Muhammad Taha ◽

Fazal Rahim ◽

Shawkat Hayat ◽

Manikandan Selvaraj ◽

Rai Khalid Farooq ◽

...

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Binding Mode ◽

Alpha Amylase ◽

Variable Degree ◽

Molecular Docking Study ◽

Standard Drug ◽

Ic50 Value ◽

Ic50 Values ◽

Inhibitory Potential

In the search of potent α-amylase inhibitors, we have synthesized seventeen derivatives of 2-mercaptobenzimidazole bearing sulfonamide (1-17) and evaluated for their α-amylase inhibitory potential. All compounds display a variable degree of α-amylase activity having IC50 values ranging between 0.90 ± 0.05 to 11.20 ± 0.30 µM when compared with the standard drug acarbose having IC50 value 1.70 ± 0.10 µM. Compound 1, 2, 11, 12 and 14 having IC50 values 1.40 ± 0.10, 1.30 ± 0.05, 0.90 ± 0.05, 1.60 ± 0.05 and 1.60 ± 0.10 µM respectively were found many folds better than the standard drug acarbose. The remaining analogs showed good inhibitory potentials. All the synthesized compounds were characterized by HREI-MS, 1H and 13C-NMR. Structure activity relationship (SAR) has been recognized for all newly synthesized analogs. Through molecular docking study, binding mode of active analogs with α-amylase enzyme was confirmed.

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Molecular Docking Study on Some Isonicotinoyl Hydrazide Derivatives as Potential Inhibitors of COVID-19

Letters in Applied NanoBioScience ◽

10.33263/lianbs93.12171224 ◽

2020 ◽

Vol 9 (3) ◽

pp. 1217-1224

Keyword(s):

Molecular Docking ◽

Active Sites ◽

Antiviral Agent ◽

Docking Study ◽

Biologically Active ◽

New Drugs ◽

Molecular Docking Study ◽

Docking Score ◽

Protease Enzyme ◽

Potential Inhibitors

Coronavirus (COVID-19) is more than a health disaster;it is the greatest challenge that the world confrontsnowadays. There is a race to slow the spread of this disease. Searching for an antiviral agent to stop COVID-19 is an essential demand since there is no approved drug for COVID-19 till now. Molecular docking is a powerful tool in predicting new drugs. In this study, Favpiravir (Avigan), Hydroxychloroquine, and a series of biologically active compounds derived from iso-nicotinoyl hydrazide have been chosen for molecular docking study. Molecular docking was carried out by theMolegro virtual docker program on proteaseenzyme of COVID-19.The results showed that all the studied molecules are located in the active sites of protease after molecular docking. The tested nicotinoyl hydrazide derivatives showed a higher ranking docking score than Favpiravir (Avigan). According to the docking score ranking rearrangement, Hydroxychloroquine comes the third, and Favpiravir comes the last among the tested compounds. N(2-iso-nicotinoyl hydrazine-carbonthioyl)benzamide(2) and the enol form of (E)-N-(1-phenylethylidene)-nicotinohydrazide(7) have shown the highest docking score (123.23 and -123.12 kcal/mol respectively) among the tested compounds. Ligands (2) and (7) are expected to be potential inhibitors of the main protease enzyme of coronavirus.

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Design, Synthesis, and Molecular Docking of Paracyclophanyl-Thiazole Hybrids as Novel CDK1 Inhibitors and Apoptosis Inducing Anti-Melanoma Agents

Molecules ◽

10.3390/molecules25235569 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5569

Author(s):

Ashraf A. Aly ◽

Stefan Bräse ◽

Alaa A. Hassan ◽

Nasr K. Mohamed ◽

Lamiaa E. Abd El-Haleem ◽

...

Keyword(s):

Molecular Docking ◽

Cell Line ◽

Docking Study ◽

Binding Mode ◽

Molecular Docking Study ◽

Design Synthesis ◽

Cyclin Dependent Kinases ◽

Cycle Arrest ◽

Relative Safety ◽

One Dose Assay

Three new series of paracyclophanyl-dihydronaphtho[2,3-d]thiazoles and paracyclophanyl-thiazolium bromides were designed, synthesized, and characterized by their spectroscopic data, along with X-ray analysis. One-dose assay results of anticancer activity indicated that 3a–e had the highest ability to inhibit the proliferation of different cancer cell lines. Moreover, the hybrids 3c–e were selected for five-dose analyses to demonstrate a broad spectrum of antitumor activity without apparent selectivity. Interestingly, series I compounds (Z)-N-substituted-4,9-dihydronaphtho[2,3-d]thiazol-3(2H)-yl)-4′-[2.2]paracyclophanylamide) that are carrying 1,4-dihydronaphthoquinone were more active as antiproliferative agents than their naphthalene-containing congeners (series II: substituted 2-(4′-[2.2]paracyclophanyl)hydrazinyl)-4-(naphth-2-yl)-thiazol-3-ium bromide hybrids) and (series III: 3-(4′-[2.2]paracyclophanyl)amido-2-(cyclopropylamino)-4-(naphth-2-yl)thiazol-3-ium bromide) toward the SK-MEL-5 melanoma cell line. Further antiproliferation investigations of 3c and 3e on the healthy, normal unaffected SK-MEL-5 cell line indicated their relative safety. Compound 3c showed an inhibition of eight isoforms of cyclin-dependent kinases (CDK); however, it exhibited the lowest IC50 of 54.8 nM on CDK1 in comparison to Dinaciclib as a reference. Additionally, compound 3c revealed a remarkable downregulation of phospho-Tyr15 with a level (7.45 pg/mL) close to the reference. 3c mainly showed cell cycle arrest in the pre-G1 and G2/M phases upon analysis of the SK-MEL-5 cell line. The sequential caspase-3 assay for 3c indicated a remarkable overexpression level. Finally, a molecular docking study was adopted to elucidate the binding mode and interactions of the target compounds with CDK1.

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Molecular docking study for evaluating the binding mode and interaction of 2, 4-disubstituted quiloline and its derivatives as potent anti-tubercular agents against Lipoate protein B (LipB)

Turkish Computational and Theoretical Chemistry ◽

10.33435/tcandtc.458615 ◽

2019 ◽

Vol 3 (1) ◽

pp. 17-24

Author(s):

Shola ELIJAH ◽

Sani UBA ◽

Adamu UZAIRU

Keyword(s):

Molecular Docking ◽

Docking Study ◽

Binding Mode ◽

Molecular Docking Study ◽

Protein B

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Synthesis, characterization, antioxidant activity of β-diketonates, and effects of coordination to copper(II) ion on their activity: DNA, BSA interactions and molecular docking study

Medicinal Chemistry ◽

10.2174/1573406415666191024102520 ◽

2019 ◽

Vol 15 ◽

Author(s):

Nenad Joksimović ◽

Jelena Petronijević ◽

Nenad Janković ◽

Marijana Kosanić ◽

Dušan Milivojević ◽

...

Keyword(s):

Antioxidant Activity ◽

Ascorbic Acid ◽

Molecular Docking ◽

Spectroscopic Method ◽

Radical Scavenging ◽

Reducing Power ◽

Docking Study ◽

Biologically Active ◽

Scavenging Activity ◽

Molecular Docking Study

Background: In order to make some progress in discovering the more effective way to eliminate ROS which cause the oxidative stress in organism in humans and bearing in mind the fact that ethyl-2-hydroxy-4-aryl(alkyl)-4-oxo-2-butenoates (β-diketonates) belong to a class of biologically active compounds, series of β-diketonates were synthesized, characterized, and tested to evaluate there antioxidant activity. Further, to investigate how coordination to copper(II) ion affects the activity of β-diketonates, appropriate complexes were synthesized and characterized. Methods: All complexes were characterized by UV-Vis, IR, and EPR spectroscopy, MS spectrometry, and elemental analysis. Fluorescence spectroscopic method was used for investigations of the interactions between biomacromolecules (DNA or BSA) and compound 2E. Viscosity measurements and molecular docking study were performed to confirm the mode of interactions between DNA and BSA and compound 2E. Results: Scavenging activity on DPPH radical revealed that compounds 2A, 2B, and 2E possess largest free radical scavenging, comparable to standard while results of superoxide anion scavenging activities of tested samples showed that maximum scavenging activity (IC50=168.92 µg/mL) was found for 2E, very similar to standard ascorbic acid, followed by 2B and 2G. Results of the interactions between biomacromolecules and 2E indicated that 2E has the affinity to displace EB from the EB-DNA complex through intercalation [Ksv = (3.7 ± 0.1) × 103 M-1], while Ka value obtained via titration of BSA with 2E [Ka = (4.2 ± 0.2) × 105 M-1], support the fact that the significant amount of the drug could be transported and distributed through the cells. Conclusions: All β-diketonates exhibited better scavenging activities than their corresponding copper complexes. Among all tested compounds, 2E gave the highest reducing power, even higher than standard ascorbic acid, while reducing power for compounds 2A and 2B was also good but lower than standard. DNA and BSA binding study for 2E showed that this compound has potential to be used as medicament.

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Molecular Docking Study on the Binding Mode of Cardioselective Phenoxyaminopropanol Blocker into β-adrenergic Receptor Subtypes

Acta Facultatis Pharmaceuticae Universitatis Comenianae ◽

10.2478/v10219-012-0024-6 ◽

2012 ◽

Vol 59 (2) ◽

pp. 44-53

Author(s):

M. Polakovičová ◽

R. Čižmáriková

Keyword(s):

Molecular Docking ◽

Adrenergic Receptor ◽

Docking Study ◽

Binding Pocket ◽

Binding Mode ◽

Receptor Subtypes ◽

Molecular Docking Study ◽

Subtype Selectivity ◽

Extracellular Region ◽

Selective Ligand

AbstractStructural understanding of subtype specific ligand-binding pocket variations and interactions of ligand with receptor may facilitate design of novel selective drugs. To gain insights into the subtype selectivity of β-blockers we performed flexible molecular docking study to analyze the interaction mode of cardioselective phenoxyaminopropanol blocker into the β1 and β2-adrenergic receptor. The binding site analysis reveals a strong identity between important amino acid residues and interactions with ligand in orthosteric catecholamine- binding pocket. The differences in the binding mode of selective ligand have been identified in the extracellular region of receptor subtypes.

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Synthesis, DFT Calculations, DNA Binding and Molecular Docking Studies on Biologically Active N-((3-(4-Methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl)methylene)naphthyl Derivatives

Asian Journal of Organic & Medicinal Chemistry ◽

10.14233/ajomc.2021.ajomc-p351 ◽

2021 ◽

Vol 6 (4) ◽

pp. 292-301

Author(s):

P.V. Sandhya ◽

K.S. Femina ◽

A.V. Pradeep

Keyword(s):

Molecular Docking ◽

Dna Binding ◽

Biological Activities ◽

Condensation Reaction ◽

Geometry Optimization ◽

Docking Study ◽

Biologically Active ◽

Molecular Docking Study ◽

Binding Interaction

The biologically active pyrazole clubbed imino naphthyl derivatives have been designed and synthesized from 1-phenyl-3-methoxy phenyl-1H-pyrazol-4-carboxaldehyde and substituted naphthyl amines via acid catalyzed condensation reaction. All the synthesized compounds were well characterized by different spectroscopic and mass spectral techniques. The in vitro antibacterial, antifungal and antituberculosis studies were carried out. The molecular docking study was also done with the software Arguslab 4.0.1. The studied compounds showed moderate to good biological activities both experimentally and theoretically. Geometry optimization, DNA binding interaction and FMO analysis were also investigated with the help of Gaussian 16 package at B3LYP/6-31G(d,p) level.

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