In Silico Molecular Docking and in Vitro Analysis of Eugenol as Free Radical Scavenger in Patients with Dengue Infection

Background: Infections caused by drug resistant microorganisms have been increasing worldwide thereby being one of the major causes of morbidity in the 21st century. Klebsiella pneumoniae is one such bacteria causing lung inflammation, lung injury and death. Emergence of hyper-virulent and drug resistant species such as ESBL and CRKP has made this microbe a serious and urgent threat. The pace of emergence of these species is outgrowing the development of novel drug and vaccine candidates thereby focusing on drug repurposing approach. Objective: 1. Homology Modelling of Thymidylate Synthase. 2. Verification of Modelled Structure. 3. Molecular Docking. 4. Molecular Dynamic Simulation of Docked Complex. 5. In vitro analysis of 5-FU activity against Klebsiella pneumonia. Method: The 3-D structure of Thymidylate Synthase was predicted using Swiss-Model server and validated by in silico approaches. - Determination protein-protein interactions using STRING database. - Molecular docking. - MD simulations of 5-FU with predicted structure of thymidylate synthase. - In vitro antimicrobial drug sensitivity assay at different concentrations. Result: Hydrogen bond was observed in Molecular Docking - Protein-ligand complex remains stable during simulation. - 5-FU shows antimicrobial activity against Klebsiella pneumonia during In vitro study. Conclusion: Both In silico as well as in vitro analysis have indicated that 5-FU can potentially be developed as an antimicrobial agent towards Klebsiella pneumonia

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In silico molecular docking and in vitro analysis of ethanolic extract Ocimum sanctum Linn.: Inhibitory and apoptotic effects against non-small cell lung cancer

Veterinary World ◽

10.14202/vetworld.2021.3175-3187 ◽

2021 ◽

pp. 3175-3187

Author(s):

Ulayatul Kustiati ◽

T. S. Dewi Ratih ◽

N. Dwi Aris Agung ◽

Dwi Liliek Kusindarta ◽

Hevi Wihadmadyatami

Keyword(s):

Lung Cancer ◽

In Silico ◽

Ethanolic Extract ◽

Small Cell ◽

Ocimum Sanctum ◽

Active Compounds ◽

Vitro Analysis ◽

In Silico Molecular Docking ◽

In Vitro Analysis

Background and Aim: Lung cancer, especially non-small cell lung cancer (NSCLC), has been identified as the leading cause of cancer deaths worldwide. The mortality rate from lung cancer has been estimated to be 18.4%. Until now, conventional treatments have not yielded optimal results, thus necessitating an investigation into the use of traditional herbal plants as potential candidates for its treatment. This study aimed to determine the inhibitory and apoptotic activity of the ethanolic extract from Ocimum sanctum Linn. (EEOS) by in silico molecular docking and through in vitro studies using NSCLC cells (A549 cell line). Materials and Methods: Dried simplicia of Ocimum sanctum was converted into EEOS using the maceration method. Spectrophotometry was then employed to analyze the EEOS compound. The known main active compounds were further analyzed for inhibitory and apoptotic effects on gene signaling using in silico molecular docking involving the downloading of active compounds from PubChem and target proteins from the Protein Data Bank; the active compounds and proteins were then prepared using the Discovery Studio software v. 19.0.0 and the PyRX 0.8 program, interacted with the HEX 8.0.0 program, and visualized with the Discovery Studio Visualizer v. 19.0. Finally, an in vitro analysis was performed using an antiproliferative-cytotoxic test (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay in the NSCLC A549 cell line). Results: The analysis revealed that the active compounds in the ethanolic extract were dominated by quercetin (flavonoids) (47.23% b/b) and eugenol (phenolic) (12.14% b/b). These active compounds interacted with the active sites (residual amino acids) of the αvβ3 integrin, α5β1 integrin, caspase-3, caspase-9, and vascular endothelial growth factor. Hydrogen bonds and Pi-cation and Pi-alkyl interactions were involved in the relationships between the active compounds and the active sites and thus may reveal an antioxidant property of the extract. Furthermore, in vitro analysis showed the inhibitory and antiproliferative effects of the EEOS against non-small cell cancer (A549). Conclusion: Taken together, our data showed the ability of EEOS as an inhibitor and apoptotic agent for lung cancer; however, further research is needed to determine the exact mechanism of EEOS as an herbal medication.

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The Antiviral and Antimalarial Drug Repurposing in Quest of Chemotherapeutics to Combat COVID-19 Utilizing Structure-Based Molecular Docking

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323999200824115536 ◽

2020 ◽

Vol 23 ◽

Author(s):

Sisir Nandi ◽

Mohit Kumar ◽

Mridula Saxena ◽

Anil Kumar Saxena

Keyword(s):

Molecular Docking ◽

In Silico ◽

Drug Repurposing ◽

Clinical Settings ◽

The Novel ◽

In Silico Docking ◽

Biochemical Mechanisms ◽

Novel Coronavirus ◽

In Silico Molecular Docking

Background: The novel coronavirus disease (COVID-19) is caused by a new strain (SARS-CoV-2) erupted in 2019. Nowadays, it is a great threat that claims uncountable lives worldwide. There is no specific chemotherapeutics developed yet to combat COVID-19. Therefore, scientists have been devoted in the quest of the medicine that can cure COVID- 19. Objective: Existing antivirals such as ASC09/ritonavir, lopinavir/ritonavir with or without umifenovir in combination with antimalarial chloroquine or hydroxychloroquine have been repurposed to fight the current coronavirus epidemic. But exact biochemical mechanisms of these drugs towards COVID-19 have not been discovered to date. Method: In-silico molecular docking can predict the mode of binding to sort out the existing chemotherapeutics having a potential affinity towards inhibition of the COVID-19 target. An attempt has been made in the present work to carry out docking analyses of 34 drugs including antivirals and antimalarials to explain explicitly the mode of interactions of these ligands towards the COVID-19protease target. Results: 13 compounds having good binding affinity have been predicted towards protease binding inhibition of COVID-19. Conclusion: Our in silico docking results have been confirmed by current reports from clinical settings through the citation of suitable experimental in vitro data available in the published literature.

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In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽

10.1186/s13099-021-00443-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Padikkamannil Abishad ◽

Pollumahanti Niveditha ◽

Varsha Unni ◽

Jess Vergis ◽

Nitin Vasantrao Kurkure ◽

...

Keyword(s):

Escherichia Coli ◽

Molecular Docking ◽

In Silico ◽

Docking Studies ◽

Antimicrobial Efficacy ◽

Drug Resistant ◽

Protein Motifs ◽

Phytochemical Compounds ◽

In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

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