Design, Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Eugenol Esters as Leishmanicidal Agents

Coelho, Camila; Santos, Thiago dos; Freitas, Poliany G.; Nunes, Juliana Barbosa; Marques, Marcos José; Padovani, Camila G. D.; Júdice, Wagner Alves de Souza; Camps, Ihosvany; Silveira, Nelson José Freitas da; Carvalho, Diogo Teixeira; Veloso, Márcia Paranho

doi:10.21577/0103-5053.20170192

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…Molecular dynamics (MD) simulations were used to validate the structural stability and conformational flexibility of a protein-ligand complex [44] , [66] . MD simulations provide powerful tools for the prediction of each atomic movement of protein, ligands, and physics governing interatomic interactions over a specific time [67] . To validate the structural stability and conformational flexibility protein ligands complex generated from the molecular docking study were subjected to 250 (ns) nanoseconds of MD simulations [68] .…”

Section: Methodsmentioning

confidence: 99%

Spike protein recognizer receptor ACE2 targeted identification of potential natural antiviral drug candidates against SARS-CoV-2

Pokhrel

Bouback

Samad³

et al. 2021

International Journal of Biological Macromolecules

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Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered till now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals' inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a 3D structure-based-pharmacophore model (SBPM) has been developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based on their binding affinity (−7.5, −7.1, −7.1, and −7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.

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Section: Methodsmentioning

confidence: 99%

Spike protein recognizer receptor ACE2 targeted identification of potential natural antiviral drug candidates against SARS-CoV-2

Pokhrel

Bouback

Samad³

et al. 2021

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

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“…Molecular dynamics (MD) simulations was used to validate the structural stability and conformational exibility of a protein-ligand complex [41]. MD simulations provide powerful tools for the prediction of each atomic movement of protein, ligands, and physics governing interatomic interactions over a speci c time [63]. To validate the structural stability and conformational exibility protein ligands complex generated from the molecular docking study were subjected to 250 (ns) nanoseconds of MD simulations [64].…”

Section: Molecular Dynamics (Md) Simulationmentioning

confidence: 99%

Spike Protein Recognizer Receptor ACE2 Targeted Identification of Potential Natural Antiviral Drug Candidates Against SARS-CoV-2

Bouback

Samad

Nur

et al. 2021

Preprint

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Angiotensin-converting enzyme 2 (ACE2), also known as peptidyl-dipeptidase A, belongs to the dipeptidyl carboxydipeptidases family has emerged as a potential antiviral drug target against SARS-CoV-2. Most of the ACE2 inhibitors discovered until now are chemical synthesis; suffer from many limitations related to stability and adverse side effects. However, natural, and selective ACE2 inhibitors that possess strong stability and low side effects can be replaced instead of those chemicals’ inhibitors. To envisage structurally diverse natural entities as an ACE2 inhibitor with better efficacy, a structure-based-pharmacophore model (SBPM) was developed and validated by 20 known selective inhibitors with their correspondence 1166 decoy compounds. The validated SBPM has excellent goodness of hit score and good predictive ability, which has been appointed as a query model for further screening of 11,295 natural compounds. The resultant 23 hits compounds with pharmacophore fit score 75.31 to 78.81 were optimized using in-silico ADMET and molecular docking analysis. Four potential natural inhibitory molecules namely D-DOPA (Amb17613565), L-Saccharopine (Amb6600091), D-Phenylalanine (Amb3940754), and L-Mimosine (Amb21855906) have been selected based onbinding affinity (−7.5, −7.1, −7.1, and −7.0 kcal/mol), respectively. Moreover, 250 ns molecular dynamics (MD) simulations confirmed the structural stability of the ligands within the protein. Additionally, MM/GBSA approach also used to support the stability of molecules to the binding site of the protein that also confirm the stability of the selected four natural compounds. The virtual screening strategy used in this study demonstrated four natural compounds that can be utilized for designing a future class of potential natural ACE2 inhibitor that will block the spike (S) protein dependent entry of SARS-CoV-2 into the host cell.

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“…Bearing in mind the resistance to MTZ and its side effects, especially with higher doses, the control of blastocystosis constitutes a challenge. Investigation of the antiprotozoal activity of S. aromaticum essential oil against Leishmania by Coelho et al, [34] showed that eugenol component of S. aromaticum inhibits leishmanial cysteine proteases, which are vital in several aspects of protozoa life cycle [35] . Furthermore, a surface-located cysteine protease was shown to be involved in the pro-survival role of B. legumain subtype 7 [36] .…”

Section: S Aromaticum Essential Oil Inhibition Of Viabilitymentioning

confidence: 99%

Potent lethal effect of Syzygium aromaticum essential oil on Blastocystis spp.: An in vitro study

Eldin

Hayam²

2019

Parasitologists United Journal

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Blastocystis spp. are protozoan inhabiting the gastrointestinal tract, with an incidence usually reaching 5% in developed countries, exceeding 40% in individuals with chronic gastrointestinal illness, and can reach up 76% in developing countries [1,2]. Infection with Blastocystis spp. can be detected in stool samples of asymptomatic individuals or patients complaining of diarrhea [3]. However, as the data depend on methods used for diagnosis, blastocystosis is likely underestimated [4]. Currently, Blastocystis spp. are included in WHO water sanitation programs [5]. It has been linked to the increased risk of allergic skin manifestations [6] , and inflammatory bowel disease [1] ; recently, a relation between blastocystosis and development of irritable bowel syndrome was reported [7]. Colorectal carcinoma was also linked to blastocystosis [8] , as solubilized antigen of Blastocystis spp. was reported to promote the growth of human colorectal cancer cells [9]. Thus, therapy of blastocystosis is required to avoid or reduce the development of its possible complications. Lately, contradictory findings about the response of blastocystosis to MTZ treatment emerged, with efficacy rates ranging from 0% to 100% [10-12]. In this context, there is a need for new therapeutic agents against blastocystosis with high effectiveness and low toxicity. In recent times, the study of plants used by traditional medicine is a mean of alternative treatment, and several anti-parasitic properties of natural products have been identified [13]. Of those natural products is Syzygium aromaticum eugenol rich essential oil. Commonly known as clove, it is native to tropical America and Australia [14]. The oil extract has been widely investigated due to its availability and high essential-oil contents, and has long been considered to have medicinal properties [15] , including anti-bacterial [16] , anti-trypanosomal [17] , and antimalarial actions [18]. Islamuddin et al., [19] reported that S. aromaticum essential oil induced apoptosis in L. donovani promastigotes. Additionally, it was found to have anti-Giardia activity [20]. S. aromaticum essential oil medicinal actions were attributed to the major component 'eugenol', that constitutes 89% of the oil [21] .

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Design, Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Eugenol Esters as Leishmanicidal Agents

Cited by 5 publications

References 24 publications

Spike protein recognizer receptor ACE2 targeted identification of potential natural antiviral drug candidates against SARS-CoV-2

Spike protein recognizer receptor ACE2 targeted identification of potential natural antiviral drug candidates against SARS-CoV-2

Spike Protein Recognizer Receptor ACE2 Targeted Identification of Potential Natural Antiviral Drug Candidates Against SARS-CoV-2

Potent lethal effect of Syzygium aromaticum essential oil on Blastocystis spp.: An in vitro study

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