Preliminary analysis of a neotropical plant extract antiviral potential against Chikungunya and Mayaro viruses

Chikungunya and Mayaro fevers are viral infectious diseases, without vaccine or treatment, that causes fever and arthralgia. Establishing novel antiviral tools capable of preventing or treating Chikungunya virus (CHIKV), and Mayaro virus (MAYV) infections are needed. The use of plant-based compounds that affect the replication cycles of these viruses has been proposed as a promising strategy. Chiococca alba (L.) Hitchc. is a neotropical plant used by Yucatec Mayas traditional healers, mainly, as antipyretic and antirheumatic. To evaluate the potential of C. alba methanolic extracts against CHIKV and MAYV through preliminary analysis in vitro and in silico . The cytotoxicity profile of two C. alba roots methanolic extracts in Vero cells was performed by lysosomal viability using the neutral red assay, and the antiviral potential was determined by plaque assay. We further assessed, through in silico computational predictions, the possible interactions between the active site of the nsP2 proteases of these viruses with some secondary metabolites present in C. alba extracts, identified by High-Performance Liquid Chromatography (HPLC). Our partial phytochemical analysis revealed the presence of flavonoids, and phenolic acids in the C. alba extracts. Our in vitro assays showed that both C. alba extracts inhibited more than 70% of CHIKV and MAYV activities at 60 µg/mL concentration. Based on our in silico computational predictions, the flavonoids naringin and vitexin showed the greatest affinity energies with the CHIKV and MAYV nsP2 proteases, revealing the great potential of these compounds as viral inhibitors. The findings described here indicates that C. alba extracts, or their secondary metabolites, as a potential source of novel antiviral compounds.

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In-silico Studies of Isolated Phytoalkaloid Against Lipoxygenase: Study Based on Possible Correlation

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180220125406 ◽

2018 ◽

Vol 21 (3) ◽

pp. 215-221

Author(s):

Haroon Khan ◽

Muhammad Zafar ◽

Helena Den-Haan ◽

Horacio Perez-Sanchez ◽

Mohammad Amjad Kamal

Keyword(s):

In Silico ◽

Docking Studies ◽

In Vivo Studies ◽

In Vitro Assays ◽

Chronic Obstructive ◽

Lipoxygenase Inhibitors ◽

Lipoxygenase Inhibition ◽

In Silico Studies

Aim and Objective: Lipoxygenase (LOX) enzymes play an important role in the pathophysiology of several inflammatory and allergic diseases including bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, rheumatoid arthritis and chronic obstructive pulmonary disease. Inhibitors of the LOX are believed to be an ideal approach in the treatment of diseases caused by its over-expression. In this regard, several synthetic and natural agents are under investigation worldwide. Alkaloids are the most thoroughly investigated class of natural compounds with outstanding past in clinically useful drugs. In this article, we have discussed various alkaloids of plant origin that have already shown lipoxygenase inhibition in-vitro with possible correlation in in silico studies. Materials and Methods: Molecular docking studies were performed using MOE (Molecular Operating Environment) software. Among the ten reported LOX alkaloids inhibitors, derived from plant, compounds 4, 2, 3 and 1 showed excellent docking scores and receptor sensitivity. Result and Conclusion: These compounds already exhibited in vitro lipoxygenase inhibition and the MOE results strongly correlated with the experimental results. On the basis of these in vitro assays and computer aided results, we suggest that these compounds need further detail in vivo studies and clinical trial for the discovery of new more effective and safe lipoxygenase inhibitors. In conclusion, these results might be useful in the design of new and potential lipoxygenase (LOX) inhibitors.

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Repurposing of auranofin against bacterial infections: An In silico and In vitro study

Current Computer - Aided Drug Design ◽

10.2174/1386207323666200717155640 ◽

2020 ◽

Vol 16 ◽

Author(s):

Nidhi Sharma ◽

Arti Singh ◽

Ruchika Sharma ◽

Anoop Kumar

Keyword(s):

Broad Spectrum ◽

In Silico ◽

Antibacterial Agent ◽

Bacterial Infections ◽

In Vitro Assays ◽

Infection Model ◽

Synergistic Activity ◽

Bacterial Strains ◽

Molecular Docking Study

Aim: The aim of the study was to find out the role of auranofin as a promising broad spectrum antibacterial agent. Methods: In-vitro assays (Percentage growth retardation, Bacterial growth kinetics, Biofilm formation assay) and In-silico study (Molegro virtual docker (MVD) version 6.0 and Molecular operating environment (MOE) version 2008.10 software). Results: The in vitro assays have shown that auranofin has good antibacterial activity against Gram positive and Gram negative bacterial strains. Further, auranofin has shown synergistic activity in combination with ampicillin against S. aureus and B. subtilis whereas in combination with neomycin has just shown additive effect against E. coli, P. aeruginosa and B. pumilus. In vivo results have revealed that auranofin alone and in combination with standard drugs significantly decreased the bioburden in zebrafish infection model as compared to control. The molecular docking study have shown good interaction of auranofin with penicillin binding protein (2Y2M), topoisomerase (3TTZ), UDP-3-O-[3- hydroxymyristoyl] N-acetylglucosaminedeacetylase (3UHM), cell adhesion protein (4QRK), β-lactamase (5CTN) and arylsulphatase (1HDH) enzyme as that of reference ligand which indicate multimodal mechanism of action of auranofin. Finally, MTT assay has shown non-cytotoxic effect of auranofin. Conclusion: In conclusion, auranofin in combination with existing antibiotics could be developed as a broad spectrum antibacterial agent; however, further studies are required to confirm its safety and efficacy. This study provides possibility of use of auranofin apart from its established therapeutic indication in combination with existing antibiotics to tackle the problem of resistance.

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Computational and In-Vitro Validation of Natural Molecules as Potential Acetylcholinesterase Inhibitors and Neuroprotective Agents

Current Alzheimer Research ◽

10.2174/1567205016666181212155147 ◽

2019 ◽

Vol 16 (2) ◽

pp. 116-127 ◽

Cited By ~ 2

Author(s):

Ashwani Kumar ◽

Vineet Mehta ◽

Utkarsh Raj ◽

Pritish Kumar Varadwaj ◽

Malairaman Udayabanu ◽

...

Keyword(s):

In Silico ◽

Hippocampal Neurons ◽

Symptomatic Relief ◽

In Vitro Assays ◽

Disease Modifying Drugs ◽

In Silico Docking ◽

Ache Inhibitors ◽

Significant Difference ◽

Disease Modifying

Background: Cholinesterase inhibitors are the first line of therapy for the management of Alzheimer’s disease (AD), however, it is now established that they provide only temporary and symptomatic relief, besides, having several inherited side-effects. Therefore, an alternative drug discovery method is used to identify new and safer ‘disease-modifying drugs’. Methods: Herein, we screened 646 small molecules of natural origin having reported pharmacological and functional values through in-silico docking studies to predict safer neuromodulatory molecules with potential to modulate acetylcholine metabolism. Further, the potential of the predicted molecules to inhibit acetylcholinesterase (AChE) activity and their ability to protect neurons from degeneration was determined through in-vitro assays. Results: Based on in-silico AChE interaction studies, we predicted quercetin, caffeine, ascorbic acid and gallic acid to be potential AChE inhibitors. We confirmed the AChE inhibitory potential of these molecules through in-vitro AChE inhibition assay and compared results with donepezil and begacestat. Herbal molecules significantly inhibited enzyme activity and inhibition for quercetin and caffeine did not show any significant difference from donepezil. Further, the tested molecules did not show any neurotoxicity against primary (E18) hippocampal neurons. We observed that quercetin and caffeine significantly improved neuronal survival and efficiently protected hippocampal neurons from HgCl2 induced neurodegeneration, which other molecules, including donepezil and begacestat, failed to do. Conclusion: Quercetin and caffeine have the potential as “disease-modifying drugs” and may find application in the management of neurological disorders such as AD.

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Phytochemical analysis, Antimicrobial, insecticidal and antiradical activity of Hydnocarpus pentandra (Buch.-Ham.) Oken

International Journal of Phytomedicine ◽

10.5138/09750185.2163 ◽

2017 ◽

Vol 9 (4) ◽

pp. 576

Author(s):

Prashith Kekuda TR ◽

Dunkana Negussa Kenie ◽

Chetan DM ◽

Raghavendra L Hallur

Keyword(s):

Leaf Extract ◽

Antiradical Activity ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Extraction Process ◽

In Vitro Assays ◽

Phytochemical Analysis ◽

Zone Of Inhibition ◽

Bioactive Agents

Objectives: The present study was conducted to evaluate antimicrobial, insecticidal and radical scavenging activity of leaf extract of Hydnocarpus pentandra (Buch.-Ham.) Oken belonging to the family Achariaceae.Methods: Extraction process of shade dried and powdered leaf was carried out by maceration technique. Extract was screened for phytochemicals by standard tests. Antibacterial and antifungal activity of leaf extract was determined by Agar well diffusion and Poisoned food technique respectively. Antiradical activity of leaf extract was evaluated by two in vitro assays namely 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis 3-ethylbenzothiazoline 6-sulfonate (ABTS) free radical scavenging assays. Insecticidal activity of leaf extract was determined against II instar and IV instar larvae of Aedes aegypti.Results: Preliminary phytochemical analysis showed the presence of alkaloids, flavonoids, tannins, saponins, glycosides, triterpenes and steroids in the leaf extract. Leaf extract exhibited marked inhibitory activity against Gram positive bacteria when compared to Gram negative bacteria. Bacillus cereus (zone of inhibition 1.86±0.05cm) and Escherichia coli (zone of inhibition 1.06±0.05cm) were inhibited to highest and least extent respectively. Extract was effective in inhibiting mycelial growth of seed-borne fungi. Among fungi, the susceptibility to extract was in the order: Curvularia sp. (53.64% inhibition) > Fusarium sp. (45.81% inhibition) > Alternaria sp. (35.08% inhibition). The extract exhibited concentration dependent larvicidal activity with marked activity being observed against II instar larvae (LC50 value 0.79mg/ml) when compared to IV instar larvae (LC50 value 1.37mg/ml). Leaf extract scavenged DPPH and ABTS radicals dose dependently with an IC50 value of 13.91µg/ml and 6.03µg/ml respectively.Conclusions: The plant is shown to be an important source of bioactive agents. The observed bioactivities could be attributed to the phytochemicals present in the leaf extract. Further studies on characterization and bioactivity determination of isolated components from leaf extract are to be carried out.

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Plant Products as Antimicrobial Agents

Clinical Microbiology Reviews ◽

10.1128/cmr.12.4.564 ◽

1999 ◽

Vol 12 (4) ◽

pp. 564-582 ◽

Cited By ~ 2975

Author(s):

Marjorie Murphy Cowan

Keyword(s):

Secondary Metabolites ◽

Antimicrobial Agents ◽

Antimicrobial Properties ◽

Traditional Healers ◽

In Vivo Studies ◽

Current Status ◽

The Public ◽

The Earth

SUMMARY The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

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[18F]Amylovis as a Potential PET Probe for β-Amyloid Plaque: Synthesis, In Silico, In vitro and In vivo Evaluations

Current Radiopharmaceuticals ◽

10.2174/1874471012666190102165053 ◽

2019 ◽

Vol 12 (1) ◽

pp. 58-71 ◽

Cited By ~ 2

Author(s):

Suchitil Rivera-Marrero ◽

Laura Fernández-Maza ◽

Samila León-Chaviano ◽

Marquiza Sablón-Carrazana ◽

Alberto Bencomo-Martínez ◽

...

Keyword(s):

In Silico ◽

Specific Activity ◽

Senile Plaques ◽

Coupling Reaction ◽

In Vitro Assays ◽

Mice Model ◽

Wild Mice ◽

In Silico Studies

Background: Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart ([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice. Methods: Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were carried out to obtain 5 and 18F-Amylovis. Protein/Aß plaques binding, biodistribution, PET/CT Imaging and immunohistochemical studies were conducted in healthy/transgenic mice. Results: The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5 should have affinity to the Aβ-peptide, mainly through π-π interactions. According to a dynamic simulation study the ligand-Aβ peptide complexes are stable in simulation-time (ΔG = -5.31 kcal/mol). [18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The [18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB). According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to Aβ plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with rapid uptake (7 %ID/g at 5 min) and good washout (0.11±0.03 %ID/g at 60 min). Comparative PET dynamic studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant high uptake in the mice model. Conclusion: The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a promissory PET imaging agent to detect the presence of Aβ senile plaques.

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Assessing the Perturbing Effects of Drugs on Lipid Bilayers Using Gramicidin Channel-Based In Silico and In Vitro Assays

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.0c00958 ◽

2020 ◽

Vol 63 (20) ◽

pp. 11809-11818

Author(s):

Delin Sun ◽

Thasin A. Peyear ◽

W. F. Drew Bennett ◽

Matthew Holcomb ◽

Stewart He ◽

...

Keyword(s):

Lipid Bilayers ◽

In Silico ◽

In Vitro Assays ◽

Gramicidin Channel

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Chemical characterization and in vitro biological activity of Cymbopogon citratus extracts against Haemonchus spp. and Trichostrongylus spp. nematodes from sheep

Parasitology ◽

10.1017/s0031182020001432 ◽

2020 ◽

Vol 147 (13) ◽

pp. 1559-1568

Author(s):

Letícia Oliveira da Rocha ◽

Gloria Cristina da Silva Lemos ◽

Ivo José Curcino Vieira ◽

Raimundo Braz-Filho ◽

Silvério de Paiva Freitas ◽

...

Keyword(s):

Biological Activity ◽

Chemical Characterization ◽

Gastrointestinal Nematodes ◽

The Body ◽

Intestinal Cells ◽

Phytochemical Analysis ◽

Cymbopogon Citratus ◽

Thin Sections ◽

Methanolic Extracts

AbstractMedicinal plants have been the focus of several studies due to their nematicide properties which can be used to control nematodes in sheep. No study has examined the morphological effects of Cymbopogon citratus on nematodes. Thus, this study evaluated the chemical composition, nematicidal activity and effects of C. citratus extracts on the morphology of eggs and infective larvae (L3) of sheep. Aqueous and methanolic extracts and fractions of C. citratus were obtained and analysed in vitro. The C. citratus extracts were effective against Haemonchus spp. and Trichostrongylus spp. larvae and eggs. Ten fractions were obtained from C. citratus, six of which had high ovicidal activity at 1000 μg mL−1, and two fractions had high activity at all tested concentrations. The phytochemical analysis identified the presence of compounds such as terpenoids, various ketones, esters, and fatty acids. The ultrastructural analysis showed deformations of the cuticle and wilting along the body of the nematodes at all concentrations. The muscular layer, intestinal cells and the mitochondria profile showed damage compared to the typical pattern. Ultra-thin sections of eggs treated with methanolic fractions of C. citratus presented modifications. This study showed the biological activity and effects of C. citratus on the gastrointestinal nematodes in sheep.

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Chemical synthesis and characterization of a new quinazolinedione competitive antagonist for strigolactone receptors with an unexpected binding mode

Biochemical Journal ◽

10.1042/bcj20190288 ◽

2019 ◽

Vol 476 (12) ◽

pp. 1843-1856 ◽

Cited By ~ 1

Author(s):

Cyril Hamiaux ◽

Lesley Larsen ◽

Hui Wen Lee ◽

Zhiwei Luo ◽

Prachi Sharma ◽

...

Keyword(s):

In Silico ◽

Binding Mode ◽

Crystal Structure Analysis ◽

Tolfenamic Acid ◽

In Vitro Assays ◽

Inhibition Mechanism ◽

In Planta ◽

Competitive Antagonist ◽

In Silico Docking

Abstract Strigolactones (SLs) are multifunctional plant hormones regulating essential physiological processes affecting growth and development. In vascular plants, SLs are recognized by α/β hydrolase-fold proteins from the D14/DAD2 (Dwarf14/Decreased Apical Dominance 2) family in the initial step of the signaling pathway. We have previously discovered that N-phenylanthranilic acid derivatives (e.g. tolfenamic acid) are potent antagonists of SL receptors, prompting us to design quinazolinone and quinazolinedione derivatives (QADs and QADDs, respectively) as second-generation antagonists. Initial in silico docking studies suggested that these compounds would bind to DAD2, the petunia SL receptor, with higher affinity than the first-generation compounds. However, only one of the QADs/QADDs tested in in vitro assays acted as a competitive antagonist of SL receptors, with reduced affinity and potency compared with its N-phenylanthranilic acid ‘parent’. X-ray crystal structure analysis revealed that the binding mode of the active QADD inside DAD2's cavity was not that predicted in silico, highlighting a novel inhibition mechanism for SL receptors. Despite a ∼10-fold difference in potency in vitro, the QADD and tolfenamic acid had comparable activity in planta, suggesting that the QADD compensates for lower potency with increased bioavailability. Altogether, our results establish this QADD as a novel lead compound towards the development of potent and bioavailable antagonists of SL receptors.

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IN VITRO ANTI-INFLAMMATORY AND CYTOTOXICITY OF CRINUM X AMABILE GROWN IN ECUADOR

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i10.26962 ◽

2018 ◽

Vol 11 (10) ◽

pp. 99

Author(s):

Vinueza Diego ◽

Portero Santiago ◽

Pilco Gisela ◽

GarcÍa Marlene ◽

Acosta Karen ◽

...

Keyword(s):

Total Alkaloid ◽

Inflammatory Activity ◽

Tetrazolium Salt ◽

Phytochemical Analysis ◽

Total Alkaloids ◽

Methanolic Extracts ◽

Anti Inflammatory ◽

Alkaloid Extracts ◽

Phytochemical Studies

Objective: The aim of this research was to assess the in vitro anti-inflammatory activity and cytotoxicity of the methanolic extract and total alkaloid extract obtained from leaves and bulbs of Crinum x amabile (CA) growing in Ecuador.Methods: Methanolic extracts of dry powered leaves and bulbs of CA obtained by cold maceration method were subjected to preliminary phytochemical screening. Total alkaloid extracts of leaves and bulbs of CA were obtained by conventional extraction of alkaloids base with an organic solvent. Furthermore, the anti-inflammatory activity and cytotoxicity of the four extracts were investigated by in vitro isolated neutrophils model using stable tetrazolium salt (WST-1).Results: Phytochemical analysis of methanolic extracts revealed the major classes of phytochemicals such as alkaloids, flavonoids, tannins, triterpenes, and steroids, but no proteins or saponins could be detected on leaves extract. Extracts obtained from bulbs both methanolic and total alkaloids of CA show an interesting anti-inflammatory activity, although it was not significant compared to the standard anti-inflammatory drug, aspirin. Cytotoxicity of bulb alkaloid extract was lower compared with all of the other extracts.Conclusion: Based on the results of this research, it could be concluded that CA is a very interesting source of natural anti-inflammatory compounds (especially alkaloids) which could be used to prevent many chronic disorders. Further, phytochemical studies are necessary to identify the chemical compounds responsible for the significant anti-inflammatory activity showed.

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