scholarly journals Natural and Semisynthetic Triterpenes from Combretum leprosum Mart. with Antiplasmodial Activity

2022 ◽  
Author(s):  
Guilherme Passarini ◽  
Amália Ferreira ◽  
Leandro Moreira-Dill ◽  
Fernando Zanchi ◽  
Aurileya de Jesus ◽  
...  
Keyword(s):  
Artemisinin Combination Therapy ◽  
In Silico Analysis ◽  
Vero Cells ◽  
Enoyl Reductase ◽  
First Choice ◽  
Diphenyltetrazolium Bromide ◽  
Combretum Leprosum ◽  
Resistant Strains ◽  
Green Technique

Malaria is responsible for thousands of deaths each year. Currently, artemisinin combination therapy (ACT) is used as first-choice medication against the disease. However, the emergence of resistant strains prompts the search for alternative compounds. The present study aimed to investigate the antiplasmodial activities of natural triterpenes (compounds 1 and 2), and semisynthetic derivatives 1a, 1b, 1c, and 1d. Antiplasmodial assays were carried out using the SYBR Green technique, whereas cytotoxicity was evaluated by the MTT (3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide) method. Hemolytic assays were performed on human erythrocytes. An in silico analysis of the compounds against PfENR (Plasmodium falciparum 2-trans-enoyl-reductase) was carried out by molecular docking. Experiments with 1, and its derivatives against P. falciparum showed that 1a was very similar in terms of biological activity to compound 1 (half maximal inhibitory concentration (IC50) ca. 4 μM), whereas 1b, 1c, and 1d had reduced antiplasmodial activities (IC50 between 8-103 μM). The selectivity indexes of 1 and 1d for HepG2, and Vero cells were > 10. Docking results partially agreed with the in vitro experiments, with 1 and 1c having the best and worst affinities with PfENR, respectively. In conclusion, the results showed that 1 and 1d may serve as biotechnological tools in the development of antimalarial drugs.

scholarly journals In vitro cytotoxicity of Aspilia pluriseta Schweinf. extract fractions

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Sospeter N. Njeru ◽  
Jackson M. Muema
Keyword(s):  
Biological Activities ◽  
Vero Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extract ◽  
Lack Of Information ◽  
Information Gap ◽  
Diphenyltetrazolium Bromide ◽  
Potential Use

Abstract Objectives We and others have shown that Aspilia pluriseta is associated with various biological activities. However, there is a lack of information on its cytotoxicity. This has created an information gap about the safety of A. pluriseta extracts. As an extension to our recent publication on the antimicrobial activity and the phytochemical characterization of A. pluriseta root extracts, here we report on cytotoxicity of tested solvent fractions. We evaluated the potential cytotoxicity of these root extract fractions on Vero cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results We show that all solvent extract fractions (except methanolic solvent fractions) had cytotoxic concentration values that killed 50% of the Vero cells (CC50) greater than 20 µg/mL and selectivity index (SI) greater than 1.0. Taken together, we demonstrate that, A. pluriseta extract fractions’ earlier reported bioactivities are within the acceptable cytotoxicity and selective index limits. This finding scientifically validates the potential use of A. pluriseta in the discovery of safe therapeutics agents.

scholarly journals IN VITRO ANTIPLASMODIAL ACTIVITY OF FLOWER EXTRACTS FROM COMBRETUM LEPROSUM MART (MOFUMBO)

2016 ◽  
Vol 39 (1) ◽  
pp. 84 ◽  
Author(s):  
Guilherme Matos Passarini ◽  
Daniel Sol Medeiros ◽  
Dionatas Ulisses de Oliveira Meneguetti ◽  
Renato Abreu Lima ◽  
Valdir Alves Facundo ◽  
...  
Keyword(s):  
At Risk ◽  
Silica Gel ◽  
Column Chromatography ◽  
Chloroform Extract ◽  
Antiplasmodial Activity ◽  
Pharmacological Studies ◽  
Combretum Leprosum ◽  
Resistant Strains ◽  
Active Substances

Malaria is the cause of hundreds of deaths per year , besides putting billions of people at risk of developing disease. When it comes to its therapy, the drugs used currently are losing its efficacy due to increase inn the frequency of resistant strains of the parasite, highlight the importance for the serach of new classes of molecules prsentign antiplasmodial activity. In the present work, the antiplasmodial activities of five extracts from the flowers of Comretum leprosum are described. The method employed for obtaingine the extracts was silica gel column chromatography, and the techniques used for the analysis of antiplasmodial activity and citotoxicity were ELISA and MTT respectively, were a selectivitu index was calculated after the obtainign of these two values. The extract presenting the highest antiplasmodial activity was the chloroform extract, however, this extrac also presented the higther cytotoxicity and therefore the extract presenting the best overall activity was the hexane extract. The study deminstrated the plant Combretum leprosum has active substances against P. falciparum and therefore is a potential to be expored in funther pharmacological studies.

SARS-CoV-2 proteins bind heme and hemoglobin

2021 ◽  
Author(s):  
Salvatore Giovanni De-Simone ◽  
Guilherme Curty Lechuga ◽  
Franklin Souza-Silva ◽  
Carolina de Queiroz Sacramento ◽  
Monique Ramos de Oliveira Trugilho ◽  
...  
Keyword(s):  
Viral Replication ◽  
Protein Interactions ◽  
Protoporphyrin Ix ◽  
In Silico Analysis ◽  
Viral Proteins ◽  
Vero Cells ◽  
Host Cells ◽  
Respiratory Syndrome Virus ◽  
Primary Concern

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2), has led to a global crisis that included collapsing healthcare systems and shut-down communities, producing considerable economic burden. Despite the number of effective vaccines quickly implemented, the emergence of new variants is a primary concern. The scientific community undertook a rapid response to better study this new virus. However, critical questions about viral protein-protein interactions and mechanisms of its physiopathology are still unclear. Although severe COVID-19 was associated with hematological dysfunctions, scarce experimental data were produced about iron dysmetabolism and the viral proteins’ possible interaction with hemoglobin (Hb) chains. This work demonstrates the binding of SARS-CoV-2 proteins to hemin and Hb using a multimethodological approach. In silico analysis indicated binding motifs between a cavity in the viral nucleoprotein and hemoglobin’s porphyrin coordination region. Different hemin binding capacities of mock and SARS-CoV-2-infected culture extracts were noticed using gel electrophoresis and TMB staining. Hemin-binding proteins were isolated from SARS-CoV-2-infected cells by affinity chromatography and identified by shotgun proteomics, indicating that structural (nucleoprotein, spike, and membrane protein) and non-structural (Nsp3 and Nsp7) viral proteins interact with hemin. In vitro analyses of virus adsorption to host cells and viral replication studies in Vero cells demonstrated inhibitory activities - at different levels - by hemin, protoporphyrin IX (PpIX) Hb. Strikingly, free Hb at 1mM suppressed viral replication (99 %), and its interaction with SARS-CoV-2 was localized to the RBD region of the Spike protein. The findings showed clear evidence of new avenues to disrupt viral replication and understand virus physiopathology that warrants further investigation.

scholarly journals Anti-Herpetic, Anti-Dengue and Antineoplastic Activities of Simple and Heterocycle-Fused Derivatives of Terpenyl-1,4-Naphthoquinone and 1,4-Anthraquinone

Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1279 ◽  
Author(s):  
Vicky Roa-Linares ◽  
Yaneth Miranda-Brand ◽  
Verónica Tangarife-Castaño ◽  
Rodrigo Ochoa ◽  
Pablo García ◽  
...  
Keyword(s):  
Anticancer Agents ◽  
Higher Plants ◽  
Biological Activities ◽  
Human Herpesvirus ◽  
In Silico Analysis ◽  
Vero Cells ◽  
Antiviral Compound ◽  
Viral Attachment ◽  
Virus Serotype

Quinones are secondary metabolites of higher plants associated with many biological activities, including antiviral effects and cytotoxicity. In this study, the anti-herpetic and anti-dengue evaluation of 27 terpenyl-1,4-naphthoquinone (NQ), 1,4-anthraquinone (AQ) and heterocycle-fused quinone (HetQ) derivatives was done in vitro against Human Herpesvirus (HHV) type 1 and 2, and Dengue virus serotype 2 (DENV-2). The cytotoxicity on HeLa and Jurkat tumor cell lines was also tested. Using plaque forming unit assays, cell viability assays and molecular docking, we found that NQ 4 was the best antiviral compound, while AQ 11 was the most active and selective molecule on the tested tumor cells. NQ 4 showed a fair antiviral activity against Herpesviruses (EC50: <0.4 µg/mL, <1.28 µM) and DENV-2 (1.6 µg/mL, 5.1 µM) on pre-infective stages. Additionally, NQ 4 disrupted the viral attachment of HHV-1 to Vero cells (EC50: 0.12 µg/mL, 0.38 µM) with a very high selectivity index (SI = 1728). The in silico analysis predicted that this quinone could bind to the prefusion form of the E glycoprotein of DENV-2. These findings demonstrate that NQ 4 is a potent and highly selective antiviral compound, while suggesting its ability to prevent Herpes and Dengue infections. Additionally, AQ 11 can be considered of interest as a leader for the design of new anticancer agents.

scholarly journals In Vitro Cytotoxicity of Aspilia Pluriseta Schweinf. Extract Fractions

2020 ◽  
Author(s):  
Sospeter Ngoci Njeru ◽  
Jackson Mbithi Muema
Keyword(s):  
Biological Activities ◽  
Vero Cells ◽  
In Vitro Cytotoxicity ◽  
Root Extracts ◽  
Lack Of Information ◽  
Information Gap ◽  
Diphenyltetrazolium Bromide ◽  
Potential Use

Abstract Objectives: We and others have shown that Aspilia pluriseta is associated with various biological activities. However, there is a lack of information on A. pluriseta cytotoxicity. This has created an information gap about the safety of A. pluriseta extracts. As an extension to our recent publication on the antimicrobial activity and the phytochemicals characterization of A. pluriseta root extracts, here we report the missing data on cytotoxicity of tested extracts. We evaluated the potential cytotoxicity of the root extracts on Vero cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: We show that all solvent extracts (except methanolic solvent fractions) had cytotoxic concentration values that killed 50% of the Vero cells (CC50) greater than 20 µg/mL and selectivity index (SI) of greater than 1.0. Taken together, we demonstrate that, A. pluriseta extract fractions’ earlier reported bioactivity are within the acceptable cytotoxicity and selective index limits. This scientifically validates the potential use of A. pluriseta in the discovery of safe therapeutics agents.

scholarly journals In Vitro Activity of Pentamidine Isethionate against Trophozoite and Cyst of Acanthamoeba

2021 ◽  
Author(s):  
Massoud Behnia ◽  
Alireza Latifi ◽  
Mostafa Rezaian ◽  
Sharmin Kharazi ◽  
Mehdi Mohebali ◽  
...  
Keyword(s):  
Mtt Assay ◽  
Vero Cells ◽  
Acanthamoeba Keratitis ◽  
Inhibitory Effect ◽  
Blue Staining ◽  
Medical Sciences ◽  
Diphenyltetrazolium Bromide ◽  
Pentamidine Isethionate ◽  
Ic50 Values

Background: Acanthamoebae are a causative agent of Acanthamoeba keratitis (AK) in immunocompetent individuals. Since access to propamidine isethionate (Brolene®) as a first-line treatment has been limited in recent years, in the current study, we examined the effects of pentamidine isethionate against trophozoite and cyst forms of Acanthamoeba. Methods: This experimental study was conducted in the Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran, during 2019-2020. Pentamidine isethionate at concentrations of 50, 100, 200, 400, 600, 800, and 1000 µM were tested against trophozoites and cyst stages of T4 genotype, at 24- and 48-hour incubation period, and the viability was determined by trypan blue staining. In addition, the cytotoxic effect of the drug was examined in Vero cells using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: The 50% inhibitory concentration (IC50) of pentamidine isethionate on trophozoite after 24 and 48h were 97.4 µM and 60.99 µM. These results on cyst after 24 and 48h were 470 µM and 175.5 µM, respectively. In MTT assay, the drug showed an inhibitory effect on Vero cell growth with IC50 values of 115.4 µM and 87.42 µM after 24h and 48h, respectively. Conclusion: Pentamidine isethionate exhibited an inhibitory effect on trophozoite and cyst. Given that the trophozoicidal activity of the drug is in the safe dose, it could be suggested as an alternative in patients with AK; however, further investigation is needed in an animal model to confirm the data.

scholarly journals Nanoemulsions of Green Tea Catechins and Other Natural Compounds for the Treatment of Urinary Tract Infection: Antibacterial Analysis

2019 ◽  
Vol 9 (3) ◽  
pp. 401-408
Author(s):  
Atinderpal Kaur ◽  
Reema Gabrani ◽  
Shweta Dang
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Biofilm Formation ◽  
Vero Cells ◽  
Bacterial Strains ◽  
Diphenyltetrazolium Bromide ◽  
Bacterial Action ◽  
Resistant Strains ◽  
Antibacterial Potential

Purpose: Nanoemulsions (NEs) of polyphenon 60 (P60) and cranberry (NE I) and P60 and curcumin (NE II) were prepared with the aim to enhance anti-bacterial potential and to understand the mechanism of anti-bacterial action of the encapsulated compounds. Methods: To evaluate the antibacterial potential of the developed NE, microtiter biofilm formation assay was performed. The cytotoxicity analysis was done to assess the toxicity profile of the NEs. Further antibacterial analysis against uropathogenic strains was performed to check the developed NEs were effective against these strains. Results: In microtiter dish biofilm formation assay, both NE formulations inhibited the growth more effectively (Av. % inhibition ~84%) as compared to corresponding aqueous solution (Av. % inhibition ~64%) and placebo (Av. % inhibition ~59%) at their respective minimum inhibitory concentration (MIC) values. Cytotoxicity analysis using 3-(4,5-Dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT assay) showed that the formulations were nontoxic to Vero cells. The antibacterial studies against uropathogenic resistant strains also showed that NEs effectively inhibited the growth of bacterial strains. Conclusion: From different studies it was concluded that both the NE’s were able to inhibit bacterial strains and could be further used for the treatment of urinary tract infection (UTI). The antibacterial activity of developed NEs showed that these could be used as alternative therapies for the treatment of UTI.

scholarly journals IN VITRO ANTIPLASMODIAL AND CYTOTOXIC ACTIVITIES OF A SUNGKAI (PERONEMA CANESCENS) LEAF EXTRACT

2018 ◽  
Vol 10 (10) ◽  
pp. 109
Author(s):  
Jhons Fatriyadi Suwandi ◽  
Mahardika Agus Wijayanti ◽  
Mustofa .
Keyword(s):  
Plasmodium Falciparum ◽  
Vero Cells ◽  
In Vitro Cytotoxicity ◽  
Selectivity Index ◽  
Antiplasmodial Activity ◽  
Cytotoxic Activities ◽  
Aqueous Extracts ◽  
Diphenyltetrazolium Bromide ◽  
Ic50 Values

Objective: The aim of this study was to assess the antiplasmodial and cytotoxic activities and to evaluate the selectivity indices of acetone, ethanol and aqueous extracts of Peronema canescens leaves.Methods: Antiplasmodial activity was measured in vitro against Plasmodium falciparum strains D10 and FCR3 by 72 h incubation at 37 °C in a candle jar. Parasitaemia was calculated by counting the parasite numbers in thin smears. In vitro cytotoxicity was assayed in Vero cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and reading the absorbency at 595 nm with an ELISA reader. The assessed parameters included: 50% inhibitory concentration (IC50) of antiplasmodial activity, IC50 of cytotoxic activity and the selectivity index of the Peronema canescens leaf extract.Results: The IC50 values for the acetone, ethanol and aqueous extracts were 26.33±1.65, 37.96±8.17 and 12.26±1.05 μg/ml, respectively, against the Plasmodium falciparum D10 strain and 51.14±8.65, 70.22±14.13 and 34.85±6.04 μg/ml, respectively, against the FCR3 strain. For Vero cells, the IC50 values for the acetone, ethanol and aqueous extracts were 23.37±5.63, 629.46±24.85 and 634.00±144.82 μg/ml, respectively. The selectivity indices of these extracts were 0.89, 16.46 and 51.70, respectively, for the D10 strain and 0.46, 8.90 and 18.00, respectively, for the FCR3 strain.Conclusion: The aqueous extract of Peronema canescens leaves had the highest in vitro antiplasmodial activity and the best selectivity index.

Mechanisms involved in effects of antimicrobial peptides, bactenectins ChBac3.4, ChBac5, and mini-ChBac7.5Nb, on bacterial cells

2017 ◽  
pp. 43-50
Author(s):  
О.В. Шамова ◽  
М.С. Жаркова ◽  
П.М. Копейкин ◽  
Д.С. Орлов ◽  
Е.А. Корнева
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Innate Immunity ◽  
Infectious Diseases ◽  
Metabolic Activity ◽  
Capra Hircus ◽  
Bacterial Cells ◽  
Antibiotic Resistant ◽  
Resistant Strains

Антимикробные пептиды (АМП) системы врожденного иммунитета - соединения, играющие важную роль в патогенезе инфекционных заболеваний, так как обладают свойством инактивировать широкий спектр патогенных бактерий, обеспечивая противомикробную защиту живых организмов. В настоящее время АМП рассматриваются как потенциальные соединения-корректоры инфекционной патологии, вызываемой антибиотикорезистентными бактериями (АБР). Цель данной работы состояла в изученим механизмов антибактериального действия трех пептидов, принадлежащих к семейству бактенецинов - ChBac3.4, ChBac5 и mini-ChBac7.5Nb. Эти химически синтезированные пептиды являются аналогами природных пролин-богатых АМП, обнаруженных в лейкоцитах домашней козы Capra hircus и проявляющих высокую антимикробную активность, в том числе и в отношении грамотрицательных АБР. Методы. Минимальные ингибирующие и минимальные бактерицидные концентрации пептидов (МИК и МБК) определяли методом серийных разведений в жидкой питательной среде с последующим высевом на плотную питательную среду. Эффекты пептидов на проницаемость цитоплазматической мембраны бактерий для хромогенного маркера исследовали с использованием генетически модифицированного штамма Escherichia coli ML35p. Действие бактенецинов на метаболическую активность бактерий изучали с применением маркера резазурина. Результаты. Показано, что все исследованные пептиды проявляют высокую антимикробную активность в отношении Escherichia coli ML35p и антибиотикоустойчивых штаммов Escherichia coli ESBL и Acinetobacter baumannii in vitro, но их действие на бактериальные клетки разное. Использован комплекс методик, позволяющих наблюдать в режиме реального времени динамику действия бактенецинов в различных концентрациях (включая их МИК и МБК) на барьерную функцию цитоплазматической мембраны и на интенсивность метаболизма бактериальных клеток, что дало возможность выявить различия в характере воздействия бактенецинов, отличающихся по структуре молекулы, на исследуемые микроорганизмы. Установлено, что действие каждого из трех исследованных бактенецинов в бактерицидных концентрациях отличается по эффективности нарушения целостности бактериальных мембран и в скорости подавления метаболизма клеток. Заключение. Полученная информация дополнит существующие фундаментальные представления о механизмах действия пролин-богатых пептидов врожденного иммунитета, а также послужит основой для биотехнологических исследований, направленных на разработку на базе этих соединений новых антибиотических препаратов для коррекции инфекционных заболеваний, вызываемых АБР и являющимися причинами тяжелых внутрибольничных инфекций. Antimicrobial peptides (AMPs) of the innate immunity are compounds that play an important role in pathogenesis of infectious diseases due to their ability to inactivate a broad array of pathogenic bacteria, thereby providing anti-microbial host defense. AMPs are currently considered promising compounds for treatment of infectious diseases caused by antibiotic-resistant bacteria. The aim of this study was to investigate molecular mechanisms of the antibacterial action of three peptides from the bactenecin family, ChBac3.4, ChBac5, and mini-ChBac7.5Nb. These chemically synthesized peptides are analogues of natural proline-rich AMPs previously discovered by the authors of the present study in leukocytes of the domestic goat, Capra hircus. These peptides exhibit a high antimicrobial activity, in particular, against antibiotic-resistant gram-negative bacteria. Methods. Minimum inhibitory and minimum bactericidal concentrations of the peptides (MIC and MBC) were determined using the broth microdilution assay followed by subculturing on agar plates. Effects of the AMPs on bacterial cytoplasmic membrane permeability for a chromogenic marker were explored using a genetically modified strain, Escherichia coli ML35p. The effect of bactenecins on bacterial metabolic activity was studied using a resazurin marker. Results. All the studied peptides showed a high in vitro antimicrobial activity against Escherichia coli ML35p and antibiotic-resistant strains, Escherichia coli ESBL and Acinetobacter baumannii, but differed in features of their action on bacterial cells. The used combination of techniques allowed the real-time monitoring of effects of bactenecin at different concentrations (including their MIC and MBC) on the cell membrane barrier function and metabolic activity of bacteria. The differences in effects of these three structurally different bactenecins on the studied microorganisms implied that these peptides at bactericidal concentrations differed in their capability for disintegrating bacterial cell membranes and rate of inhibiting bacterial metabolism. Conclusion. The obtained information will supplement the existing basic concepts on mechanisms involved in effects of proline-rich peptides of the innate immunity. This information will also stimulate biotechnological research aimed at development of new antibiotics for treatment of infectious diseases, such as severe in-hospital infections, caused by antibiotic-resistant strains.

Formulation and Evaluation of Mefloquine Hydrochloride Nanoparticles

2014 ◽  
Vol 7 (1) ◽  
pp. 2377-2386
Author(s):  
Dilip Kumar Gupta ◽  
B K Razdan ◽  
Meenakshi Bajpai
Keyword(s):  
Particle Size ◽  
Sustained Release ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Taste Masking ◽  
Diffusion Method ◽  
Drug Entrapment Efficiency ◽  
Resistant Strains ◽  
Vitro Release

The present study deals with the formulation and evaluation of mefloquine hydrochloride nanoparticles. Mefloquine is a blood schizonticidal quinoline compound, which is indicated for the treatment of mild-to-moderate acute malarial infections caused by mefloquine-susceptible multi-resistant strains of P. falciparum and P. vivax. The purpose of the present work is to minimize the dosing frequency, taste masking toxicity and to improve the therapeutic efficacy by formulating mefloquine HCl nanoparticles. Mefloquine nanoparticles were formulated by emulsion diffusion method using polymer poly(ε-caprolactone) with six different formulations. Nanoparticles were characterized by determining its particle size, polydispersity index, drug entrapment efficiency, drug content, particle morphological character and drug release. The particle size ranged between 100 nm to 240 nm. Drug entrapment efficacy was >95%. The in-vitro release of nanoparticles were carried out which exhibited a sustained release of mefloquine HCl from nanoparticles up to 24 hrs. The results showed that nanoparticles can be a promising drug delivery system for sustained release of mefloquine HCl.

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