Synthesis of Novel 1,2,3-Triazole Derivatives of Isocoumarins and 3,4-Dihydroisocoumarin with Potential Antiplasmodial Activity In Vitro

2020 ◽  
Vol 16 ◽  
Author(s):  
Lucas da Silva Santos ◽  
Matheus Fillipe Langanke de Carvalho ◽  
Ana Claudia de Souza Pinto ◽  
Amanda Luisa da Fonseca ◽  
Julio César Dias Lopes ◽  
...  
Keyword(s):  
Triazole Ring ◽  
Antiplasmodial Activity ◽  
World Health ◽  
Dipolar Cycloaddition ◽  
Terminal Alkynes ◽  
The World ◽  
Ic50 Values ◽  
Derivatives Of ◽  
Active Substances

Background: Malaria greatly affects the world health, having caused more than 228 million cases only in 2018. The emergence of drug resistance is one of the main problems in its treatment, demonstrating the urge for the development of new antimalarial drugs. Objective: Synthesis and in vitro antiplasmodial evaluation of triazole compounds derived from isocoumarins and a 3,4- dihydroisocoumarin. Method: The compounds were synthesized in 4 to 6-step reactions with the formation of the triazole ring via the Copper(I)-catalyzed 1,3-dipolar cycloaddition between isocoumarin or 3,4-dihydroisocoumarin azides and terminal alkynes. This key reaction provided compounds with an unprecedented connection of isocoumarin or 3,4-dihydroisocoumarin and the 1,2,3-triazole ring. The products were tested for their antiplasmodial activity against a Plasmodium falciparum chloroquine resistant and sensitive strains (W2 and 3D7, respectively). Results: Thirty-one substances were efficiently obtained by the proposed routes with an overall yield of 25-53%. The active substances in the antiplasmodial test displayed IC50 values ranging from 0.68-2.89 μM and 0.85-2.07 μM against W2 and 3D7 strains, respectively.

Natural products from the traditional Moroccan pharmacopoeia: A potential lead for the prevention and treatment of COVID-19

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 1278-1285
Author(s):  
Mohamed Yafout ◽  
Amine Ousaid ◽  
Ibrahim Sbai El Otmani ◽  
Youssef Khayati ◽  
Amal Ait Haj Said
Keyword(s):  
Medicinal Plants ◽  
Plant Extracts ◽  
Molecular Mechanisms ◽  
Scientific Literature ◽  
Treatment Protocol ◽  
World Health ◽  
The World ◽  
Health Organization ◽  
Promising Source

The new SARS-CoV-2 belonging to the coronaviruses family has caused a pandemic affecting millions of people around the world. This pandemic has been declared by the World Health Organization as an international public health emergency. Although several clinical trials involving a large number of drugs are currently underway, no treatment protocol for COVID-19 has been officially approved so far. Here we demonstrate through a search in the scientific literature that the traditional Moroccan pharmacopoeia, which includes more than 500 medicinal plants, is a fascinating and promising source for the research of natural molecules active against SARS-CoV-2. Multiple in-silico and in-vitro studies showed that some of the medicinal plants used by Moroccans for centuries possess inhibitory activity against SARS-CoV or SARS-CoV-2. These inhibitory activities are achieved through the different molecular mechanisms of virus penetration and replication, or indirectly through stimulation of immunity. Thus, the potential of plants, plant extracts and molecules derived from plants that are traditionally used in Morocco and have activity against SARS-CoV-2, could be explored in the search for a preventive or curative treatment against COVID-19. Furthermore, safe plants or plant extracts that are proven to stimulate immunity could be officially recommended by governments as nutritional supplements.

Treatment Options in COVID-19: The Role of Bioavailable Antiviral Ribonucleoside Analog on NHC in vitro

2020 ◽  
Author(s):  
Lara Bittmann
Keyword(s):  
World Health Organization ◽  
Clinical Picture ◽  
Treatment Options ◽  
World Health ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.

New Efavirenz Derivatives and 1,2,3-Triazolyl-phosphonates as Inhibitors of Reverse Transcriptase of HIV-1

2018 ◽  
Vol 18 (17) ◽  
pp. 1494-1505 ◽  
Author(s):  
Carolina C.P. Costa ◽  
Nubia Boechat ◽  
Monica M. Bastos ◽  
Fernando de C. da Silva ◽  
Andressa Marttorelli ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Triazole Ring ◽  
Biological Evaluation ◽  
World Health ◽  
Hiv Reverse Transcriptase ◽  
Ic50 Values ◽  
Health Organization ◽  
Hiv Drugs ◽  
Immunodeficiency Syndrome ◽  
New Compounds

Background: According to the World Health Organization (WHO), the fight against Acquired Immunodeficiency Syndrome (AIDS) is still one of the most significant challenges facing humanity. Worldwide, it is estimated that 36.7 million people are infected by the Human Immunodeficiency Virus (HIV). Despite the variety of available drugs, the search for new enzymatic inhibitors of HIV is still important due to the presence of adverse effects and the development of resistant strains. Therefore, the present study aimed to design, synthesize, and biologically evaluate novel inhibitors of HIV Reverse Transcriptase (RT). Materials and Methods: These compounds were obtained in two series, and compounds in both series contain a 1,2,3-triazole ring in their structures. The compounds in the first series are Efavirenz (EFV) analogues with the N-1 position substituted by another important fragment as described in the medicinal chemistry literature on anti-HIV drugs. The second series has a phosphonate chain similar to that in the structure of Tenofovir Disoproxil Fumarate (TDF). Results and Conclusion: The results of the biological evaluation showed that all compounds presented high RT inhibition values and lower or comparable inhibitory concentrations (the concentration needed to reduce the enzymatic activity by 50%, IC50 values, 0.8-1.9 µM). Among the compounds in the first series, the three with the lowest IC50 values had values between 0.8-0.9 µM, and of those in the second series, the most potent had an IC50 value of 1.1 µM; compounds in both series were equipotent to TDF (1.2 µM). Thus, the new compounds could be considered lead compounds for the development of new antiretroviral compounds.

scholarly journals Seroprevalence of SARS-CoV-2, Symptom Profiles and Sero-Neutralization in a Suburban Area, France

Viruses ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1076
Author(s):  
Anne Gégout Petit ◽  
Hélène Jeulin ◽  
Karine Legrand ◽  
Nicolas Jay ◽  
Agathe Bochnakian ◽  
...  
Keyword(s):  
Odds Ratio ◽  
World Health Organisation ◽  
World Health ◽  
Preventive Effect ◽  
Neutralization Activity ◽  
Symptom Profiles ◽  
The World ◽  
Household Members ◽  
Total Immunoglobulin

The World Health Organisation recommends monitoring the circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We investigated anti–SARS-CoV-2 total immunoglobulin (IgT) antibody seroprevalence and in vitro sero-neutralization in Nancy, France, in spring 2020. Individuals were randomly sampled from electoral lists and invited with household members over 5 years old to be tested for anti–SARS-CoV-2 (IgT, i.e., IgA/IgG/IgM) antibodies by ELISA (Bio-rad); the sero-neutralization activity was evaluated on Vero CCL-81 cells. Among 2006 individuals, the raw seroprevalence was 2.1% (95% confidence interval 1.5 to 2.9), was highest for 20- to 34-year-old participants (4.7% (2.3 to 8.4)), within than out of socially deprived area (2.5% vs. 1%, p = 0.02) and with than without intra-family infection (p < 10−6). Moreover, 25% of participants presented at least one COVID-19 symptom associated with SARS-CoV-2 positivity (p < 10−13), with highly discriminant anosmia or ageusia (odds ratio 27.8 [13.9 to 54.5]); 16.3% (6.8 to 30.7) of seropositive individuals were asymptomatic. Positive sero-neutralization was demonstrated in vitro for 31/43 seropositive subjects. Regarding the very low seroprevalence, a preventive effect of the lockdown in March 2020 can be assumed for the summer, but a second COVID-19 wave, as expected, could be subsequently observed in this poorly immunized population.

scholarly journals Assessment of Antimalarial Activity againstPlasmodium falciparumand Phytochemical Screening of Some Yemeni Medicinal Plants

2009 ◽  
Vol 6 (4) ◽  
pp. 453-456 ◽  
Author(s):  
Mohammed A. Alshawsh ◽  
Ramzi A. Mothana ◽  
Hassan A. Al-shamahy ◽  
Salah F. Alsllami ◽  
Ulrike Lindequist
Keyword(s):  
Medicinal Plants ◽  
Antimalarial Activity ◽  
Traditional Healers ◽  
Antiplasmodial Activity ◽  
World Health ◽  
Moderate Activity ◽  
Phytochemical Screening ◽  
Cissus Rotundifolia ◽  
Health Organization

Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa,Azadirachta indica,Cissus rotundifolia,Echium rauwalfii,Dendrosicyos socotranaandBoswellia elongata) commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates ofPlasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured byin vitromicro test (Mark III) according to World Health Organization (WHO) 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC50values less than 4 µg/ml, namely the water extracts ofA. fruticosa,A. indicaandD. socotrana. Six extracts showed moderate activity with IC50values ranging from 10 to 30 µg/ml and three appeared to be inactive with IC50values more than 30 µg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides.

scholarly journals A Review of the Preclinical and Clinical Efficacy of Remdesivir, Hydroxychloroquine, and Lopinavir-Ritonavir Treatments against COVID-19

2020 ◽  
Vol 25 (10) ◽  
pp. 1108-1122 ◽  
Author(s):  
Dawid Maciorowski ◽  
Samir Z. El Idrissi ◽  
Yash Gupta ◽  
Brian J. Medernach ◽  
Michael B. Burns ◽  
...  
Keyword(s):  
Gastrointestinal Symptoms ◽  
High Risk Group ◽  
Capital City ◽  
World Health ◽  
Atypical Pneumonia ◽  
Live Animal ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

In December of 2019, an outbreak of a novel coronavirus flared in Wuhan, the capital city of the Hubei Province, China. The pathogen has been identified as a novel enveloped RNA beta-coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus SARS-CoV-2 is associated with a disease characterized by severe atypical pneumonia known as coronavirus 2019 (COVID-19). Typical symptoms of this disease include cough, fever, malaise, shortness of breath, gastrointestinal symptoms, anosmia, and, in severe cases, pneumonia.1 The high-risk group of COVID-19 patients includes people over the age of 60 years as well as people with existing cardiovascular disease and/or diabetes mellitus. Epidemiological investigations have suggested that the outbreak was associated with a live animal market in Wuhan. Within the first few months of the outbreak, cases were growing exponentially all over the world. The unabated spread of this deadly and highly infectious virus is a health emergency for all nations in the world and has led to the World Health Organization (WHO) declaring a pandemic on March 11, 2020. In this report, we consolidate and review the available clinically and preclinically relevant results emanating from in vitro animal models and clinical studies of drugs approved for emergency use as a treatment for COVID-19, including remdesivir, hydroxychloroquine, and lopinavir-ritonavir combinations. These compounds have been frequently touted as top candidates to treat COVID-19, but recent clinical reports suggest mixed outcomes on their efficacies within the current clinical protocol frameworks.

scholarly journals O-Aminoalkyl-O-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3142 ◽  
Author(s):  
Bao Vue ◽  
Sheng Zhang ◽  
Andre Vignau ◽  
Guanglin Chen ◽  
Xiaojie Zhang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Apoptosis ◽  
Prostate Cancer Cell ◽  
Synthetic Methods ◽  
Step Procedure ◽  
Ic50 Values ◽  
In Vitro Effects ◽  
Synthetic Approaches ◽  
Derivatives Of

As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40–3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G0/G1 phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.

scholarly journals Callus of American ginseng (Panax quinquefolius) as a source of ginsenosides – medicinal secondary metabolites

2013 ◽  
Vol 50 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Ewa Kochan ◽  
Aleksander Chmiel
Keyword(s):  
North America ◽  
Secondary Metabolites ◽  
Traditional Medicine ◽  
Panax Ginseng ◽  
American Ginseng ◽  
Panax Quinquefolius ◽  
In Vitro Methods ◽  
Derivatives Of ◽  
Active Substances

Abstract:Asian ginseng (Panax ginseng) and American ginseng (P. quinquefolius) are valuable medicinal herbs whose roots have been used for ages in traditional medicine in China and North America as vitalizing and stimulating agents. The roots are obtained mainly from field cultivation, which is a slow (5-7 years long), laborious, and troublesome process; so in vitro methods started to be used to produce ginseng biomass. In our study, non-organogenic callus of P. quinquefolius synthesized the same active substances like field roots, for more than 6 years. The ginsenosides are derivatives of protopanaxadiol (Rb1, Rb2, Rc, Rd) or protopanaxatriol (Rg1, Re). The synthesis of Rg1and Re metabolites is preferred in calli cultured in the dark and with ageing of culture.

Effect of Panax notoginseng Extracts on Inferior Sperm Motility in vitro

1999 ◽  
Vol 27 (01) ◽  
pp. 123-128 ◽  
Author(s):  
Jung-Chou Chen ◽  
Ming-Xiong Xu ◽  
Leih-Der Chen ◽  
Yan-Nian Chen ◽  
Tsan Hung Chiu
Keyword(s):  
Sperm Motility ◽  
Sperm Count ◽  
Semen Analysis ◽  
Panax Notoginseng ◽  
World Health ◽  
Computer Assisted ◽  
Butanol Extract ◽  
The World ◽  
Health Organization

The purpose of this study was to investigate the effects of Panax notoginseng extracts on inferior sperm motility in vitro. Semen samples were collected from 23 patients with sperm motility between 20% and 40%. The sperm count was over 20 × 106/ml in accordance with the World Health Organization standard. 1.0 mg/ml and 2.0 mg/ml of Panax notoginseng extracts including aqueous extract, n-butanol extract, and polysaccharide fraction on sperm motility and progression were evaluated by computer assisted semen analysis. The results demonstrated that sperm motility as well as progression on inferior sperm motility were enhanced at 1 hour and 2 hours after incubation with all three types of extracts.

Sign in / Sign up

Export Citation Format

Share Document