scholarly journals A Nature-Inspired Design Yields a New Class of Steroids Against Trypanosomatids

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3800
Author(s):  
Elena Aguilera ◽  
Cintya Perdomo ◽  
Alejandra Espindola ◽  
Ileana Corvo ◽  
Paula Faral-Tello ◽  
...  
Keyword(s):  
De Novo ◽  
Low Cost ◽  
World Health ◽  
New Class ◽  
The World ◽  
Low Toxicity ◽  
Health Organization ◽  
Toxicity In Vitro

Chagas disease and Leishmaniasis are neglected endemic protozoan diseases recognized as public health problems by the World Health Organization. These diseases affect millions of people around the world however, efficient and low-cost treatments are not available. Different steroid molecules with antimicrobial and antiparasitic activity were isolated from diverse organisms (ticks, plants, fungi). These molecules have complex structures that make de novo synthesis extremely difficult. In this work, we designed new and simpler compounds with antiparasitic potential inspired in natural steroids and synthesized a series of nineteen steroidal arylideneketones and thiazolidenehydrazines. We explored their biological activity against Leishmania infantum, Leishmania amazonensis, and Trypanosoma cruzi in vitro and in vivo. We also assayed their genotoxicity and acute toxicity in vitro and in mice. The best compound, a steroidal thiosemicarbazone compound 8 (ID_1260) was active in vitro (IC50 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in Leishmania and T. cruzi. It also has low toxicity in vitro and in vivo (LD50 >2000 mg/kg) and no genotoxic effects, being a promising compound for anti-trypanosomatid drug development.

scholarly journals SARS-CoV-2 detection with de novo designed synthetic riboregulators

2020 ◽  
Author(s):  
Ilkay Cisil Koksaldi ◽  
Recep Erdem Ahan ◽  
Sila Kose ◽  
Nedim Haciosmanoglu ◽  
Ebru Sahin Kehribar ◽  
...  
Keyword(s):  
De Novo ◽  
Point Of Care ◽  
Low Cost ◽  
Critical Role ◽  
World Health ◽  
Global Pandemic ◽  
Health Organization ◽  
Diagnostic Capabilities ◽  
Synthetic Biology Approach

Sars-CoV-2 is a human pathogen and is the main cause of COVID-19 disease. COVID-19 is announced as a global pandemic by World Health Organization. COVID-19 is characterized by severe conditions and early diagnosis can make dramatic changes both for personal and public health. In order to increase the reach for low cost equipment which requires a very limited technical knowledge can be beneficial to diagnose the viral infection. Such diagnostic capabilities can have a very critical role to control the transmission of the disease. Here we are reporting a state-of-the-art diagnostic tool developed by using an in vitro synthetic biology approach by employing engineered de novo riboregulators. Our design coupled with a home-made point-of-care device setting can detect and report presence of Sars-CoV-2 specific genes. The presence of Sars-CoV-2 related genes triggers translation of sfGFP mRNAs, resulting in green fluorescence output. The approach proposed here has the potential of being a game changer in Sars-COV-2 diagnostics by providing an easy-to-run, low-cost-demanding diagnostic capability.

scholarly journals Dietary Anthocyanins and Stroke: A Review of Pharmacokinetic and Pharmacodynamic Studies

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1479 ◽  
Author(s):  
Manolescu ◽  
Oprea ◽  
Mititelu ◽  
Ruta ◽  
Farcasanu
Keyword(s):  
Stroke Prevention ◽  
Mechanisms Of Action ◽  
World Health ◽  
Pharmacokinetic Studies ◽  
Cerebrovascular Accidents ◽  
The Third ◽  
The World ◽  
Health Organization

Cerebrovascular accidents are currently the second major cause of death and the third leading cause of disability in the world, according to the World Health Organization (WHO), which has provided protocols for stroke prevention. Although there is a multitude of studies on the health benefits associated with anthocyanin (ACN) consumption, there is no a rigorous systematization of the data linking dietary ACN with stroke prevention. This review is intended to present data from epidemiological, in vitro, in vivo, and clinical studies dealing with the stroke related to ACN-rich diets or ACN supplements, along with possible mechanisms of action revealed by pharmacokinetic studies, including ACN passage through the blood-brain barrier (BBB).

scholarly journals Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

Viruses ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 964 ◽  
Author(s):  
Andersen ◽  
Krpina ◽  
Ianevski ◽  
Shtaida ◽  
Jo ◽  
...  
Keyword(s):  
Influenza A ◽  
Rift Valley Fever Virus ◽  
Antiviral Agents ◽  
Viral Disease ◽  
World Health ◽  
Valley Fever ◽  
The World ◽  
Health Organization

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Repurposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here, we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FLUAV), niclosamide against HSV-2, brequinar against human immunodeficiency virus 1 (HIV-1), and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vitro and in vivo tests.

scholarly journals Therapeutic Emergence of Rhein as a Potential Anticancer Drug: A Review of Its Molecular Targets and Anticancer Properties

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2278 ◽  
Author(s):  
Sahu Henamayee ◽  
Kishore Banik ◽  
Bethsebie Lalduhsaki Sailo ◽  
Bano Shabnam ◽  
Choudhary Harsha ◽  
...  
Keyword(s):  
Cost Effective ◽  
World Health ◽  
Polygonum Multiflorum ◽  
Anticancer Properties ◽  
Helminthic Infections ◽  
Toxicological Studies ◽  
The World ◽  
Health Organization

According to the World Health Organization (WHO), cancer is the second-highest cause of mortality in the world, and it kills nearly 9.6 million people annually. Besides the fatality of the disease, poor prognosis, cost of conventional therapies, and associated side-effects add more burden to patients, post-diagnosis. Therefore, the search for alternatives for the treatment of cancer that are safe, multi-targeted, effective, and cost-effective has compelled us to go back to ancient systems of medicine. Natural herbs and plant formulations are laden with a variety of phytochemicals. One such compound is rhein, which is an anthraquinone derived from the roots of Rheum spp. and Polygonum multiflorum. In ethnomedicine, these plants are used for the treatment of inflammation, osteoarthritis, diabetes, and bacterial and helminthic infections. Increasing evidence suggests that this compound can suppress breast cancer, cervical cancer, colon cancer, lung cancer, ovarian cancer, etc. in both in vitro and in vivo settings. Recent studies have reported that this compound modulates different signaling cascades in cancer cells and can prevent angiogenesis and progression of different types of cancers. The present review highlights the cancer-preventing and therapeutic properties of rhein based on the available literature, which will help to extend further research to establish the chemoprotective and therapeutic roles of rhein compared to other conventional drugs. Future pharmacokinetic and toxicological studies could support this compound as an effective anticancer agent.

scholarly journals Antischistosomal Activity of Zingiber officinale, Piper nigrum, and Coriandrum sativum Aqueous Plant Extracts on Hamster Infected with Schistosoma mansoni

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Mohamed F. Abou El-Nour ◽  
Yousef Fadladdin
Keyword(s):  
Schistosoma Mansoni ◽  
Zingiber Officinale ◽  
Coriandrum Sativum ◽  
World Health ◽  
Piper Nigrum ◽  
The World ◽  
Antischistosomal Activity ◽  
Health Organization

Schistosomiasis continues to affect the health and quality of life of millions of people around the world. Schistosomiasis has been ranked the second disease after malaria in terms of importance as a targeted tropical disease. Praziquantel (PZQ) is the only drug approved by the World Health Organization (WHO) for the treatment of schistosomiasis. Being the only drug, parasite resistance to this drug has developed. Therefore, the search for new alternatives has been the goal of many researchers. In this study, the effects of aqueous extracts of Zingiber officinale, Piper nigrum, and Coriandrum sativum on Schistosoma mansoni infected golden hamsters (Egyptian strain) were evaluated in vitro and in vivo at different doses of 500, 250, 125, 62.5, and 31.25 μg/ml. In vitro, adult worms of S. mansoni were tested in RPMI-1640 medium for 48 hrs. The results showed that the concentrations 500, 250, and 125 μg/ml of Zingiber officinale and Piper nigrum caused dead of 100% of adult worms within 6 and 12 hrs of incubation, respectively. Although, aqueous extract of Coriandrum sativum at concentrations 500, 250, and 125 μg/ml resulted dead of 100% parasites after 12 to 24 hrs of incubation. In conclusion, Zingiber officinale and Piper nigrum showed efficacy against schistosomiasis in both in vitro and biological experiments of Egyptian schistosome strain, while Coriandrum sativum gave less effective results than the previous ones. Therefore, Zingiber officinale and Piper nigrum may become an innovative treatment for schistosomiasis.

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.

Antimicrobial peptides for the treatment of pulmonary tuberculosis, allies or foes?

2018 ◽  
Vol 24 (10) ◽  
pp. 1138-1147
Author(s):  
Bruno Rivas-Santiago ◽  
Flor Torres-Juarez
Keyword(s):  
Pulmonary Tuberculosis ◽  
Antimicrobial Peptides ◽  
Experimental Models ◽  
New Drugs ◽  
World Health ◽  
Public Health Issue ◽  
Health Organization ◽  
Drug Resistant Strains

Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of World Health Organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the Antimicrobial Peptides (AMPs). These peptides have demonstrated remarkable efficacy to kill mycobacteria in vitro and in vivo in experimental models, nevertheless, these peptides not only have antimicrobial activity but also have a wide variety of functions such as angiogenesis, wound healing, immunomodulation and other well-described roles into the human physiology. Therapeutic strategies for tuberculosis using AMPs must be well thought prior to their clinical use; evaluating comorbidities, family history and risk factors to other diseases, since the wide function of AMPs, they could lead to collateral undesirable effects.

scholarly journals Virtual Screening and Statistical Analysis in the Design of New Caffeine Analogues Molecules with Potential Epithelial Anticancer Activity

2018 ◽  
Vol 24 (5) ◽  
pp. 576-594 ◽  
Author(s):  
Josivan da Silva Costa ◽  
Karina da Silva Lopes Costa ◽  
Josiane Viana Cruz ◽  
Ryan da Silva Ramos ◽  
Luciane Barros Silva ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Binding Free Energy ◽  
Inhibitory Effect ◽  
Parametric Models ◽  
World Health ◽  
Pharmacokinetic Properties ◽  
Clinically Significant ◽  
Health Organization

About 132 thousand cases of melanoma (more severe type of skin cancer) were registered in 2014 according to the World Health Organization. This type of cancer significantly affects the quality of life of individuals. Caffeine has shown potential inhibitory effect against epithelial cancer. In this study, it was proposed to obtain new caffeine-based molecules with potential epithelial anticancer activity. For this, a training set of 21 molecules was used for pharmacophore perception procedures. Multiple linear regression analyses were used to propose mono-, bi-, tri-, and tetra-parametric models applied in the prediction of the activity. The generated pharmacophore was used to select 350 molecules available at the ZINCpharmer server, followed by reduction to 24 molecules, after selection using the Tanimoto index, yielding 10 molecules after final selection by predicted activity values > 1.5229. These ten molecules had better pharmacokinetic properties than the other ones used as reference and within the clinically significant limits. Only two molecules show minor hits of toxicity and were submitted to molecular docking procedures, showing BFE (binding free energy) values lower than the reference values. Statistical analyses indicated strong negative correlations between BFE and pharmacophoric properties (high influence on BFE lowering) and practically null correlation between BFE and BBB. The two most promising molecules can be indicated as candidates for further in vitro and in vivo analyzes.

scholarly journals Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine

2019 ◽  
Author(s):  
Petter I. Andersen ◽  
Klara Krpina ◽  
Aleksandr Ianevski ◽  
Nastassia Shtaida ◽  
Eunji Jo ◽  
...  
Keyword(s):  
Influenza A ◽  
Rift Valley Fever Virus ◽  
Antiviral Agents ◽  
Viral Disease ◽  
World Health ◽  
Valley Fever ◽  
The World ◽  
Health Organization ◽  
Hiv 1

Viruses are the major causes of acute and chronic infectious diseases in the world. According to the World Health Organization, there is an urgent need for better control of viral diseases. Re-purposing existing antiviral agents from one viral disease to another could play a pivotal role in this process. Here we identified novel activities of obatoclax and emetine against herpes simplex virus type 2 (HSV-2), human immunodeficiency virus 1 (HIV-1), echovirus 1 (EV1), human metapneumovirus (HMPV) and Rift Valley fever virus (RVFV) in cell cultures. Moreover, we demonstrated novel activities of emetine against influenza A virus (FluAV), niclosamide against HSV-2, brequinar against HIV-1, and homoharringtonine against EV1. Our findings may expand the spectrum of indications of these safe-in-man agents and reinforce the arsenal of available antiviral therapeutics pending the results of further in vivo tests.

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