DESIGN AND IDENTIFY THE NOVEL PRIMAQUINE DERIVATIVES AS A POTENTIAL CANDIDATE DRUG AGAINST SELECTIVE ANTIBIOTIC-RESISTANT ORGANISMS

AbstractThe COVID-19 pandemic caused by the novel SARS-CoV-2 is more contagious than other coronaviruses and has higher rates of mortality than influenza. Identification of effective therapeutics is a crucial tool to treat those infected with SARS-CoV-2 and limit the spread of this novel disease globally. We deployed a bioinformatics workflow to identify candidate drugs for the treatment of COVID-19. Using an “omics” repository, the Library of Integrated Network-Based Cellular Signatures (LINCS), we simultaneously probed transcriptomic signatures of putative COVID-19 drugs and publicly available SARS-CoV-2 infected cell lines to identify novel therapeutics. We identified a shortlist of 20 candidate drugs: 8 are already under trial for the treatment of COVID-19, the remaining 12 have antiviral properties and 6 have antiviral efficacy against coronaviruses specifically, in vitro. All candidate drugs are either FDA approved or are under investigation. Our candidate drug findings are discordant with (i.e., reverse) SARS-CoV-2 transcriptome signatures generated in vitro, and a subset are also identified in transcriptome signatures generated from COVID-19 patient samples, like the MEK inhibitor selumetinib. Overall, our findings provide additional support for drugs that are already being explored as therapeutic agents for the treatment of COVID-19 and identify promising novel targets that are worthy of further investigation.

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Fucoxanthin and Colorectal Cancer Prevention

Cancers ◽

10.3390/cancers13102379 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2379

Author(s):

Masaru Terasaki ◽

Atsuhito Kubota ◽

Hiroyuki Kojima ◽

Hayato Maeda ◽

Kazuo Miyashita ◽

...

Keyword(s):

Colorectal Cancer ◽

Brown Algae ◽

Lifestyle Modification ◽

Signal Pathways ◽

Potential Candidate ◽

Anticancer Effects ◽

Cancer Models ◽

Candidate Drug ◽

Colorectal Cancer Prevention ◽

Dietary Carotenoid

Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.

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Susceptibility of Virulent Yersinia pestis Bacteria to Predator Bacteria in the Lungs of Mice

Microorganisms ◽

10.3390/microorganisms7010002 ◽

2018 ◽

Vol 7 (1) ◽

pp. 2 ◽

Cited By ~ 7

Author(s):

Riccardo Russo ◽

Irina Kolesnikova ◽

Thomas Kim ◽

Shilpi Gupta ◽

Androulla Pericleous ◽

...

Keyword(s):

Yersinia Pestis ◽

Bacterial Infections ◽

Treatment Modalities ◽

The Novel ◽

Global Public Health ◽

Antibiotic Resistant ◽

Colony Forming Units ◽

Tier 1 ◽

Predatory Bacteria ◽

Lethal Doses

Multi-drug resistant bacterial infections are a serious threat to global public health. Changes in treatment modalities and prudent use of antibiotics can assist in reducing the threat, but new approaches are also required for untreatable cases. The use of predatory bacteria, such as Bdellovibrio bacteriovorus, is among the novel approaches being considered as possible therapeutics for antibiotic resistant and/or unidentified bacterial infections. Previous studies have examined the feasibility of using predatory bacteria to reduce colony-forming units (CFUs) in the lungs of rats exposed to lethal doses of Klebsiella pneumoniae; here we apply the approach to the Tier 1 select agent Yersinia pestis, and show that three doses of B. bacteriovorus introduced every six hours reduces the number of CFUs of Y. pestis in the lungs of inoculated mice by 86% after 24 h of infection. These experiments further demonstrate that predatory bacteria may serve to combat Gram negative bacterial infections, including those considered potential bioweapon agents, in the future.

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HPLC-UV method for quantification of favipiravir in pharmaceutical formulations

Acta Chromatographica ◽

10.1556/1326.2020.00828 ◽

2020 ◽

Cited By ~ 1

Author(s):

İbrahim Bulduk

Keyword(s):

High Performance ◽

Potassium Dihydrogen Phosphate ◽

Pharmaceutical Formulations ◽

Hplc Method ◽

Dihydrogen Phosphate ◽

Potential Candidate ◽

Column Temperature ◽

Candidate Drug ◽

System Suitability ◽

Relative Standard

AbstractFavipiravir (FVP), a pyrazine analog, has shown antiviral activity against a wide variety of viruses. It is considered to be worth further investigation as a potential candidate drug for COVID-19. It is not officially available in any pharmacopoeia. A rapid, simple, precise, accurate, and isocratic high performance liquid chromatography (HPLC) method has been developed for routine quality control of favipiravir in pharmaceutical formulations. Separation was carried out by C18 column. The mobile phase was a mixture of 50 mM potassium dihydrogen phosphate (pH 2.3) and acetonitrile (90:10, v/v) at a flow rate of 1 mL min−1. The ultraviolet (UV) detection and column temperature were 323 nm, and 30 °C, respectively. The run time was 15 min under these chromatographic conditions. Excellent linear relationship between peak area and favipiravir concentration in the range of 10–100 μg mL−1 has been observed (r2, 0.9999). Developed method has been found to be sensitive (limits of detection and quantification were 1.20 μg mL−1 and 3.60 μg mL−1, respectively), precise (the interday and intraday relative standard deviation (RSD) values for peak area and retention time were less than 0.4 and 0.2%, respectively), accurate (recovery, 99.19–100.17%), specific and robust (% RSD were less than 1.00, for system suitability parameters). Proposed method has been successfully applied for quantification of favipiravir in pharmaceutical formulations.

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P-Glycoprotein Mediated Efflux Limits the Transport of the Novel Anti-Parkinson's Disease Candidate Drug FLZ across the Physiological and PD Pathological In Vitro BBB Models

PLoS ONE ◽

10.1371/journal.pone.0102442 ◽

2014 ◽

Vol 9 (7) ◽

pp. e102442 ◽

Cited By ~ 6

Author(s):

Qian Liu ◽

Jinfeng Hou ◽

Xiaoguang Chen ◽

Gengtao Liu ◽

Dan Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

The Novel ◽

P Glycoprotein ◽

Candidate Drug

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Novel Carbapenemases FLC-1 and IMI-2 Encoded by an Enterobacter cloacae Complex Isolated from Food Products

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.02338-18 ◽

2019 ◽

Vol 63 (6) ◽

Cited By ~ 4

Author(s):

Michael S. M. Brouwer ◽

Kamaleddin H. M. E. Tehrani ◽

Michel Rapallini ◽

Yvon Geurts ◽

Arie Kant ◽

...

Keyword(s):

General Population ◽

Enterobacter Cloacae ◽

Hydrolytic Activity ◽

Resistant Bacteria ◽

Human Consumption ◽

The Novel ◽

Antibiotic Resistant ◽

Content Type ◽

Class A ◽

Enterobacter Cloacae Complex

ABSTRACT Food for human consumption is screened widely for the presence of antibiotic-resistant bacteria to assess the potential for transfer of resistant bacteria to the general population. Here, we describe an Enterobacter cloacae complex isolated from imported seafood that encodes two carbapenemases on two distinct plasmids. Both enzymes belong to Ambler class A β-lactamases, the previously described IMI-2 and a novel family designated FLC-1. The hydrolytic activity of the novel enzyme against aminopenicillins, cephalosporins, and carbapenems was determined.

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Anticataractogenesis and Antiretinopathy Effects of the Novel Protective Agent Containing the Combined Extract of Mango and Vietnamese Coriander in STZ-Diabetic Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/5290161 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 3

Author(s):

Jintanaporn Wattanathorn ◽

Paphaphat Thiraphatthanavong ◽

Wipawee Thukham-mee ◽

Supaporn Muchimapura ◽

Panakaporn Wannanond ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Retinopathy ◽

Aldose Reductase ◽

Diabetic Rats ◽

Potential Candidate ◽

Protective Agent ◽

The Novel ◽

Diabetic Cataract ◽

Oxidative Stress Status ◽

Mango Seed

The novel protectant against diabetic cataract and diabetic retinopathy is currently required due to the increased prevalence and therapeutic limitation. Based on the advantage of polyphenol on diabetic eye complications, we hypothesized that the combined extract of mango seed Vietnamese coriander (MPO), a polyphenol-rich substance, should possess anticataractogenesis and antiretinopathy in streptozotocin- (STZ-) diabetic rats. MPO at doses of 2, 10, and 50 mg/kg·BW were orally given to STZ-diabetic rats for 10 weeks. Lens opacity was evaluated every week throughout a study period whereas the evaluation of cataract severity and histological changes of both rat lens epithelium and retina together with the biochemical assays of oxidative stress status, aldose reductase, p38MAPK, ERK1/2, and VEGF were performed at the end of experiment. Our data showed that MPO improved cataract and retinopathy in STZ-diabetic rats. The improved oxidative stress status and the decreased p38MAPK, ERK1/2, and VEGF were also observed. Therefore, anticataractogenesis and antiretinopathy of MPO might occur partly via the decreased oxidative stress status and the suppression of aldose reductase, p38MAPK, ERK1/2, and VEGF. This study points out that MPO is the potential candidate protectant against diabetic cataract and diabetic retinopathy. However, the exploration for possible active ingredient (S) still requires further researches.

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Development of a Novel Chimeric Endolysin, Lys109 With Enhanced Lytic Activity Against Staphylococcus aureus

Frontiers in Microbiology ◽

10.3389/fmicb.2020.615887 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bokyung Son ◽

Minsuk Kong ◽

Yoona Lee ◽

Sangryeol Ryu

Keyword(s):

Staphylococcus Aureus ◽

Stainless Steel ◽

Lytic Activity ◽

Domain Swapping ◽

Soluble Form ◽

Resistant Bacteria ◽

The Novel ◽

Planktonic Cells ◽

Antibiotic Resistant ◽

Modular Structures

As the incidence of antibiotic-resistant bacteria has become increased, phage endolysins are believed as one of the promising alternatives to antibiotics. However, the discovery of potent endolysin is still challenging because it is labor intensive and difficult to obtain a soluble form with high lytic activity. In this respect, the modular structures of Gram-positive endolysins can provide an opportunity to develop novel endolysins by domain rearrangement. In this study, a random domain swapping library of four different endolysins from phages infecting Staphylococcus aureus was constructed and screened to obtain engineered endolysins. The novel chimeric endolysin, Lys109 was selected and characterized for its staphylolytic activity. Lys109 exhibited greater bacterial cell lytic activity than its parental endolysins against staphylococcal planktonic cells and biofilms, showing highly improved activity in eliminating S. aureus from milk and on the surface of stainless steel. These results demonstrate that a novel chimeric endolysin with higher activity and solubility can be developed by random domain swapping and that this chimeric endolysin has a great potential as an antimicrobial agent.

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Berberine as a therapy for type 2 diabetes and its complications: From mechanism of action to clinical studies

Biochemistry and Cell Biology ◽

10.1139/bcb-2014-0107 ◽

2015 ◽

Vol 93 (5) ◽

pp. 479-486 ◽

Cited By ~ 55

Author(s):

Wenguang Chang ◽

Li Chen ◽

Grant M. Hatch

Keyword(s):

Type 2 Diabetes ◽

Clinical Studies ◽

Isoquinoline Alkaloid ◽

Pharmacological Therapy ◽

Potential Candidate ◽

Beneficial Effects ◽

Hypoglycemic Agent ◽

Candidate Drug ◽

Adults And Children

The incidence of type 2 diabetes is increasing rapidly worldwide, and the development of novel anti-diabetic drugs is emerging. However, most anti-diabetic drugs cannot be used in patients with hepatic dysfunction, renal disease, and heart disease, which makes pharmacological therapy of type 2 diabetes complicated. Despite continued introduction of novel agents, the search for an ideal drug that is useful as both a hypoglycemic agent and to reduce diabetes-related complications remains elusive. Berberine is an isoquinoline alkaloid extract that has shown promise as a hypoglycemic agent in the management of diabetes in animal and human studies. Mechanistic studies have revealed beneficial effects of berberine on diabetes-related complications. Although there have been few clinical reports of the anti-diabetic effects of berberine, little documentation of adverse effects in humans positions it as a potential candidate drug to treat type 2 diabetes. In the present review, the anti-diabetic mechanism of berberine, its effect on diabetes-related complications, and its recent use in human clinical studies is highlighted. In addition, we summarize the different treatments for type 2 diabetes in adults and children.

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