Repurposing of Existing Statin Drugs for Treatment of Microbial Infections: How Much Promising?

2019 ◽  
Vol 19 (3) ◽  
pp. 224-237 ◽  
Author(s):  
Ritika Rana ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Infectious Diseases ◽  
Antimicrobial Agents ◽  
Cost Effective ◽  
New Drugs ◽  
Pharmaceutical Companies ◽  
Major Barrier ◽  
Microbial Infections ◽  
Approved Drugs ◽  
Statin Drugs ◽  
Novel Drug

Today’s microbial infections’ resistance to approved drugs, the emergence of new infectious diseases and lack of vaccines, create a huge threat to human health. Thus, there is an urgent need to create novel antimicrobial agents, but the high cost and prolonged timeline of novel drug discovery and development is the major barrier to make new drugs. Therefore, there is a need for specific cost effective approaches in order to identify new drugs for the treatment of various microbial infections. Drug repurposition is an alternative technique to find existing clinically approved drugs for other indications. This approach may enhance the portfolio of Pharmaceutical companies by reducing the time and money required for the development of new chemical entity. In literature, various studies have reported some encouraging results regarding the antimicrobial use of existing statin drugs. Further, some clinical studies have also shown the protective effect of statin drugs in reduction of the morbidity and mortality due to many infectious diseases but complete understanding is still lacking. Thus, there is a need for better understanding of the use of statin drugs, especially in the context of antimicrobial effects. In this review, we try to summarize the use of statin drugs in various infectious diseases and their proposed antimicrobial mechanism of action. Further, current challenges and future perspectives of repurposition of statin drugs as antimicrobial agents have also been discussed.

Comparison of Minimum Inhibitory Concentration (MIC) value of statin drugs: A Systematic Review

2018 ◽  
Vol 17 (1) ◽  
pp. 4-19 ◽  
Author(s):  
Meenakshi Gupta ◽  
Anoop Kumar
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Synergetic Effect ◽  
Microbial Infection ◽  
Microbial Infections ◽  
Approved Drugs ◽  
Almost All ◽  
Statin Drugs ◽  
Mic Value

Background: Microbial infection and its resistance to clinically approved drugs create a huge threat to human health. Emerging reports have indicated the potential of statin drugs in the treatment of various types of microbial infections. However, it is still unclear, how much concentration of statin is effective against microbial infections. In literature, Minimum Inhibitory Concentration (MIC) values of statin drugs vary according to strain, species, and the type of statins. Thus, the main aim of the current study is to compare the MIC values of various types of statins against various types of micro-organisms. The data related to statin and microbial infection has been extracted from Pub Med (from September 1 Methodology: 987 to October 2017). A total of 662 studies have been published from 1987 -2017 regarding statin and microbial infections. After inclusion and exclusion criteria, finally, 28 studies have been selected for comparative analysis of MIC values. Results: All the statin drugs have shown a significant effect on various types of microbial infections. Among all the tested statin drugs, Simvastatin has lower MIC value in almost all types of microorganisms as compared to other statin drugs. However, on S. pneumoniae and aspergillus, Fluvastatin has the lowest MIC values as compared to Simvastatin. Atorvastatin was found to be the most potent against almost all strains of gram-negative bacteria. However, Rosuvastatin and Pravastatin have high MIC value against all types of microorganisms. Further, FICI value indicated the synergetic effect of Simvastatin with Amphotericin B, Itraconazole, and Fluconazole against various strains of Cryptococcus. Conclusion: In conclusion, Simvastatin, Atorvastatin, and Fluvastatin could be developed as potential antimicrobial agents. However, further studies are required to understand its complete safety and efficacy profile..

Selective Estrogen Receptor Modulators (SERMs): Mechanistic Insights Against Microbial Infections

2020 ◽  
Vol 20 (2) ◽  
pp. 102-115
Author(s):  
Aakriti Garg ◽  
Balraj Singh ◽  
Ruchika Sharma ◽  
Arti Singh ◽  
Anoop Kumar
Keyword(s):  
Estrogen Receptor ◽  
Antimicrobial Agents ◽  
Antimicrobial Property ◽  
Selective Estrogen Receptor Modulators ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Level Of Evidence ◽  
Estrogen Receptor Modulators ◽  
Microbial Infections ◽  
Receptor Modulators

Background: Infections are one of the leading causes of death worldwide and currently available treatments remain unsatisfactory due to rise in the cases of antimicrobial resistance. Thus, there is a need for the development of new drugs with different mechanisms of action. However, the development of new antimicrobials agents is a long and expensive process. Hence, most of the pharmaceutical companies are Methodology: The data related to SERMs and microbial infection has been extracted from Pub Med (from January 1997 to December 2018). A total of 101 studies have been published from 1997 -2018 regarding SERMs and microbial infections. Results: On the basis of inclusion and exclusion criteria, 25 studies have been included for the analysis of level of evidence regarding antimicrobial effects of SERMs. Emerging reports have indicated the antimicrobial property of selective estrogen receptor modulators (SERMs) against normal and resistant strains under in vitro and in vivo conditions against wide variety of microorganisms through different mechanisms of action. Conclusion: In conclusion, SERMs could be developed as a broad spectrum antimicrobial agent alone or in combination with existing antimicrobial agents.

Review on few South Indian medicinal plants as antimicrobial agents

2016 ◽  
Vol 5 (03) ◽  
pp. 4915
Author(s):  
Phani Kumari Uddandapu* ◽  
Venkateswar Rao, Y. ◽  
Chandrasekhara Naidu K.
Keyword(s):  
Medicinal Plants ◽  
Infectious Diseases ◽  
Human Health ◽  
Antimicrobial Agents ◽  
Well Being ◽  
New Drugs ◽  
South Indian ◽  
Medicinal Properties ◽  
Health And Well Being ◽  
Indian Medicinal Plants

The Plant kingdom is a storehouse of potential drugs. Plant derived medicines have made large contributions to human health and well-being. They play dual role in the development of new drugs. At first they act as a natural blueprint for the development of new drugs and secondly they can be used for the treatment of infectious diseases. Many evidences gathered from earlier studies which confirmed that the presence of variety of phytochemicals in plants contribute medicinal properties. In this present review, an attempt has been made to give an overview of few south Indian medicinal plants and their phytochemicals which are useful in the treatment of several infectious diseases.

scholarly journals Measuring clinical trial transparency: an empirical analysis of newly approved drugs and large pharmaceutical companies

BMJ Open ◽  
2017 ◽  
Vol 7 (12) ◽  
pp. e017917 ◽  
Author(s):  
Jennifer E Miller ◽  
Marc Wilenzick ◽  
Nolan Ritcey ◽  
Joseph S Ross ◽  
Michelle M Mello
Keyword(s):  
Clinical Trial ◽  
Descriptive Analysis ◽  
Drug Level ◽  
Drug Approval ◽  
Securities And Exchange Commission ◽  
New Drugs ◽  
Pharmaceutical Companies ◽  
Cross Sectional ◽  
Fda Approval ◽  
Approved Drugs

ObjectivesTo define a series of clinical trial transparency measures and apply them to large pharmaceutical and biotechnology companies and their 2014 FDA-approved drugs.DesignCross-sectional descriptive analysis of all clinical trials supporting 2014 Food and Drugs Administration (FDA)-approved new drug applications (NDAs) for novel drugs sponsored by large companies.Data sourcesData from over 45 sources, including [email protected], ClinicalTrials.gov, corporate and international registries; PubMed, Google Scholar, EMBASE, corporate press releases, Securities and Exchange Commission (SEC) filings and personal communications with drug manufacturers.Outcome measuresTrial registration, results reporting, clinical study report (CSR) synopsis sharing, biomedical journal publication, and FDA Amendments Acts (FDAAA) compliance, analysed on the drug level.ResultsThe FDA approved 19 novel new drugs, sponsored by 11 large companies, involving 553 trials, in 2014. We analysed 505 relevant trials. Per drug, a median of 100% (IQR 86%–100%) of trials in patients were registered, 71% (IQR 57%–100%) reported results or shared a CSR synopsis, 80% (70%–100%) were published and 96% (80%–100%) were publicly available in some form by 13 months after FDA approval. Disclosure rates were lower at FDA approval (65%) and improved significantly by 6 months post FDA approval. Per drug, a median of 100% (IQR 75%–100%) of FDAAA-applicable trials were compliant. Half of reviewed drugs had publicly disclosed results for all trials in patients in our sample. One trial was uniquely registered in a corporate registry, and not ClinicalTrials.gov; 0 trials were uniquely registered in international registries.ConclusionsAmong large pharmaceutical companies and new drugs, clinical trial transparency is high based on several standards, although opportunities for improvement remain. Transparency is markedly higher for trials in patients than among all trials supporting drug approval, including trials in healthy volunteers. Ongoing efforts to publicly track companies’ transparency records and recognise exemplary companies may encourage further progress.

scholarly journals A Protocol for Identifying Potentially Repurposable Drugs Using Online Tools and Databases

2016 ◽  
Author(s):  
Aditi Chattopadhyay ◽  
Madhavi Ganapathiraju
Keyword(s):  
In Silico ◽  
Small Cell Lung Carcinoma ◽  
Drug Repurposing ◽  
Cost Effective ◽  
Age Related Macular Degeneration ◽  
New Drugs ◽  
Compound Identification ◽  
Cell Lung Carcinoma ◽  
Age Related ◽  
Approved Drugs

Traditional methods for discovery and development of new drugs can be a very time-consuming and expensive process because it includes several stages such as compound identification, pre-clinical and clinical trials before the drug is approved by the US Food and Drug Administration (FDA). Therefore, drug repurposing, namely using currently FDA-approved drugs as therapeutics for other diseases than what they are originally prescribed for, is emerging to be a faster and more cost-effective alternative to current drug discovery methods. In this paper, we have described a three-step in silico protocol for analyzing transcriptomics data using online databases and bioinformatics tools for identifying potentially repurposable drugs. The efficacy of this protocol was evaluated by comparing its predictions with the findings of two case studies of recently reported repurposed drugs: HIV treating drug Zidovudine for the treatment of Dry Age-Related Macular Degeneration and the antidepressant Imipramine for Small-Cell Lung Carcinoma. The proposed protocol successfully identified the published findings, thus demonstrating the efficacy of this method. In addition, it also yielded several novel predictions that have not yet been published, including the finding that Imipramine could potentially treat Severe Acute Respiratory Syndrome (SARS), a disease that currently does not have any treatment or vaccine. Since this in-silico protocol is simple to use and does not require advanced computer skills, we believe any motivated participant with access to these databases and tools would be able to apply it to large datasets to identify other potentially repurposable drugs in the future.

scholarly journals Multiple Myeloma :Trends in Consulting Fees and Drug Utilization

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5823-5823
Author(s):  
Daniel Chakos ◽  
Azam Farooqui ◽  
Kimberly McCormick ◽  
Abhishek R Chilkulwar
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Monoclonal Antibodies ◽  
Healthcare System ◽  
Conflicts Of Interest ◽  
New Drugs ◽  
Pharmaceutical Companies ◽  
The Past ◽  
Approved Drugs ◽  
The Cost

Introduction Per the National Cancer Institute epidemiological data, the incidence of multiple myeloma has not changed significantly over the past decade. Mortality from myeloma has not changed significantly between 2007-2016 with an estimated 5-year survival of 55.2 % between 2009-2015. The treatment of multiple myeloma has improved significantly over the past decade with the approval of several new drugs. In the recent IFM trial, the 4-year overall survival in a select group of myeloma patients was 82% when treated with bortezomib, lenalidomide and dexamethasone followed by autologous stem cell transplant and maintenance therapy. These numbers may further improve with approval of monoclonal antibodies and several new drugs in clinical trials. The cost of healthcare has been growing consistently for the past several years. Per CMS data, healthcare spending grew 3.7% in 2017 reaching $3.5 trillion, or $10,739 per person. National health spending is projected to grow at a rate of 5.5% per year from 2018-2027 reaching nearly $6.0 trillion. Health share of the GDP is expected to rise from 17.9% to 19.4%. Pharmaceutical costs have been rising consistently over the past several years with cancer therapies being some of the costliest. Most new cancer therapy costs more than $100,000 per year with the triplet combinations for myeloma costing upwards of $200,000 per year. Methods Our goal was to evaluate the utilization of the newer drugs approved for myeloma by the Medicare population and assess the economic burden of growing drug prices on the health care system. We queried the national CMS database from 2013-2017 to obtain information on Medicare payments made, number of providers making claims and consulting fees for bortezomib, carfilzomib, daratumumab, elotuzumab, ixazomib, lenalidomide, panobinostat and pomalidomide. Results Between 2013-2017 there has been a significant increase in the annual Medicare payments made for myeloma drugs. The amount of payments has tripled between 2013-2017. The number of claims made and providers making those claims have increased. There has also been an exponential increase in consulting fees paid by various pharmaceutical companies to promote prescription of the aforementioned drugs. The amount of money paid in consultation has nearly quadrupled since 2013. Results are consolidated in Table 1 and Figure 1. Discussion This past decade has been an exciting period in cancer research and drug approvals, with myeloma being one of the many malignancies benefitting from this progress. This was made possible by the collaboration between pharmaceutical companies and academic institutions. With the need for continuous combination therapy in multiple myeloma along with increasing prices of existing drugs and high upfront market prices for newly approved drugs, there is significant financial burden placed on the healthcare system. Based on the published literature substitution of carfilzomib for bortezomib or addition of monoclonal antibodies in induction would double cost. Some of these drug approvals are based solely on surrogate endpoints of overall response rates and progression free survival benefit of few months. This is without proven overall survival data while harboring significant toxicity. Conclusion: With pharmaceutical companies spending millions of dollars for drug development there has been a trend towards higher drug pricing. These companies also pay large amounts of consulting fees to physicians dedicated to aggressively market these newly approved drugs which are priced higher than existing therapy. Some of the current cancer guidelines include authors who have financial conflicts of interest and receive consulting fees from pharmaceutical companies. It would be interesting to investigate the correlation between the consulting fees and its effect on prescription patterns. Even the cancer care guidelines do not consider the cost effectiveness of equally effective regimens. There has been a push from various pioneers in the field to incorporate value-based recommends into their guidelines. Given the trajectory of rising costs within our healthcare system, it is imperative for all physicians to be mindful of value-based care while seeking therapy options that provide true benefit to their vulnerable patient populations. Disclosures No relevant conflicts of interest to declare.

Repurposing of Existing Drugs for the Bacterial Infections: An In silico and In vitro Study

2020 ◽  
Vol 20 (2) ◽  
pp. 182-197 ◽  
Author(s):  
Yachika Kapoor ◽  
Ruchika Sharma ◽  
Anoop Kumar
Keyword(s):  
Infectious Diseases ◽  
In Silico ◽  
Bacterial Infections ◽  
In Vitro Study ◽  
Treatment Modalities ◽  
Current Investigation ◽  
Microbial Infections ◽  
Approved Drugs ◽  
Global Threat

Background: The emergence of infectious diseases and its resistance to approved drugs is a global threat to human health. The incidence of infectious diseases is increasing day by day and expected to rise exponentially in next 2 decades. Thus, there is a need for new treatment modalities for the treatment of microbial infections. Methods: Thus, in the current investigation, we have explored the existing drugs [metformin (Anti-diabetic), propranolol (Anti-hypertensive) and amitriptyline (antidepressant)] for treatment of infectious diseases. Results: An in-silico result of current investigation has shown the good interaction of metformin, propranolol, and amitriptyline towards various targets (Beta-lactamase, Penicillin-binding proteins, Staphylokinase protein, Oxidoreductase protein, etc.) of gram positive and gram negative bacteria as that of internal ligand. Further, in-vitro results have shown that the antibacterial activity of metformin, propranolol, and amitriptyline against Bacillus pumilus, Pseudomonas aeruginosa and Staphylococcus aureus. Conclusion: The parameters such as Microtiter assay: percentage growth retardation and bacterial growth kinetics, Minimum inhibitory concentration (MIC), Post-antibiotic assay and Biofilm formation have indicated the antibacterial potential of metformin, propranolol, and amitriptyline. However, before starting a clinical trial, complete safety and efficacy profile of drugs in the treatment of infectious diseases should be investigated.

scholarly journals APPLICATION OF NANOSTRUCTURES IN ANTIMICROBIAL THERAPY

2018 ◽  
Vol 10 (4) ◽  
pp. 11 ◽  
Author(s):  
Joshi Mahavir ◽  
Lata Sneh ◽  
Kanwar Preeti ◽  
Mishra Tulika
Keyword(s):  
Side Effects ◽  
Antimicrobial Agents ◽  
Polymeric Nanoparticles ◽  
Metal Oxide Nanoparticles ◽  
Cost Effective ◽  
Therapeutic Index ◽  
New Drugs ◽  
Multiple Drug ◽  
Great Success ◽  
Cell Wall Disruption

There are many infectious diseases that may be biofilm mediated, medical device-mediated or from some other agent, are now becoming life-threatening. Despite of availability of many antimicrobial agents, new drugs or therapeutics, these infections have continued to be a global health challenge. Nowadays, conventional antimicrobial agents have failed against many infections due to the emergence of multiple drug-resistant strains. Even, if there is a therapeutic efficacy of these drugs, there inappropriate amounts are resulting in an adequate therapeutic index, local and systematic side effects, including irritation, reduction in gut flora and other manifestations. To overcome such situations, nanostructures have exclusive physicochemical properties as they are ultra small, their size can be controlled, greater surface area to mass ratio, high reactivity and functionalizable structure. Encapsulation of antimicrobial drugs in these nanoparticle systems helps in reducing many side effects. It also helps in the sustained release of drug for a larger time period. Several metal and metal oxide nanoparticles such as silver, gold, zinc, etc. have shown a promising antimicrobial activity. Liposomes, polymeric nanoparticles, dendrimers, and solid lipid nanoparticles have achieved great success as efficient antimicrobial drug delivery systems. These nanoparticles use multiple biological pathways to exert their antimicrobial mechanism such as cell wall disruption, inhibition of RNA synthesis, protein synthesis, etc. Moreover,these preparations of nanoparticles are more cost-effective than that of antibiotic synthesis with lesser or no side effects.

Recent Advances in Drug Repurposing for Parkinson’s Disease

2019 ◽  
Vol 26 (28) ◽  
pp. 5340-5362 ◽  
Author(s):  
Xin Chen ◽  
Giuseppe Gumina ◽  
Kristopher G. Virga
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Drug Discovery ◽  
De Novo ◽  
Drug Repositioning ◽  
Drug Repurposing ◽  
Cost Effective ◽  
New Drugs ◽  
Recent Advances ◽  
Clinical Drugs

:As a long-term degenerative disorder of the central nervous system that mostly affects older people, Parkinson’s disease is a growing health threat to our ever-aging population. Despite remarkable advances in our understanding of this disease, all therapeutics currently available only act to improve symptoms but cannot stop the disease progression. Therefore, it is essential that more effective drug discovery methods and approaches are developed, validated, and used for the discovery of disease-modifying treatments for Parkinson’s disease. Drug repurposing, also known as drug repositioning, or the process of finding new uses for existing or abandoned pharmaceuticals, has been recognized as a cost-effective and timeefficient way to develop new drugs, being equally promising as de novo drug discovery in the field of neurodegeneration and, more specifically for Parkinson’s disease. The availability of several established libraries of clinical drugs and fast evolvement in disease biology, genomics and bioinformatics has stimulated the momentums of both in silico and activity-based drug repurposing. With the successful clinical introduction of several repurposed drugs for Parkinson’s disease, drug repurposing has now become a robust alternative approach to the discovery and development of novel drugs for this disease. In this review, recent advances in drug repurposing for Parkinson’s disease will be discussed.

Antimicrobial properties of actively purified secondary metabolites isolated from different marine organisms

2020 ◽  
Vol 21 ◽  
Author(s):  
Nilushi Indika Bamunu Arachchige ◽  
Fazlurrahman Khan ◽  
Young-Mog Kim
Keyword(s):  
Secondary Metabolites ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Antimicrobial Properties ◽  
Antimicrobial Effect ◽  
Cost Effective ◽  
Resistance Mechanisms ◽  
Marine Organisms ◽  
Antimicrobial Compounds

Background: The treatment of infection caused by pathogenic bacteria becomes one of the serious concerns globally. The failure in the treatment was found due to the exhibition of multiple resistance mechanisms against the antimicrobial agents. Emergence of resistant bacterial species has also been observed due to prolong treatment using conventional antibiotics. To combat these problems, several alternative strategies have been employed using biological and chemically synthesized compounds as antibacterial agents. Marine organisms considered as one of the potential sources for the isolation of bioactive compounds due to the easily available, cost-effective, and eco-friendly. Methods: The online search methodology was adapted for the collection of information related to the antimicrobial properties of marine-derived compounds. These compound has been isolated and purified by different purification techniques, and their structure also characterized. Furthermore, the antibacterial activities have been reported by using broth microdilution as well as disc diffusion assays. Results: The present review paper describes the antimicrobial effect of diverse secondary metabolites which are isolated and purified from the different marine organisms. The structural elucidation of each secondary metabolite has also been done in the present paper, which will help for the in silico designing of the novel and potent antimicrobial compounds. Conclusion: A thorough literature search has been made and summarizes the list of antimicrobial compounds that are isolated from both prokaryotic and eukaryotic marine organisms. The information obtained from the present paper will be helpful for the application of marine compounds as antimicrobial agents against different antibiotic-resistant human pathogenic bacteria.

Sign in / Sign up

Export Citation Format

Share Document