scholarly journals Cutaneous Leishmaniasis: Treatment Options and Possibilities for Drug Repurposing

2019 ◽  
Vol 2 (1) ◽  
pp. 9-19
Author(s):  
Aziz Alsohaimi
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Amphotericin B ◽  
Treatment Options ◽  
Geographic Location ◽  
Drug Repurposing ◽  
Current Treatment ◽  
Obligate Intracellular ◽  
Mucocutaneous Leishmaniasis ◽  
High Degree ◽  
Genus Leishmania

Leishmaniasis is a tropical disease caused by aprotozoan which is obligate intracellular parasite belongs to the genus Leishmania. There are 3 forms of the disease: visceral leishmaniasis, cutaneous leishmaniasis which is the most common, and mucocutaneous leishmaniasis. The most important compounds used to treat leishmaniasis were meglumine antimoniate (e.g. glucantime), sodium stibogluconate (e.g. pentostam) and pentavalent antimonials. There are other drugs that may be used such as pentamidine and amphotericin B. Until now, the pentavalent antimonial compounds remain the corner stone in the treatment of cutaneous leishmaniasis although this group possesses high degree of toxicity. Other treatment options include the pentamidines and liposomal amphotericin B (AmBisome). Combination therapies using AmBisome and miltefosine are another effective alternative to antimonial compounds. Other latest therapeutic options include photodynamic therapy, tamoxifen and imiquimod. The proper choice of antileishmanial therapy depends on the geographic location, host immune status, availability of the drug, and expertise of the treating physician. The present review summarizes the current treatment options available for cutaneous leishmaniasis as well as some drugs on the horizon that show promising results in the treatment of cutaneous leishmaniasis.

scholarly journals Identification of Antifungal Compounds against Multidrug Resistant Candida auris Utilizing a High Throughput Drug Repurposing Screen

2021 ◽  
Author(s):  
Yu-Shan Cheng ◽  
Jose Santinni Roma ◽  
Min Shen ◽  
Caroline Mota Fernandes ◽  
Patricia S. Tsang ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Multidrug Resistant ◽  
Current Treatment ◽  
Drug Combinations ◽  
Serine Palmitoyltransferase ◽  
Candida Auris ◽  
Pharmacologically Active

Candida auris is an emerging fatal fungal infection that has resulted in several outbreaks in hospitals and care facilities. Current treatment options are limited by the development of drug resistance. Identifying new pharmaceuticals to combat these drug-resistant infections will thus be required to overcome this unmet medical need. We have established a bioluminescent ATP-based assay to identify new compounds and potential drug combinations showing effective growth inhibition against multiple strains of multidrug resistant Candida auris. The assay is robust and suitable for assessing large compound collections by high throughput screening. Utilizing this assay, we conducted a screen of 4,314 approved drugs and pharmacologically active compounds which yielded 25 compounds including 6 novel anti-Candida auris compounds and 13 sets of potential two drug combinations. Among the drug combinations, the serine palmitoyltransferase inhibitor myriocin demonstrated a combinational effect with flucytosine against all tested isolates during screening. This combinational effect was confirmed in 13 clinical isolates of Candida auris.

scholarly journals Identification of 37 Heterogeneous Drug Candidates for Treatment of COVID-19 via a Rational Transcriptomics-Based Drug Repurposing Approach

2021 ◽  
Vol 14 (2) ◽  
pp. 87
Author(s):  
Andrea Gelemanović ◽  
Tinka Vidović ◽  
Višnja Stepanić ◽  
Katarina Trajković
Keyword(s):  
Treatment Options ◽  
Drug Repurposing ◽  
Enrichment Analysis ◽  
Current Treatment ◽  
Host Cells ◽  
Biological Knowledge ◽  
Pathway Enrichment Analysis ◽  
Biological Processes ◽  
Pathway Enrichment ◽  
Drug Candidates

A year after the initial outbreak, the COVID-19 pandemic caused by SARS-CoV-2 virus remains a serious threat to global health, while current treatment options are insufficient to bring major improvements. The aim of this study is to identify repurposable drug candidates with a potential to reverse transcriptomic alterations in the host cells infected by SARS-CoV-2. We have developed a rational computational pipeline to filter publicly available transcriptomic datasets of SARS-CoV-2-infected biosamples based on their responsiveness to the virus, to generate a list of relevant differentially expressed genes, and to identify drug candidates for repurposing using LINCS connectivity map. Pathway enrichment analysis was performed to place the results into biological context. We identified 37 structurally heterogeneous drug candidates and revealed several biological processes as druggable pathways. These pathways include metabolic and biosynthetic processes, cellular developmental processes, immune response and signaling pathways, with steroid metabolic process being targeted by half of the drug candidates. The pipeline developed in this study integrates biological knowledge with rational study design and can be adapted for future more comprehensive studies. Our findings support further investigations of some drugs currently in clinical trials, such as itraconazole and imatinib, and suggest 31 previously unexplored drugs as treatment options for COVID-19.

N-acetylcysteine reduces amphotericin B deoxycholate nephrotoxicity and improves the outcome of murine cryptococcosis

2020 ◽  
Vol 58 (6) ◽  
pp. 835-844 ◽  
Author(s):  
Thais Furtado Ferreira Magalhães ◽  
Marliete Carvalho Costa ◽  
Rodrigo Assunção Holanda ◽  
Gabriela Freitas Ferreira ◽  
Vanessa Silva Dutra Carvalho ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Fungal Growth ◽  
Drug Repurposing ◽  
Current Treatment ◽  
Yeast Cells ◽  
Therapeutic Effects ◽  
Post Inoculation ◽  
Interesting Approach ◽  
Life Threatening ◽  
Oxidative Effects

Abstract Cryptococcosis is a life-threatening fungal infection, and its current treatment is toxic and subject to resistance. Drug repurposing represents an interesting approach to find drugs to reduce the toxicity of antifungals. In this study, we evaluated the combination of N-acetylcysteine (NAC) with amphotericin B (AMB) for the treatment of cryptococcosis. We examined the effects of NAC on fungal morphophysiology and on the macrophage fungicidal activity 3 and 24 hours post inoculation. The therapeutic effects of NAC combination with AMB were investigated in a murine model with daily treatments regimens. NAC alone reduced the oxidative burst generated by AMB in yeast cells, but did not inhibit fungal growth. The combination NAC + AMB decreased capsule size, zeta potential, superoxide dismutase activity and lipid peroxidation. In macrophage assays, NAC + AMB did not influence the phagocytosis, but induced fungal killing with different levels of oxidative bursts when compared to AMB alone: there was an increased reactive oxygen species (ROS) after 3 hours and reduced levels after 24 hours. By contrast, ROS remained elevated when AMB was tested alone, demonstrating that NAC reduced AMB oxidative effects without influencing its antifungal activity. Uninfected mice treated with NAC + AMB had lower concentrations of serum creatinine and glutamate-pyruvate transaminase in comparison to AMB. The combination of NAC + AMB was far better than AMB alone in increasing survival and reducing morbidity in murine-induced cryptococcosis, leading to reduced fungal burden in lungs and brain and also lower concentrations of pro-inflammatory cytokines in the lungs. In conclusion, NAC + AMB may represent an alternative adjuvant for the treatment of cryptococcosis.

scholarly journals In silico drug repurposing for filarial infection predicts nilotinib and paritaprevir as potential inhibitors of the Wolbachia 5′-aminolevulinic acid synthase

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexander Kwarteng ◽  
Ebenezer Asiedu ◽  
Augustina Sylverken ◽  
Amma Larbi ◽  
Yusif Mubarik ◽  
...  
Keyword(s):  
In Silico ◽  
Aminolevulinic Acid ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Clinical Effectiveness ◽  
Current Treatment ◽  
Binding Affinities ◽  
Active Site Residues ◽  
Experimental Validations ◽  
Potential Inhibitors

AbstractFilarial infections affect millions of individuals and are responsible for some notorious disabilities. Current treatment options involve repeated mass drug administrations, which have been met with several challenges despite some successes. Administration of doxycycline, an anti-Wolbachia agent, has shown clinical effectiveness but has several limitations, including long treatment durations and contraindications. We describe the use of an in silico drug repurposing approach to screening a library of over 3200 FDA-approved medications against the filarial endosymbiont, Wolbachia. We target the enzyme which catalyzes the first step of heme biosynthesis in the Wolbachia. This presents an opportunity to inhibit heme synthesis, which leads to depriving the filarial worm of heme, resulting in a subsequent macrofilaricidal effect. High throughput virtual screening, molecular docking and molecular simulations with binding energy calculations led to the identification of paritaprevir and nilotinib as potential anti-Wolbachia agents. Having higher binding affinities to the catalytic pocket than the natural substrate, these drugs have the structural potential to bind and engage active site residues of the wolbachia 5′-Aminolevulinic Acid Synthase. We hereby propose paritaprevir and nilotinib for experimental validations as anti-Wolbachia agents.

scholarly journals Promising Drug Targets and Compounds with Anti-Toxoplasma gondii Activity

2021 ◽  
Vol 9 (9) ◽  
pp. 1960
Author(s):  
Marco Silva ◽  
Cátia Teixeira ◽  
Paula Gomes ◽  
Margarida Borges
Keyword(s):  
Drug Discovery ◽  
Toxoplasma Gondii ◽  
Drug Targets ◽  
Treatment Options ◽  
Drug Repurposing ◽  
Protozoan Parasite ◽  
Acid Synthesis ◽  
Current Treatment ◽  
Future Research ◽  
World Population

Toxoplasmosis is a parasitic disease caused by the globally distributed protozoan parasite Toxoplasma gondii, which infects around one-third of the world population. This disease may result in serious complications for fetuses, newborns, and immunocompromised individuals. Current treatment options are old, limited, and possess toxic side effects. Long treatment durations are required since the current therapeutic system lacks efficiency against T. gondii tissue cysts, promoting the establishment of latent infection. This review highlights the most promising drug targets involved in anti-T. gondii drug discovery, including the mitochondrial electron transport chain, microneme secretion pathway, type II fatty acid synthesis, DNA synthesis and replication and, DNA expression as well as others. A description of some of the most promising compounds demonstrating antiparasitic activity, developed over the last decade through drug discovery and drug repurposing, is provided as a means of giving new perspectives for future research in this field.

scholarly journals The Future Perspectives of Drug Repurposing and Treatment for the Drug Resistant Breast Cancer: A Review

2021 ◽  
Author(s):  
Panneerselvam Theivendren ◽  
Selvaraj Kunjiappan ◽  
Yashoda Mariappa Hegde ◽  
Kaveena Ravi ◽  
Sivakumar Vellaichamy ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Survival Rates ◽  
Drug Repurposing ◽  
Current Treatment ◽  
New Drugs ◽  
Health Concern ◽  
Drug Resistant ◽  
The Future ◽  
New Treatment

Breast cancer is a major health concern as it is the second leading cause of death from cancer. There are several well-known risk factors that contribute to breast cancer. Despite the various treatment options available, complete cure is still difficult due to heterogenicity of BC subtypes. As a result, identifying BC subtypes is critical for determining the optimal treatment approach. Over the last several years, new drugs targeting particular therapeutic targets have resulted in significant advances in the treatment of breast cancer. Nonetheless, resistance to treatment is the “major” issue, and a significant increase in survival rates has been the main focus for researchers. The purpose of this review article is to provide a broad overview of the molecular basis of drug resistance in breast cancer, as well as a detailed assessment of current treatment options, potential new treatment methods for drug-resistant breast cancer and repurposed drugs used for treatment. The possibility of non-cancer drugs being studied for breast cancer in the future, as well as the obstacles and bottlenecks of drug repurposing, is also highlighted. Finally, we go through present problems and future prospects in drug-resistant breast cancer therapy.

An Overview of Dementias

2012 ◽  
Vol 21 (3) ◽  
pp. 75-84
Author(s):  
Venkata Vijaya K. Dalai ◽  
Jason E. Childress ◽  
Paul E Schulz
Keyword(s):  
Clinical Presentation ◽  
Treatment Options ◽  
Current Treatment ◽  
Great Variability ◽  
Health Concern ◽  
Public Health Concern ◽  
Life Threatening ◽  
The Common ◽  
Neurodegenerative Dementias ◽  
Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

Initiation of Clozapine Therapy in a Patient With Preexisting Leukopenia: A Discussion of the Rationale of Current Treatment Options

2001 ◽  
Vol 13 (4) ◽  
pp. 233-237 ◽  
Author(s):  
Roger Boshes ◽  
Theo Manschreck ◽  
Jean Desrosiers ◽  
Steven Candela ◽  
Meredith Hanrahan-Boshes
Keyword(s):  
Treatment Options ◽  
Current Treatment ◽  
Clozapine Therapy

Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature

2019 ◽  
Vol 20 (10) ◽  
pp. 1008-1017 ◽  
Author(s):  
Vandita Kakkar ◽  
Manoj Kumar Verma ◽  
Komal Saini ◽  
Indu Pal Kaur
Keyword(s):  
Drug Delivery ◽  
Oral Cancer ◽  
Treatment Options ◽  
Oral Submucous Fibrosis ◽  
Survival Rates ◽  
Cancer Therapeutics ◽  
Developed Countries ◽  
Current Treatment ◽  
Poor Overall Survival ◽  
Hereditary Disorders

Oral Cancer (OC) is a serious and growing problem which constitutes a huge burden on people in more and less economically developed countries alike. The scenario is clearly depicted from the increase in the expected number of new cases in the US diagnosed with OC from 49,670 people in 2016, to 49,750 cases in 2017. The situation is even more alarming in India, with 75,000 to 80,000 new cases being reported every year, thus making it the OC capital of the world. Leukoplakia, erythroplakia, oral lichen planus, oral submucous fibrosis, discoid lupus erythmatosus, hereditary disorders such as dyskeratosis congenital and epidermolisys bullosa are highlighted by WHO expert working group as the predisposing factors increasing the risk of OC. Consumption of tobacco and alcohol, genetic factors, and human papilloma virus are assigned as the factors contributing to the aetiology of OC. On the other hand, pathogenesis of OC involves not only apoptosis but also pain, inflammation and oxidative stress. Inspite of current treatment options (surgery, radiotherapy, and chemotherapy), OC is often associated with recurrence and formation of secondary primary tumours resulting in poor overall survival rates (∼50%). The intervention of nano technology-based drug delivery systems as therapeutics for cancers is often viewed as a cutting edge for technologists. Though ample literature on the usefulness of nano-coutured cancer therapeutics, rarely any product is in pipeline. Yet, despite all the hype about nanotechnology, there are few ongoing trials. This review discusses the current and future trends of nano-based drug delivery for the treatment of OC.

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