Novel Treatments against Mycobacterium tuberculosis Based on Drug Repurposing

Mourenza, Álvaro; Gil, José A.; Mateos, Luís M.; Letek, Michal

doi:10.3390/antibiotics9090550

Cited by 23 publications

(14 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, resistance to pyrazinamide in this pathogen is due to mutations in the gene encoding pyrazinamidase (Tahir et al 2020 ). Latest developments in tuberculosis antimicrobial agents include avermectins and fluvastatin Mourenza et al ( 2020 ). Avermectins are highly active anthelmintic macrolides against MDR strains of clinical isolates of M. tuberculosis.…”

Section: The Need For New Secondary Metabolitesmentioning

confidence: 99%

Impact of novel microbial secondary metabolites on the pharma industry

Ramírez-Rendon

Passari

Ruíz-Villafán

et al. 2022

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

Microorganisms are remarkable producers of a wide diversity of natural products that significantly improve human health and well-being. Currently, these natural products comprise half of all the pharmaceuticals on the market. After the discovery of penicillin by Alexander Fleming 85 years ago, the search for and study of antibiotics began to gain relevance as drugs. Since then, antibiotics have played a valuable role in treating infectious diseases and have saved many human lives. New molecules with anticancer, hypocholesterolemic, and immunosuppressive activity have now been introduced to treat other relevant diseases. Smaller biotechnology companies and academic laboratories generate novel antibiotics and other secondary metabolites that big pharmaceutical companies no longer develop. The purpose of this review is to illustrate some of the recent developments and to show the potential that some modern technologies like metagenomics and genome mining offer for the discovery and development of new molecules, with different functions like therapeutic alternatives needed to overcome current severe problems, such as the SARS-CoV-2 pandemic, antibiotic resistance, and other emerging diseases. Key points • Novel alternatives for the treatment of infections caused by bacteria, fungi, and viruses. • Second wave of efforts of microbial origin against SARS-CoV-2 and related variants.• Microbial drugs used in clinical practice as hypocholesterolemic agents, immunosuppressants, and anticancer therapy. Keywords Microbial natural products • Antibiotics • Hypocholesterolemics• Anticancer drugs • Immunosuppressants • Antibiotic resistance Abbreviations FDA Food and Drug Administration NA Not applicable cSSSI Complicated skin, and skin structure infections ABSSSIs Acute bacterial skin, and skin structure infections cUTI Complicated urinary tract infections cIAI Complicated intra-abdominal infections HABP/VABP Hospital-acquired bacterial pneumonia, and ventilator-associated bacterial pneumonia CABP Community-acquired bacterial pneumonia. Estimate of U.S. Sales for 2018 was based on data previously reported Carr and Stringer 2019 * Sergio Sánchez

show abstract

Section: The Need For New Secondary Metabolitesmentioning

confidence: 99%

Impact of novel microbial secondary metabolites on the pharma industry

Ramírez-Rendon

Passari

Ruíz-Villafán

et al. 2022

Appl Microbiol Biotechnol

View full text Add to dashboard Cite

show abstract

“…An additional benefit of drug repurposing is the potential to identify or validate vulnerable targets and/or pathways that can be exploited for further drug development [8][9][10]. Bortezomib is the first human proteasome inhibitor approved for the treatment of multiple myeloma and mantle cell lymphoma [48].…”

Section: Target-based Repurposingmentioning

confidence: 99%

“…It is also referred to as drug repositioning, redirecting, re-tasking, reprofiling or recycling [8,9]. This strategy offers several advantages over a conventional drug discovery approach, including (i) reduced risk of failure, (ii) quicker development times, (iii) less investment and lower average costs, and (iv) the possibility of identifying new targets and/or pathways for further investigation (Figure 2) [8][9][10]. Drug repurposing has been successfully applied to several diseases and conditions including HIV, cancer and arthritis [9].…”

Section: Introductionmentioning

confidence: 99%

Drug Repurposing for Tuberculosis

Cardoso¹,

Oosthuizen²,

Peton³

et al. 2022

Drug Repurposing - Molecular Aspects and Therapeutic Applications

View full text Add to dashboard Cite

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a major global health concern given the increase in multiple forms of drug-resistant TB. This underscores the importance of a continuous pipeline of new anti-TB agents. From recent studies, it is evident that the increase in drug efficacy is being achieved through re-engineering old TB-drug families and repurposing known drugs. This approach has led to producing a newer class of compounds which not only saves time and investment in developing newer drugs but is also effective in identifying drug candidates with novel mechanisms to treat multi-drug resistant strains. The repurposed drugs moxifloxacin, linezolid, and clofazimine are used to treat extensively drug-resistant TB when first- and/or second-line drugs fail. The chapter covers a detailed background on the current status of the repurposed drugs in the TB drug-discovery pipeline and discusses a potential way forward.

show abstract

“…TNF-α inhibitors and LT-α inhibitors, highly successful in cancer treatment, also show potential for repurposing, as an in vitro granuloma model reveals their ability to resuscitate dormant TB via controlled immunosuppression [ 64 ]. There is a recent burst of exploration into similar molecules, such as nilotinib, gefitinib and fostamatinib, each showing varied mechanisms of action, for example, enhancing autophagy [ 65 , 66 , 67 ].…”

Section: Repurposing Immunomodulatory Compoundsmentioning

confidence: 99%

The Prospect of Repurposing Immunomodulatory Drugs for Adjunctive Chemotherapy against Tuberculosis: A Critical Review

Lee

Bhakta

2021

Antibiotics

View full text Add to dashboard Cite

Tuberculosis (TB) remains a global health emergency, with an estimated 2 billion people infected across the world, and 1.4 million people dying to this disease every year. Many aspects of the causative agent, Mycobacterium tuberculosis, make this disease difficult for healthcare and laboratory researchers to fight against, such as unique pathophysiology, latent infection and long and complex treatment regimens, thus causing patient non-compliance with the treatment. Development of new drugs is critical for tackling these problems. Repurposing drugs is a promising strategy for generating an effective drug treatment whilst circumventing many of the challenges of conventional drug development. In this regard, the incorporation of immunomodulatory drugs into the standard regimen to potentiate frontline drugs is found to be highly appealing. Drugs of diverse chemical classes and drug categories are increasingly being evidenced to possess antitubercular activity, both in vitro and in vivo. This article explores and discusses the molecular entities that have shown promise in being repurposed for use in anti-TB adjunctive therapy and aims to provide the most up-to-date picture of their progress.

show abstract

Novel Treatments against Mycobacterium tuberculosis Based on Drug Repurposing

Cited by 23 publications

References 84 publications

Impact of novel microbial secondary metabolites on the pharma industry

Impact of novel microbial secondary metabolites on the pharma industry

Drug Repurposing for Tuberculosis

The Prospect of Repurposing Immunomodulatory Drugs for Adjunctive Chemotherapy against Tuberculosis: A Critical Review

Contact Info

Product

Resources

About