scholarly journals Cheaper faster drug development validated by the repositioning of drugs against neglected tropical diseases

2015 ◽  
Vol 12 (104) ◽  
pp. 20141289 ◽  
Author(s):  
Kevin Williams ◽  
Elizabeth Bilsland ◽  
Andrew Sparkes ◽  
Wayne Aubrey ◽  
Michael Young ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Boolean Functions ◽  
Neglected Tropical Diseases ◽  
Quantitative Structure Activity Relationship ◽  
New Drugs ◽  
Automation System ◽  
Tropical Diseases ◽  
Standard Drug ◽  
Anti Cancer ◽  
Lead Generation

There is an urgent need to make drug discovery cheaper and faster. This will enable the development of treatments for diseases currently neglected for economic reasons, such as tropical and orphan diseases, and generally increase the supply of new drugs. Here, we report the Robot Scientist ‘Eve’ designed to make drug discovery more economical. A Robot Scientist is a laboratory automation system that uses artificial intelligence (AI) techniques to discover scientific knowledge through cycles of experimentation. Eve integrates and automates library-screening, hit-confirmation, and lead generation through cycles of quantitative structure activity relationship learning and testing. Using econometric modelling we demonstrate that the use of AI to select compounds economically outperforms standard drug screening. For further efficiency Eve uses a standardized form of assay to compute Boolean functions of compound properties. These assays can be quickly and cheaply engineered using synthetic biology, enabling more targets to be assayed for a given budget. Eve has repositioned several drugs against specific targets in parasites that cause tropical diseases. One validated discovery is that the anti-cancer compound TNP-470 is a potent inhibitor of dihydrofolate reductase from the malaria-causing parasite Plasmodium vivax .

scholarly journals WIPO Re:Search: Catalyzing Public-Private Partnerships to Accelerate Tropical Disease Drug Discovery and Development

2019 ◽  
Vol 4 (1) ◽  
pp. 53 ◽  
Author(s):  
Cathyryne Manner ◽  
Katy Graef ◽  
Jennifer Dent
Keyword(s):  
Drug Discovery ◽  
Intellectual Property ◽  
Neglected Tropical Diseases ◽  
Tropical Disease ◽  
New Drugs ◽  
World Intellectual Property Organization ◽  
Tropical Diseases ◽  
Middle Income ◽  
Drug Discovery And Development ◽  
Partnership Model

Tropical diseases, including malaria and a group of infections termed neglected tropical diseases (NTDs), pose enormous threats to human health and wellbeing globally. In concert with efforts to broaden access to current treatments, it is also critical to expand research and development (R&D) of new drugs that address therapeutic gaps and concerns associated with existing medications, including emergence of resistance. Limited commercial incentives, particularly compared to products for diseases prevalent in high-income countries, have hindered many pharmaceutical companies from contributing their immense product development know-how and resources to tropical disease R&D. In this article we present WIPO Re:Search, an international initiative co-led by BIO Ventures for Global Health (BVGH) and the World Intellectual Property Organization (WIPO), as an innovative and impactful public-private partnership model that promotes cross-sector intellectual property sharing and R&D to accelerate tropical disease drug discovery and development. Importantly, WIPO Re:Search also drives progress toward the United Nations Sustainable Development Goals (SDGs). Through case studies, we illustrate how WIPO Re:Search empowers high-quality tropical disease drug discovery researchers from academic/non-profit organizations and small companies (including scientists in low- and middle-income countries) to leapfrog their R&D programs by accessing pharmaceutical industry resources that may not otherwise be available to them.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

scholarly journals Editorial: Cheminformatics Approaches in Drug Discovery for Neglected Tropical Diseases

2021 ◽  
Vol 9 ◽  
Author(s):  
Luciana Scotti ◽  
Eugene Muratov ◽  
Alejandro Speck-Planche ◽  
Marcus T. Scotti
Keyword(s):  
Drug Discovery ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases

scholarly journals High-Throughput Screening Platform for Natural Product–Based Drug Discovery Against 3 Neglected Tropical Diseases

2014 ◽  
Vol 20 (1) ◽  
pp. 82-91 ◽  
Author(s):  
F. Annang ◽  
G. Pérez-Moreno ◽  
R. García-Hernández ◽  
C. Cordon-Obras ◽  
J. Martín ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Natural Product ◽  
High Throughput ◽  
High Throughput Screening ◽  
Neglected Tropical Diseases ◽  
Chemical Diversity ◽  
Tropical Diseases ◽  
Isolation And Characterization ◽  
Microbial Extracts

African trypanosomiasis, leishmaniasis, and Chagas disease are 3 neglected tropical diseases for which current therapeutic interventions are inadequate or toxic. There is an urgent need to find new lead compounds against these diseases. Most drug discovery strategies rely on high-throughput screening (HTS) of synthetic chemical libraries using phenotypic and target-based approaches. Combinatorial chemistry libraries contain hundreds of thousands of compounds; however, they lack the structural diversity required to find entirely novel chemotypes. Natural products, in contrast, are a highly underexplored pool of unique chemical diversity that can serve as excellent templates for the synthesis of novel, biologically active molecules. We report here a validated HTS platform for the screening of microbial extracts against the 3 diseases. We have used this platform in a pilot project to screen a subset (5976) of microbial extracts from the MEDINA Natural Products library. Tandem liquid chromatography–mass spectrometry showed that 48 extracts contain potentially new compounds that are currently undergoing de-replication for future isolation and characterization. Known active components included actinomycin D, bafilomycin B1, chromomycin A3, echinomycin, hygrolidin, and nonactins, among others. The report here is, to our knowledge, the first HTS of microbial natural product extracts against the above-mentioned kinetoplastid parasites.

Two diseases, one approach: multitarget drug discovery in Alzheimer's and neglected tropical diseases

MedChemComm ◽  
2014 ◽  
Vol 5 (7) ◽  
pp. 853-861 ◽  
Author(s):  
F. Prati ◽  
E. Uliassi ◽  
M. L. Bolognesi
Keyword(s):  
Drug Discovery ◽  
Therapeutic Approach ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases ◽  
Promising Therapeutic Approach

Multitarget drug discovery may represent a promising therapeutic approach to treat Alzheimer's and neglected tropical diseases.

scholarly journals Neglected tropical diseases in Brazil

2009 ◽  
Vol 51 (5) ◽  
pp. 247-253 ◽  
Author(s):  
José Angelo L. Lindoso ◽  
Ana Angélica B.P. Lindoso
Keyword(s):  
Neglected Tropical Diseases ◽  
Clinical Manifestations ◽  
Northern Region ◽  
New Drugs ◽  
World Health ◽  
Tropical Diseases ◽  
The North ◽  
The World ◽  
The Status ◽  
Health Organization

Poverty is intrinsically related to the incidence of Neglected Tropical Diseases (NTDs). The main countries that have the lowest human development indices (HDI) and the highest burdens of NTDs are located in tropical and subtropical regions of the world. Among these countries is Brazil, which is ranked 70th in HDI. Nine out of the ten NTDs established by the World Health Organization (WHO) are present in Brazil. Leishmaniasis, tuberculosis, dengue fever and leprosy are present over almost the entire Brazilian territory. More than 90% of malaria cases occur in the Northern region of the country, and lymphatic filariasis and onchocerciasis occur in outbreaks in a particular region. The North and Northeast regions of Brazil have the lowest HDIs and the highest rates of NTDs. These diseases are considered neglected because there is not important investment in projects for the development of new drugs and vaccines and existing programs to control these diseases are not sufficient. Another problem related to NTDs is co-infection with HIV, which favors the occurrence of severe clinical manifestations and therapeutic failure. In this article, we describe the status of the main NTDs currently occurring in Brazil and relate them to the HDI and poverty.

Targeting pteridine reductase 1 and dihydrofolate reductase: the old is a new trend for leishmaniasis drug discovery

2019 ◽  
Vol 11 (16) ◽  
pp. 2107-2130 ◽  
Author(s):  
Gustavo Machado das Neves ◽  
Luciano P Kagami ◽  
Itamar L Gonçalves ◽  
Vera L Eifler-Lima
Keyword(s):  
Dihydrofolate Reductase ◽  
Drug Targets ◽  
Neglected Tropical Diseases ◽  
Molecular Targets ◽  
New Drugs ◽  
Tropical Diseases ◽  
The World ◽  
Leishmania Spp ◽  
Systemic Manifestations ◽  
Potential Drug Targets

Leishmaniasis is one of the major neglected tropical diseases in the world and it is considered endemic in 88 countries. This disease is transmitted by a Leishmania spp. infected sandfly and it may lead to cutaneous or systemic manifestations. The preconized treatment has low efficacy and there are cases of resistance to some drugs. Therefore, the search for new efficient molecular targets that can lead to the preparation of new drugs must be pursued. This review aims to evaluate both Leishmania enzymes PTR1 and DHFR-TS as potential drug targets, highlight their inhibitors and to discuss critically the use of chemoinformatics to elucidate interactions and propose new molecules against these enzymes.

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