scholarly journals Microorganisms as a Potential Source of Molecules to Control Trypanosomatid Diseases

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1388
Author(s):  
Manuel Jesús Chan-Bacab ◽  
María Manuela Reyes-Estebanez ◽  
Juan Carlos Camacho-Chab ◽  
Benjamín Otto Ortega-Morales
Keyword(s):  
Heterotrophic Bacteria ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Future Research ◽  
Fungal Metabolites ◽  
Lead Compounds ◽  
Current State ◽  
Causative Agents ◽  
Antiparasitic Drugs ◽  
New Generation

Trypanosomatids are the causative agents of leishmaniasis and trypanosomiasis, which affect about 20 million people in the world’s poorest countries, leading to 95,000 deaths per year. They are often associated with malnutrition, weak immune systems, low quality housing, and population migration. They are generally recognized as neglected tropical diseases. New drugs against these parasitic protozoa are urgently needed to counteract drug resistance, toxicity, and the high cost of commercially available drugs. Microbial bioprospecting for new molecules may play a crucial role in developing a new generation of antiparasitic drugs. This article reviews the current state of the available literature on chemically defined metabolites of microbial origin that have demonstrated antitrypanosomatid activity. In this review, bacterial and fungal metabolites are presented; they originate from a range of microorganisms, including cyanobacteria, heterotrophic bacteria, and filamentous fungi. We hope to provide a useful overview for future research to identify hits that may become the lead compounds needed to accelerate the discovery of new drugs against trypanosomatids.

scholarly journals The Dialogue of the Host-Parasite Relationship:Leishmaniaspp. andTrypanosoma cruziInfection

2015 ◽  
Vol 2015 ◽  
pp. 1-19 ◽  
Author(s):  
Carlos Gustavo Vieira de Morais ◽  
Ana Karina Castro Lima ◽  
Rodrigo Terra ◽  
Rosiane Freire dos Santos ◽  
Silvia Amaral Gonçalves Da-Silva ◽  
...  
Keyword(s):  
Immune Response ◽  
Trypanosoma Cruzi ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Host Cells ◽  
Protective Response ◽  
Limited Efficacy ◽  
Causative Agents ◽  
Host Parasite ◽  
Emergence Of Resistance

The intracellular protozoaLeishmaniaspp. andTrypanosoma cruziand the causative agents of Leishmaniasis and Chagas disease, respectively, belong to the Trypanosomatidae family. Together, these two neglected tropical diseases affect approximately 25 million people worldwide. Whether the host can control the infection or develops disease depends on the complex interaction between parasite and host. Parasite surface and secreted molecules are involved in triggering specific signaling pathways essential for parasite entry and intracellular survival. The recognition of the parasite antigens by host immune cells generates a specific immune response.Leishmaniaspp. andT. cruzihave a multifaceted repertoire of strategies to evade or subvert the immune system by interfering with a range of signal transduction pathways in host cells, which causes the inhibition of the protective response and contributes to their persistence in the host. The current therapeutic strategies in leishmaniasis and trypanosomiasis are very limited. Efficacy is variable, toxicity is high, and the emergence of resistance is increasingly common. In this review, we discuss the molecular basis of the host-parasite interaction ofLeishmaniaandTrypanosoma cruziinfection and their mechanisms of subverting the immune response and how this knowledge can be used as a tool for the development of new drugs.

scholarly journals Extreme Fast Charging Technology—Prospects to Enhance Sustainable Electric Transportation

Energies ◽  
2019 ◽  
Vol 12 (19) ◽  
pp. 3721 ◽  
Author(s):  
Deepak Ronanki ◽  
Apoorva Kelkar ◽  
Sheldon S. Williamson
Keyword(s):  
Electric Vehicles ◽  
State Of The Art ◽  
Future Research ◽  
Solid State Transformer ◽  
Research Attention ◽  
Charging Infrastructure ◽  
Medium Voltage ◽  
Current State ◽  
Fast Charging ◽  
New Generation

With the growing fleet of a new generation electric vehicles (EVs), it is essential to develop an adequate high power charging infrastructure that can mimic conventional gasoline fuel stations. Therefore, much research attention must be focused on the development of off-board DC fast chargers which can quickly replenish the charge in an EV battery. However, use of the service transformer in the existing fast charging architecture adds to the system cost, size and complicates the installation process while directly connected to medium-voltage (MV) line. With continual improvements in power electronics and magnetics, solid state transformer (SST) technology can be adopted to enhance power density and efficiency of the system. This paper aims to review the current state of the art architectures and challenges of fast charging infrastructure using SST technology while directly connected to the MV line. Finally, this paper discusses technical considerations, challenges and introduces future research possibilities.

scholarly journals Bisphosphonate-Based Molecules as Potential New Antiparasitic Drugs

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2602 ◽  
Author(s):  
Joice Castelo Branco Santos ◽  
Jonathas Alves de Melo ◽  
Sweta Maheshwari ◽  
Wendy Marina Toscano Queiroz de Medeiros ◽  
Johny Wysllas de Freitas Oliveira ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Mevalonate Pathway ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Synthesis Process ◽  
Antiparasitic Activity ◽  
The World ◽  
Leishmania Spp ◽  
Antiparasitic Drugs ◽  
Antiparasitic Agents

Neglected tropical diseases such as Chagas disease and leishmaniasis affect millions of people around the world. Both diseases affect various parts of the globe and drugs traditionally used in therapy against these diseases have limitations, especially with regard to low efficacy and high toxicity. In this context, the class of bisphosphonate-based compounds has made significant advances regarding the chemical synthesis process as well as the pharmacological properties attributed to these compounds. Among this spectrum of pharmacological activity, bisphosphonate compounds with antiparasitic activity stand out, especially in the treatment of Chagas disease and leishmaniasis caused by Trypanosoma cruzi and Leishmania spp., respectively. Some bisphosphonate compounds can inhibit the mevalonate pathway, an essential metabolic pathway, by interfering with the synthesis of ergosterol, a sterol responsible for the growth and viability of these parasites. Therefore, this review aims to present the information about the importance of these compounds as antiparasitic agents and as potential new drugs to treat Chagas disease and leishmaniasis.

Ethnomedicinal, phytochemical and pharmacological profile of a mangrove plant Ceriops Decandra GriffDin Hou.

2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Imran Mahmud ◽  
Naznin Shahria ◽  
Sabina Yeasmin ◽  
Asif Iqbal ◽  
Emdadul Hasan Mukul ◽  
...  
Keyword(s):  
New Drugs ◽  
Future Research ◽  
Gastrointestinal Disorders ◽  
Pharmacological Profile ◽  
Mangrove Plant ◽  
Lead Compounds ◽  
Mangrove Tree ◽  
Pharmacological Significance ◽  
Ceriops Decandra ◽  
Different Parts

Abstract Ceriops decandra is a mangrove tree species, reputed for its folkloric uses in the treatment of gastrointestinal disorders, infection, snakebites, inflammation, and cancer. Different parts of the plant are rich with various phytoconstituents which include diterpenoids (ceriopsin A-G), triterpenoids (lupeol, α-amyrin, oleanolic acid, ursolic acid), and phenolics (catechin, procyanidins).These phytoconstituents and their derivatives could form a new basis for developing new drugs against various diseases. The objective of the present study is to compile the phytochemical, ethnobotanical, biological, and pharmacological significance of the plant to provide directions for future research to find out therapeutically active lead compounds for developing new drugs against diseases of current interest including diabetes, inflammation, and cancer.

scholarly journals Lipid and fatty acid metabolism in trypanosomatids

2021 ◽  
Vol 8 (11) ◽  
pp. 262-275
Author(s):  
Giovana Parreira de Aquino ◽  
Marco Antonio Mendes Gomes ◽  
Roberto Köpke Salinas ◽  
Maria Fernanda Laranjeira-Silva
Keyword(s):  
De Novo ◽  
Neglected Tropical Diseases ◽  
Treatment Options ◽  
Life Cycles ◽  
Protozoan Parasites ◽  
Life Cycle Stages ◽  
Leishmania Spp ◽  
Causative Agents ◽  
Major Energy Source ◽  
Antiparasitic Drugs

Trypanosomiases and leishmaniases are neglected tropical diseases that have been spreading to previously non-affected areas in recent years. Identification of new chemotherapeutics is needed as there are no vaccines and the currently available treatment options are highly toxic and often ineffective. The causative agents for these diseases are the protozoan parasites of the Trypanosomatidae family, and they alternate between invertebrate and vertebrate hosts during their life cycles. Hence, these parasites must be able to adapt to different environments and compete with their hosts for several essential compounds, such as amino acids, vitamins, ions, carbohydrates, and lipids. Among these nutrients, lipids and fatty acids (FAs) are essential for parasite survival. Trypanosomatids require massive amounts of FAs, and they can either synthesize FAs de novo or scavenge them from the host. Moreover, FAs are the major energy source during specific life cycle stages of T. brucei, T. cruzi, and Leishmania. Therefore, considering the distinctive features of FAs metabolism in trypanosomatids, these pathways could be exploited for the development of novel antiparasitic drugs. In this review, we highlight specific aspects of lipid and FA metabolism in the protozoan parasites T. brucei, T. cruzi, and Leishmania spp., as well as the pathways that have been explored for the development of new chemotherapies.

Self-leadership Training Review

2019 ◽  
Author(s):  
Andrew Sidwell ◽  
Michael Perry
Keyword(s):  
Leadership Training ◽  
Future Research ◽  
Training Methods ◽  
Current State ◽  
A Current

The purpose of this article was to examine the current state of self-leadership training. The authors analyzed all published, publicly available studies (in English) pertaining to self-leadership training methods, offering a current state of self-leadership training, and implications for future research.

The Role of nitro (NO2-), chloro (Cl), and fluoro (F) Substitution in the Design of Antileishmanial and Antichagasic Compounds

2020 ◽  
Vol 21 ◽  
Author(s):  
Boniface Pone ◽  
Ferreira Igne Elizabeth
Keyword(s):  
Chagas Disease ◽  
Mammalian Cells ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
Pharmacokinetic Studies ◽  
Scientific Publications ◽  
Antitrypanosomal Activity ◽  
Chemical Groups

: Neglected tropical diseases (NTDs) are responsible for over 500,000 deaths annually and are characterized by multiple disabilities. Leishmaniasis and Chagas disease are among the most severe NTDs, and are caused by the Leishmania sp, and Trypanosoma cruzi, respectively. Glucantime, pentamidine and miltefosine are commonly used to treat leishmaniasis, whereas nifurtimox, benznidazole are current treatments for Chagas disease. However, these treatments are associated with drug resistance, and severe side effects. Hence, the development of synthetic products, especially those containing N02, F, or Cl, which chemical groups are known to improve the biological activity. The present work summarizes the information on the antileishmanial and antitrypanosomal activity of nitro-, chloro-, and fluoro-synthetic derivatives. Scientific publications referring to halogenated derivatives in relation to antileishmanial and antitrypanosomal activities were hand searched in databases such as SciFinder, Wiley, Science Direct, PubMed, ACS, Springer, Scielo, and so on. According to the literature information, more than 90 compounds were predicted as lead molecules with reference to their IC50/EC50 values in in vitro studies. It is worth to mention that only active compounds with known cytotoxic effects against mammalian cells were considered in the present study. The observed activity was attributed to the presence of nitro-, fluoro- and chloro-groups in the compound backbone. All in all, nitro and h0alogenated derivatives are active antileishmanial and antitrypanosomal compounds and can serve as baseline for the development of new drugs against leishmaniasis and Chagas disease. However, efforts on in vitro and in vivo toxicity studies of the active synthetic compounds is still needed. Pharmacokinetic studies, and the mechanism of action of the promising compounds need to be explored. The use of new catalysts and chemical transformation can afford unexplored halogenated compounds with improved antileishmanial and antitrypanosomal activity.

Antimicrobial Peptides and their Multiple Effects at Sub-Inhibitory Concentrations

2020 ◽  
Vol 20 (14) ◽  
pp. 1264-1273 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Walter Verrusio ◽  
Mauro Cacciafesta ◽  
Maria Luisa Mangoni
Keyword(s):  
Antimicrobial Peptides ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Lead Compounds ◽  
Bacterial Pathogenicity ◽  
Growth Inhibitory ◽  
Resistant Strains ◽  
Conventional Antibiotics

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.

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