Semisynthesis of new aphidicolin derivatives with high activity against Trypanosoma cruzi

Santos, Gabriela Bianchi dos; Krogh, Renata; Magalhães, Luma G.; Andricopulo, Adriano D.; Pupo, Mônica Tallarico; Emery, Flávio da Silva

doi:10.1016/j.bmcl.2016.01.033

Cited by 9 publications

(6 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Komaroviquinone was found to decrease the antibody production in T. cruzi (Uchiyama et al, 2005), while 5-epi-icetexone induced cell cycle arrest at S/G2 phases (Lozano et al, 2012a). A recent evidence suggests that an aphidicolin derivative has high potency and selectivity against parasitic amastigote cells in T. cruzi (Santos et al, 2016). However, serratol (Schmidt et al, 2011), hypoestenonols A/B (Al , and diterpenes from some Vietnamese corals (Thao et al, 2015) were found to act against Trypanosoma brucei).…”

Section: Resultsmentioning

confidence: 99%

Diterpenes as lead molecules against neglected tropical diseases

et al. 2016

View full text Add to dashboard Cite

Nowadays, neglected tropical diseases (NTDs) are reported to be present everywhere. Poor and developing areas in the world have received great attention to NTDs. Drug resistance, safety profile, and various challenges stimulate the search for alternative medications. Plant-based drugs are viewed with great interest, as they are believed to be devoid of side effects. Diterpenes, a family of essential oils, have showed attractive biological effects. A systematic review of the literature was carried out to summarize available evidences of diterpenes against NTDs. For this, databases were searched using specific search terms. Among the 2338 collected reports, a total of 181 articles were included in this review. Of them, 148 dealt with investigations using single organisms, and 33 used multiple organisms. No mechanisms of action were reported in the case of 164 reports. A total of 93.92% were related to nonclinical studies, and 4.42% and 1.66% dealt with preclinical and clinical studies, respectively. The review displays that many diterpenes are effective upon Chagas disease, chikungunya, echinococcosis, dengue, leishmaniasis, leprosy, lymphatic filariasis, malaria, schistosomiasis, and tuberculosis. Indeed, diterpenes are amazing drug candidates against NTDs. Copyright © 2016 John Wiley & Sons, Ltd.

show abstract

Section: Resultsmentioning

confidence: 99%

Diterpenes as lead molecules against neglected tropical diseases

et al. 2016

View full text Add to dashboard Cite

show abstract

“…APH is metabolised by cytochrome P-450 dependent degradation [220]. APH and its derivatives are considered as potential therapeutics for parasitic diseases, e.g., Chagas disease [221]. …”

Section: Compoundsmentioning

confidence: 99%

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

et al. 2017

View full text Add to dashboard Cite

DNA replication is a highly demanding process regarding the energy and material supply and must be precisely regulated, involving multiple cellular feedbacks. The slowing down or stalling of DNA synthesis and/or replication forks is referred to as replication stress (RS). Owing to the complexity and requirements of replication, a plethora of factors may interfere and challenge the genome stability, cell survival or affect the whole organism. This review outlines chemical compounds that are known inducers of RS and commonly used in laboratory research. These compounds act on replication by direct interaction with DNA causing DNA crosslinks and bulky lesions (cisplatin), chemical interference with the metabolism of deoxyribonucleotide triphosphates (hydroxyurea), direct inhibition of the activity of replicative DNA polymerases (aphidicolin) and interference with enzymes dealing with topological DNA stress (camptothecin, etoposide). As a variety of mechanisms can induce RS, the responses of mammalian cells also vary. Here, we review the activity and mechanism of action of these compounds based on recent knowledge, accompanied by examples of induced phenotypes, cellular readouts and commonly used doses.

show abstract

“…used for 5 days, capable of reversing infection in Swiss mice (Lozano et al ., 2016); and aphidicolin ( 28 ) derivatives obtained by semisynthesis exhibited high potency and selectivity against parasitic amastigote forms (Santos et al , 2016). Two of these derivatives gave IC 50 values of 0.6 μ M ( 28 A ) and 0.78 μ M ( 28 B ), with selectivity index > 100 for both (Figure 10) [68, 69].…”

Section: Introductionmentioning

confidence: 99%

Active Essential Oils and Their Components in Use against Neglected Diseases and Arboviruses

Luna

Scotti

et al. 2019

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

The termneglected diseasesrefers to a group of infections caused by various classes of pathogens, including protozoa, viruses, bacteria, and helminths, most often affecting impoverished populations without adequate sanitation living in close contact with infectious vectors and domestic animals. The fact that these diseases were historically not considered priorities for pharmaceutical companies made the available treatments options obsolete, precarious, outdated, and in some cases nonexistent. The use of plants for medicinal, religious, and cosmetic purposes has a history dating back to the emergence of humanity. One of the principal fractions of chemical substances found in plants are essential oils (EOs). EOs consist of a mixture of volatile and hydrophobic secondary metabolites with marked odors, composed primarily of terpenes and phenylpropanoids. They have great commercial value and were widely used in traditional medicine, by phytotherapy practitioners, and in public health services for the treatment of several conditions, including neglected diseases. In addition to the recognized cytoprotective and antioxidative activities of many of these compounds, larvicidal, insecticidal, and antiparasitic activities have been associated with the induction of oxidative stress in parasites, increasing levels of nitric oxide in the infected host, reducing parasite resistance to reactive oxygen species, and increasing lipid peroxidation, ultimately leading to serious damage to cell membranes. The hydrophobicity of these compounds also allows them to cross the membranes of parasites as well as the blood-brain barrier, collaborating in combat at the second stage of several of these infections. Based on these considerations, the aim of this review was to present an update of the potential of EOs, their fractions, and their chemical constituents, against some neglected diseases, including American and African trypanosomiasis, leishmaniasis, and arboviruses, specially dengue.

show abstract

Semisynthesis of new aphidicolin derivatives with high activity against Trypanosoma cruzi

Cited by 9 publications

References 19 publications

Diterpenes as lead molecules against neglected tropical diseases

Diterpenes as lead molecules against neglected tropical diseases

Common Chemical Inductors of Replication Stress: Focus on Cell‐Based Studies

Active Essential Oils and Their Components in Use against Neglected Diseases and Arboviruses

Contact Info

Product

Resources

About