In vitro antitrypanosomal activity of African plants used in traditional medicine in Uganda to treat sleeping sickness

: 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.

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Zingiber zerumbet(L.) Smith: A Review of Its Ethnomedicinal, Chemical, and Pharmacological Uses

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2011/543216 ◽

2011 ◽

Vol 2011 ◽

pp. 1-12 ◽

Cited By ~ 80

Author(s):

N. J. Yob ◽

S. Mohd. Jofrry ◽

M. M. R. Meor. Mohd. Affandi ◽

L. K. Teh ◽

M. Z. Salleh ◽

...

Keyword(s):

Medicinal Plant ◽

Traditional Medicine ◽

Biological Evaluation ◽

Perennial Herb ◽

Zingiber Zerumbet ◽

Tropical Countries ◽

Traditional Uses ◽

Worm Infestation

Zingiber zerumbetSm., locally known to the Malay as “Lempoyang,” is a perennial herb found in many tropical countries, including Malaysia. The rhizomes ofZ. zerumbet, particularly, have been regularly used as food flavouring and appetizer in various Malays' cuisines while the rhizomes extracts have been used in Malay traditional medicine to treat various types of ailments (e.g., inflammatory- and pain-mediated diseases, worm infestation and diarrhea). Research carried out using differentin vitroandin vivoassays of biological evaluation support most of these claims. The active pharmacological component ofZ. zerumbetrhizomes most widely studied is zerumbone. This paper presents the botany, traditional uses, chemistry, and pharmacology of this medicinal plant.

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Ethnomedicinal survey and in vitro confirmation of anti-inflammatory and antispasmodic properties of the termite strain Macrotermes bellicosus used in traditional medicine in the Republic of Benin.

Journal of Ethnopharmacology ◽

10.1016/j.jep.2020.112705 ◽

2020 ◽

Vol 254 ◽

pp. 112705 ◽

Cited By ~ 1

Author(s):

Dima Hammoud Mahdi ◽

Dirk K. Wissenbach ◽

Martin von Bergen ◽

Zacharie Vissiennon ◽

Daniel Chougourou ◽

...

Keyword(s):

Traditional Medicine ◽

Macrotermes Bellicosus ◽

Anti Inflammatory ◽

Republic Of Benin ◽

The Republic

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Antitrypanosomal activity of purine nucleosides can be enhanced by their conversion to O-acetylated derivatives.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.11.2567 ◽

1996 ◽

Vol 40 (11) ◽

pp. 2567-2572 ◽

Cited By ~ 11

Author(s):

J R Sufrin ◽

D Rattendi ◽

A J Spiess ◽

S Lane ◽

C J Marasco ◽

...

Keyword(s):

Trypanosoma Brucei ◽

Parent Compound ◽

Nucleoside Analogs ◽

Significant Activity ◽

Structural Class ◽

Antitrypanosomal Activity ◽

Salvage Pathways ◽

Purine Salvage Pathways

Fifteen purine nucleosides and their O-acetylated ester derivatives were examined for in vitro antitrypanosomal activity against the LAB 110 EATRO isolate of Trypanosoma brucei brucei and two clinical isolates of Trypanosoma brucei rhodesiense. Initial comparisons of activity were made for the LAB 110 EATRO isolate. Three nucleoside analogs exhibited no significant activity (50% inhibitory concentrations [IC50s] of > 100 microM), whether they were O acetylated or unacetylated; three nucleosides showed almost equal activity (IC50s of < 5 microM) for the parent compound and the O-acetylated derivative; nine nucleosides showed significantly improved activity (> or = 3-fold) upon O acetylation; of these nine analogs, six displayed activity at least 10-fold greater than that of their parent nucleosides. The most significant results were those for four apparently inactive compounds which, upon O acetylation, displayed IC50s of < or = 25 microM. When the series of compounds was tested against T. brucei rhodesiense isolates (KETRI 243 and KETRI 269), their antitrypanosomal effects were comparable to those observed for the EATRO 110 strain. Thus, our studies of purine nucleosides have determined that O acetylation consistently improved their in vitro antitrypanosomal activity. This observed phenomenon was independent of their cellular enzyme targets (i.e., S-adenosylmethionine, polyamine, or purine salvage pathways). On the basis of our results, the routine preparation of O-acetylated purine nucleosides for in vitro screening of antitrypanosomal activity is recommended, since O acetylation transformed several inactive nucleosides into compounds with significant activity, presumably by improving uptake characteristics. O-acetylated purine nucleosides may offer in vivo therapeutic advantages compared with their parent nucleosides, and this possibility should be considered in future evaluations of this structural class of trypanocides.

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Targeting the Variable Surface of African Trypanosomes with Variant Surface Glycoprotein-Specific, Serum-Stable RNA Aptamers

Eukaryotic Cell ◽

10.1128/ec.2.1.84-94.2003 ◽

2003 ◽

Vol 2 (1) ◽

pp. 84-94 ◽

Cited By ~ 55

Author(s):

Mihaela Lorger ◽

Markus Engstler ◽

Matthias Homann ◽

H. Ulrich Göringer

Keyword(s):

Antigenic Variation ◽

Sleeping Sickness ◽

Rna Aptamers ◽

Surface Glycoprotein ◽

Variant Surface Glycoprotein ◽

Parasite Protein ◽

African Trypanosomes ◽

Variable Surface ◽

New Strategy

ABSTRACT African trypanosomes cause sleeping sickness in humans and Nagana in cattle. The parasites multiply in the blood and escape the immune response of the infected host by antigenic variation. Antigenic variation is characterized by a periodic change of the parasite protein surface, which consists of a variant glycoprotein known as variant surface glycoprotein (VSG). Using a SELEX (systematic evolution of ligands by exponential enrichment) approach, we report the selection of small, serum-stable RNAs, so-called aptamers, that bind to VSGs with subnanomolar affinity. The RNAs are able to recognize different VSG variants and bind to the surface of live trypanosomes. Aptamers tethered to an antigenic side group are capable of directing antibodies to the surface of the parasite in vitro. In this manner, the RNAs might provide a new strategy for a therapeutic intervention to fight sleeping sickness.

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Activity of Indenoisoquinolines against African Trypanosomes

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00650-07 ◽

2008 ◽

Vol 53 (1) ◽

pp. 123-128 ◽

Cited By ~ 11

Author(s):

Rahul P. Bakshi ◽

Dongpei Sang ◽

Andrew Morrell ◽

Mark Cushman ◽

Theresa A. Shapiro

Keyword(s):

Anticancer Agents ◽

Mammalian Cells ◽

Sleeping Sickness ◽

Water Soluble ◽

African Trypanosomes ◽

In Vivo Experiments ◽

Topoisomerase Ib ◽

Topoisomerase Poisons

ABSTRACT African trypanosomiasis (sleeping sickness), caused by protozoan Trypanosoma brucei species, is a debilitating disease that is lethal if untreated. Available drugs are antiquated, toxic, and compromised by emerging resistance. The indenoisoquinolines are a class of noncamptothecin topoisomerase IB poisons that are under development as anticancer agents. We tested a variety of indenoisoquinolines for their ability to kill T. brucei. Indenoisoquinolines proved trypanocidal at submicromolar concentrations in vitro. Structure-activity analysis yielded motifs that enhanced potency, including alkylamino substitutions on N-6, methoxy groups on C-2 and C-3, and a methylenedioxy bridge between C-8 and C-9. Detailed analysis of eight water-soluble indenoisoquinolines demonstrated that in trypanosomes the compounds inhibited DNA synthesis and acted as topoisomerase poisons. Testing these compounds on L1210 mouse leukemia cells revealed that all eight were more effective against trypanosomes than against mammalian cells. In preliminary in vivo experiments one compound delayed parasitemia and extended survival in mice subjected to a lethal trypanosome challenge. The indenoisoquinolines provide a promising lead for the development of drugs against sleeping sickness.

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Foeniculum vulgareMill: A Review of Its Botany, Phytochemistry, Pharmacology, Contemporary Application, and Toxicology

BioMed Research International ◽

10.1155/2014/842674 ◽

2014 ◽

Vol 2014 ◽

pp. 1-32 ◽

Cited By ~ 90

Author(s):

Shamkant B. Badgujar ◽

Vainav V. Patel ◽

Atmaram H. Bandivdekar

Keyword(s):

Traditional Medicine ◽

Scientific Evidence ◽

New Drugs ◽

Future Research ◽

Foeniculum Vulgare ◽

Wide Range ◽

Research Findings ◽

Valuable Compounds

Foeniculum vulgareMill commonly called fennel has been used in traditional medicine for a wide range of ailments related to digestive, endocrine, reproductive, and respiratory systems. Additionally, it is also used as a galactagogue agent for lactating mothers. The review aims to gather the fragmented information available in the literature regarding morphology, ethnomedicinal applications, phytochemistry, pharmacology, and toxicology ofFoeniculum vulgare. It also compiles available scientific evidence for the ethnobotanical claims and to identify gaps required to be filled by future research. Findings based on their traditional uses and scientific evaluation indicates thatFoeniculum vulgareremains to be the most widely used herbal plant. It has been used for more than forty types of disorders. Phytochemical studies have shown the presence of numerous valuable compounds, such as volatile compounds, flavonoids, phenolic compounds, fatty acids, and amino acids. Compiled data indicate their efficacy in severalin vitroandin vivopharmacological properties such as antimicrobial, antiviral, anti-inflammatory, antimutagenic, antinociceptive, antipyretic, antispasmodic, antithrombotic, apoptotic, cardiovascular, chemomodulatory, antitumor, hepatoprotective, hypoglycemic, hypolipidemic, and memory enhancing property.Foeniculum vulgarehas emerged as a good source of traditional medicine and it provides a noteworthy basis in pharmaceutical biology for the development/formulation of new drugs and future clinical uses.

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