| Autor: |
Liliane Abodo Onambele, Herbert Riepl, Rainer Fischer, Gabriele Pradel, Aram Prokop, Makoah Nigel Aminake |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
International Journal for Parasitology: Drugs and Drug Resistance, Vol 5, Iss 2, Pp 48-57 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2211-3207 |
| DOI: |
10.1016/j.ijpddr.2015.03.002 |
| Popis: |
Malaria remains one of the most deadly diseases threatening humankind and is still affecting a significant proportion of the world population, especially in Africa. Chemotherapy is a vital component of the fight against the disease and new antimalarial agents are urgently needed to curb the spread of malaria parasites that are resistant to existing drugs. The natural product tryptanthrin is known for its wide range of activities, including antiplasmodial activity, but its poor solubility has undermined its development as potent antimicrobial and antiprotozoan agent. The aim of this work was to synthesize analogues of tryptanthrin and to evaluate their antiplasmodial activity against the asexual and sexual blood stages of Plasmodium falciparum. Our results suggest that most tryptanthrin analogues retained their antiplasmodial activity against chloroquine-sensitive and chloroquine-resistant malaria parasites in the nanomolar range (30–100 nM). The antiplasmodial activity of the most active compound NT1 (IC50: 30 nM; SI: 155.9) was similar in both strains and close to that of chloroquine (IC50: 20 nM) on the sensitive strain. The antiplasmodial activity was improved with derivatization, thus pointing out the necessity to explore tryptanthrin using medicinal chemistry approaches. Ten (10) of the tested derivatives met the criteria, allowing for advancement to animal testing, i.e., SI > 100 and IC50 |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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