Antimalarial activity of a novel series of artemisinin-derived 1, 2, 3-triazole dimers
Journal Title: Asian Pacific Journal of Tropical Medicine - Year 2019, Vol 12, Issue 5
Abstract
Objective: To obtain suitable artimisinin-based drug candidates with high antimalarial activity. Methods: Three different reaction schemes were used to synthesize a total of 15 artemisininbased compounds. The first synthetic scheme involved the synthesis of diazido aliphatic and aromatic compounds from commercially available dihalides and azido derivatives of artemisinin. The second scheme consisted of the reaction of dibromoaliphatic compounds with sodium azide in dimethylformamide which yielded the desired compounds. Artemisinin-based compounds on treatment with sodium azide and bromotrimethylsilane in dichloromethane produced the most potent compound GB-2. Another potent compound GB-1 was synthesized from artemisinin by treatment with alcohols in the presence of Aberlyst-15 in anhydrous dichloromethane. The third scheme involved the Huisgen 1,3-dipolar cycloaddition between the synthesized aliphatic and aromatic diazides and two alkyne derivatives of artemisinin to obtain the desired artemisinin dimers with average yields. Results: The best in vitro antiplasmodial activity was shown by the compound GB-2 registering IC50 value 0.066 μg/mL against chloroquine-sensitive and 0.865 μg/mL against chloroquineresistant strains of Plasmodium falciparum. It suppressed 59.0% parasitaemia in vivo of rodent malaria parasite Plasmodium berghei in Swiss albino model at 50 μg/kg body weight dosage. Molecular docking interactions of Plasmodium falciparum ATP6 (PfATP6) protein revealed strong bonding of GB-2 with Thr255 residue which is likely to be the reason for excellent antimalarial activity of this compound. Conclusion: Two compounds GB-1 and GB-2 exhibited excellent in vitro antiplasmodial activity and fair in vivo antimalarial activity. Of the two, GB-2 showed better activity which could be attributed to its strong bonding interactions with Thr255 as evidenced from the molecular docking study. Study helped in identifying artemisinin analogues possessing good antimalarial properties and further research in structural alterations of the selected molecules should be carried out which may result in obtaining potent drug candidates against the malarial parasite.
Authors and Affiliations
Anil Prakash
Keywords
Related Articles
- EP ID EP573106
- DOI 10.4103/1995-7645.259240
- Views 57
- Downloads 0
Targeted inhibition of Notch1 gene enhances the killing effects of paclitaxel on triple negative breast cancer cells
Objective: To study the influence of targeted inhibition of Notch1 gene on the killing effects of paclitaxel on triple negative breast cancer cells. Methods: The triple negative [estrogen receptor (ER)/progesterone recep...
Morphometric discrimination between females of two isomorphic sand fly species, Phlebotomus caucasicus and Phlebotomus mongolensis (Diptera: Phlebotominae) in endemic and non-endemic foci of zoonotic cutaneous leishmaniasis in Iran
Objective: To delineate reliable morphological characteristics for identifying and separating female Phlebotomus caucasicus and Phlebotomus mongolensis which exist sympatrically in the main foci of zoonotic cutaneous l...
Community-acquired pneumonia with Acinetobacter radioresistens bacteremia in an immunocompetent host: A case report
Rationale: Acinetobacter radioresistens is a non-fermentative Gram-negative coccobacillus that is environmentally ubiquitous and is an uncommon cause of pneumonia in an immunocompetent patient with no known chronic medic...
Electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure
Objective: To investigate the electrophysiological changes of autonomic cells in left ventricular outflow tract in guinea pigs with iron deficiency anemia complicated with chronic heart failure. Methods: Guinea pigs mode...
Expression and mechanism of action of miR-196a in epithelial ovarian cancer
Objective: To explore the expression, biological function and possible mechanism of action of microRNA molecular-196a (miR-196a) in epithelial ovarian cancer. Methods: RT-PCR was used to detect the expression quantities...