Journal ArticleDOI
Structure-activity relationships of the antimalarial agent artemisinin. 8. design, synthesis, and CoMFA studies toward the development of artemisinin-based drugs against leishmaniasis and malaria.
Mitchell A. Avery,K. M. Muraleedharan,Prashant V. Desai,Achintya K Bandyopadhyaya,Marise M Furtado,Babu L. Tekwani +5 more
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TLDR
The study suggests the possibility of developing artemisinin analogues as potential drug candidates against both malaria and leishmaniasis.Abstract:
Artemisinin (1) and its analogues have been well studied for their antimalarial activity. Here we present the antimalarial activity of some novel C-9-modified artemisinin analogues synthesized using artemisitene as the key intermediate. Further, antileishmanial activity of more than 70 artemisinin derivatives against Leishmania donovani promastigotes is described for the first time. A comprehensive structure-activity relationship study using CoMFA is discussed. These analogues exhibited leishmanicidal activity in micromolar concentrations, and the overall activity profile appears to be similar to that against malaria. Substitution at the C-9beta position was shown to improve the activity in both cases. The 10-deoxo derivatives showed better activity compared to the corresponding lactones. In general, compounds with C-9alpha substitution exhibited lower antimalarial as well as antileishmanial activities compared to the corresponding C-9beta analogues. The importance of the peroxide group for the observed activity of these analogues against leishmania was evident from the fact that 1-deoxyartemisinin analogues did not exhibit antileishmanial activity. The study suggests the possibility of developing artemisinin analogues as potential drug candidates against both malaria and leishmaniasis.read more
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A new approach for the delivery of artemisinin: Formulation, characterization, and ex-vivo antileishmanial studies
Muzamil Y Want,Mohammad Islamuddin,Garima Chouhan,Anjan Kumar Dasgupta,Asoke P. Chattopadhyay,Farhat Afrin +5 more
TL;DR: Treatment with art Artemisinin-loaded nanoparticles significantly reduced the number of amastigotes per macrophage and percent infected macrophages ex vivo compared to free artemisinin, and these nanoparticles were also non-toxic to Macrophages compared to artemis inin alone.
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Reactions of artemisinin and arteether with acid: Implications for stability and mode of antimalarial action
TL;DR: The currently accepted mechanism of trioxane antimalarial action involves generation of free radicals within or near susceptible sites probably arising from the production of distonic radical anions and this investigation has established the preferred Lewis acid protonation sites.
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Electrospun Nanofibers of Polycaprolactone/Collagen as a Sustained-Release Drug Delivery System for Artemisinin.
TL;DR: In this paper, the performance of ART-loaded polycaprolactone (PCL)/collagen (Col) nanofibers with different proportions of polymers were characterized and further ART anti-crystallization and release behaviors were studied.
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QSAR modeling, docking and ADMET studies for exploration of potential anti-malarial compounds against Plasmodium falciparum.
TL;DR: 2D-QSAR model and molecular docking were used to evaluate the Artemisinin compounds and to reveal their binding modes and structural basis of inhibitory activity, and four chemical descriptors have been found to be well correlated with anti-malarial activities.
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Antipromastigote activity of an ethanolic extract of leaves of Artemisia indica
TL;DR: The antileishmanial efficacy of an ethanolic extract of an indigenous medicinal plant Artemisia indica is reported, which has been used for general malaise and fevers of unknown origin, whereas artemisinins, the sesquiterpine lactones isolated from A. annua have been used to treat multidrug-resistant malaria.
References
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Journal ArticleDOI
Iterative partial equalization of orbital electronegativity – a rapid access to atomic charges
Johann Gasteiger,Mario Marsili +1 more
TL;DR: In this article, a method for the rapid calculation of atomic charges in σ-bonded and nonconjugated π-systems is presented, where only the connectivities of the atoms are considered.
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Qinghaosu (artemisinin): an antimalarial drug from China
TL;DR: Derivatives of QHS, such as dihydroqinghaosu, artemether, and the water-soluble sodium artesunate, appear to be more potent than QHS itself, and offer promise as a totally new class of antimalarials.
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Crossvalidation, Bootstrapping, and Partial Least Squares Compared with Multiple Regression in Conventional QSAR Studies
TL;DR: To better evaluate, in the context of QSAR studies, new validation techniques such as bootstrapping and crossvalidation and the new analytic technique of partial least squares, seventeenQSAR results taken from nine recent publications were reexamined using these techniques.
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Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells
Narendra P. Singh,Henry Lai +1 more
TL;DR: It is reported here that after incubation with holotransferrin, which increases the concentration of ferrous iron in cancer cells, dihydroartemisinin, an analog of artemis inin, effectively killed a type of radiation-resistant human breast cancer cell in vitro.
Journal ArticleDOI
Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu).
Steven R. Meshnick,Ying-Zi Yang,V. Lima,F. Kuypers,Sumalee Kamchonwongpaisan,Yongyuth Yuthavong +5 more
TL;DR: Iron probably catalyzes the generation of free radicals from artemisinin since alpha-tocopherol antagonizes the thiol-oxidizing activity of art Artemisinin and since a spin-trapped free radical signal can be seen by electron paramagnetic resonance only when artemis inin is incubated in the presence of iron.