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
Citations
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Advances in quantitative structure–activity relationship models of antimalarials
Kunal Roy,Probir Kumar Ojha +1 more
TL;DR: In this paper, the authors focus on the current knowledge of quantitative structure-activity relationship (QSAR) and pharmacophore models of different classes of antimalarial drugs.
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Structural optimization and biological evaluation for novel artemisinin derivatives against liver and ovarian cancers.
Yu Zhou,Xiaoguang Li,Kerong Chen,Qian Ba,Xu Zhang,Jingquan Li,Jinfang Wang,Hui Wang,Hong Liu +8 more
TL;DR: Four compounds were selected to further evaluate their antitumor activities in in-vitro and in vivo ovarian and liver cancer models, and the results indicated that compound 18 exhibited the best therapeutic effect, not only effectively inhibited the growth of 7404 xenograft and Huh7 Xenograft, but also presented a good dose-dependent inhibition toward thegrowth of A2780 xenografted.
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Artesunate plus sulfamethoxypyrazine/pyrimethamine for the treatment of cutaneous leishmaniasis: a double-blind, placebo-controlled clinical trial.
Ishag Adam,Amel A. Hagelnur +1 more
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De novo identification and stability of the artemisinin pharmacophore: Studies of the reductive decomposition of deoxyartemisinins and deoxyarteethers and the implications for the mode of antimalarial action
TL;DR: In this article, the authors investigated the reaction of Seco and carba analogues of artemisinin 1 and arteether 16 using DFT (B3LYP/6-31+G * level).
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Antimalarial compound identification and design: advances in the patent literature, 2000 – 2003
TL;DR: Patents disclosing novel classes of antimalarial drugs were scarce, which may mean that the target-directed screening effort in malaria has not yet come to fruition, has not been commercially exploited in an appropriate manner, or that next generation compounds in known drug classes are more viable commercial entities.
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.
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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.