Biotechnological Approaches for Production of Artemisinin,an Anti-Malarial Drug from Artemisia annua L.

Artemisinin is an anti-malarial sesquiterpene lactone derived from Artemisia annua L. (Asteraceae family). One of the most widely used modes of treatment for malaria is an artemisinin-based combination therapy. Artemisinin and its associated compounds have a variety of pharmacological qualities that have helped achieve economic prominence in recent years. So far, research on the biosynthesis of this bioactive metabolite has revealed that it is produced in glandular trichomes and that the genes responsible for its production must be overexpressed in order to meet demand. Using biotechnological applications such as tissue culture, genetic engineering, and bioreactor-based approaches would aid in the upregulation of artemisinin yield, which is needed for the future. The current review focuses on the tissue culture aspects of propagation of A. annua and production of artemisinin from A. annua L. cell and organ cultures. The review also focuses on elicitation strategies in cell and organ cultures, as well as artemisinin biosynthesis and metabolic engineering of biosynthetic genes in Artemisia and plant model systems.     

A new route to novel 10-deoxoartemisinins

A series of novel 10-deoxoartemisinin derivatives was synthesized with high regioselectivity and yields using Heck reactions from 10β-allyldeoxoartemisinin. The configuration of the double bond of the product was determined from ¹H NMR coupling constants (J_2′-3′).     

青蒿截疟组合物与牛血清白蛋白的相互作用

利用荧光光谱法研究青蒿截疟组合物(青蒿素、青蒿乙素、青蒿酸与东莨菪内酯质量比为1∶1∶1∶1的混合体系,AAAS)与牛血清白蛋白(BSA)的相互作用.结果表明,与青蒿素单独作用相比,AAAS对BSA的荧光猝灭作用增强,并以静态猝灭为主;计算了298,303和310 K下的结合常数、结合位点数和热力学参数,表明AAAS与BSA之间具有较强的静电引力,相互作用过程是一个熵增加的自发分子间作用过程.AAAS对BSA的猝灭常数和结合常数均增大.结果表明,AAAS显著增加了青蒿素与血清白蛋白的结合作用,此过程可能是AAAS增加青蒿素抗疟疗效的重要体内环节.     

High performance liquid chromatographic evaluation of artemisinin,raw material in the synthesis of artesunate and artemether

A barrier to the development of artemisinin derivative based combination treatment of malaria is the lack of defined specifications and purity test methods for the raw material artemisinin. An HPLC method previously published in the International Pharmacopoeia to evaluate purity of artemisinin as an active pharmaceutical ingredient is adapted for use. Excellent method precision and linearity are demonstrated along with observations of robustness. In support of the development of specifications major impurities are identified using high resolution HPLC–MS, isolation via preparative HPLC followed by NMR. The identified impurities differ from those previously claimed.     

Measurement and correlation of solubility of artemisinin in supercritical carbon dioxide

Artemisinin is an effective antimalarial drug isolated from the herbal medicine Artemisia annua L. Supercritical fluid extraction is an environment-friendly method for the extraction of artemisinin. In this work, the solubility of artemisinin in supercritical carbon dioxide was determined by static method at three temperatures of 313 K, 323 K, 333 K and pressures from 11 to 31 MPa. The range of experimental solubility data was from 0.498 × 10⁻³ to 2.915 × 10⁻³ mol/mol under the above-mentioned conditions. Two density-based models (Chrastil and Mendez–Santiago–Teja models) were selected to correlate the experimental data of this work, and the average absolute relative deviation (AARD) was 8.32% and 8.33%, respectively. The correlation results showed good agreement with the experimental data.     

Recent Advances in Malaria Chemotherapy

A short review of the currently used antimalarial drugs is reported. The molecular aspects of the different possible mechanisms of action of artemisinin is documented, including recent data on heme alkylation. The preparation and the in vitro antimalarial activity of new modular molecules named “trioxaquines” is also presented.     

Determination of artemisinin and artemisinic acid by capillary and packed supercritical fluid chromatography

Artemisinin (an antimalarial compound) and its bioprecursor artemisinic acid, present in the plant Atemisia annua L., were analyzed by supercritical fluid chromatography (SFS) using capillary and packed columns, coupled respectively with a flame ionization detector (FID) and an evaporative light scattering detector (ELSD). Both methods were optimized and validated with columns of different polarity in order to separate artemisinin and artemisinic acid. Analytical results were comparable, but the paced SFC-ELSD method was faster. Indeed, artemisinin and artemisinic acid were separated with an aminopropyl silica column in less than 8 minutes instead of about 25 minutes by capillary SFS. Contrary to conventional gas and liquid chromatography coupled to an UV-visible detector, SFS methods determined both compounds directly, without degradation and/or derivatization in the concentration range expected in the plant material. Results obtained on plant extracts by capillary SFS-FID and packed SFS-ELSD were confirmed by GC-MS.