Arteether (6) has been prepared from dihydroquinghaosu (3) by etherification with ethanol in the presence of Lewis acid and separated from its chromatographically slower moving alpha-dihydroqinghaosu ethyl ether (7). The absolute stereochemistry at C-12 has been determined by 1H NMR data (J11,12, NOESY). Ethyl ethers 6 and 7 showed potent in vitro inhibition of Plasmodium falciparum, and both compounds were highly potent antimalarials in mice infected with a drug-sensitive strain of Plasmodium berghei. Crystalline arteether (6) and its oily epimer 7 were 2-3 times more potent schizontocides than quinghaosu (1), but deoxy compounds 8, 9, and 11 were 100-300 times less potent in vitro than their corresponding peroxy precursors. Pharmacological studies have shown arteether(6) to have antimalarial activity in animals comparable to artesunate (2) and artemether (4), both of which are fast-acting blood schizontocides in humans. Arteether (6) has now been chosen for a clinical evaluation in high-risk malaria patients.

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Cirsium japonicum DC, a traditional Chinese medicine, has been widely used as an antihemorrhagic and diuretic agent. The objective of this study was to perform quantitative analysis of flavone by reversed-phase HPLC and examine the anticancer activity of C. japonicum DC in the S180 and H22 mice. Cirsium japonicum DC was separated and purified with several chromatography techniques and two flavone compounds, pectolinarin and 5,7-dihydroxy-6,4'-dimethoxyflavone, were isolated. The content of these two compounds in the methanol, ethanol, and aqueous extractions respectively was determined by HPLC as follows: pectolinarin 1.87%, 1.65%, 1.27%; 5,7-dihydroxy-6,4'-dimethoxyflavone: 0.515%, 0.42%, 0.221%. Furthermore, the effect of the two flavones on the anticancer activity in S180 and H22 mice was studied. Our research shows that these two flavones greatly inhibit cancer cell growth. The rate of inhibiting S180 mice was 55.77% at 50 mg kg( - 1), and the rate of life lengthening was 99.13% at 50 mg kg( - 1) in H22 mice.

Abstract. The aim of the study was to investigate the potential of nanosuspension to enhance the bioavailability of SKLB610 (Biopharmaceutical Classification System class II drug), a bioactive anticancer compound synthesized in our labs. SKLB610 nanosuspensions were prepared using wet media milling. Physicochemical characteristics of the nanosuspensions were evaluated, including particle size and distribution, dissolution, transmission electron microscopy, atomic force microscopy, thermogravimetric analysis, and X-ray powder diffractometry. The dissolution rate of SKLB610 was greatly improved in nanosuspensions, compared to crude SKLB610. Pharmacokinetic studies in rats demonstrated that the oral bioavailability of SKLB610 in nanosuspension (89.4%) was 2.6-fold higher than in coarse suspension (34.1%). Stabilizer type, milling time, and milling speed had a significant effect on particle size of the SKLB610 nanosuspensions. Nanosuspensions effectively improved the dissolution rate and bioavailability of the water-insoluble drug SKLB610 by reducing the compound particle size to the nanoscale and employing a proper formulation.