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Ten alkaloids ( 1 – 10 ), with sophoridine ( 1 ) as the most abundant component, were obtained from the whole plants of Oxytropis ochrocephala Bunge. Furthermore, eight new sophoridine derivatives ( 11 – 16 , 20 , 21 ), with modification on the C-14 position of 1 were synthesized. All compounds ( 1 – 16 , 20 , 21 ) were evaluated for antiproliferative activity against five human tumor cell lines. Among them, the newly synthesized derivative 20 exhibited the best inhibitory activity against the tested cell lines. Its activity was increased by more than fourfold as compared with parent compound 1 . [ABSTRACT FROM AUTHOR]

Betulinic acid (BA), a pentacyclic triterpenoid, exhibits broad spectrum antiproliferative activity, but generally with only modest potency. To improve BA's pharmacological properties, fluorine was introduced as a single atom at C-2, creating two diastereomers, or in a trifluoromethyl group at C-3. We evaluated the impact of these groups on antiproliferative activity against five human tumor cell lines. A racemic 2-F-BA (compound 6) showed significantly improved antiproliferative activity, while each diastereomer exhibited similar effects. We also demonstrated that 2-F-BA is a topoisomerase (Topo) I and IIα dual inhibitor in cell-based and cell-free assays. A hypothetical mode of binding to the Topo I-DNA suggested a difference between the hydrogen bonding of BA and 2-F-BA to DNA, which may account for the difference in bioactivity against Topo I. [ABSTRACT FROM AUTHOR]

Abstract: In our ongoing study of the desmosdumotin C (1) series, twelve new analogues, 21–32, mainly with structural modifications in ring-A, were prepared and evaluated for in vitro antiproliferative activity against several human tumor cell lines. Among them, the 4′-iodo-3,3,5-tripropyl-4-methoxy analogue (31) showed significant antiproliferative activity against multiple human tumor cell lines with ED50 values of 1.1–2.8μM. Elongation of the C-3 and C-5 carbon chains reduced activity relative to propyl substituted analogues; however, activity was still better than that of natural compound 1. Among analogues with various ether groups on C-4, compounds with methyl (2) and propyl (26) ethers inhibited cell growth of multiple tumor cells lines, while 28 with an isobutyl ether showed selective antiproliferative activity against lung cancer A549 cells (ED50 1.7μM). The gene expression profiles showed that 3 may modulate the spindle assembly checkpoint (SAC) and chromosome separation, and thus, arrest cells at the G2/M-phase. [Copyright &y& Elsevier]

• Two new furanoquinolones, racemic 3-oxolunacrine (1) and 2,3-dehydrolunacrine (2), were isolated from Lunasia amara. • Pure (S)- and (R)-isomers of 1 were separated by chiral column chromatography. • The possibility that racemic 1 occurs naturally was discussed based on a proposed biosynthetic pathway. Two new furanoquinolones, 3-oxolunacrine (1) and 2,3-dehydrolunacrine (2), and 22 known quinolones (3–24) were isolated from the methanol extract of the bark of Lunasia amara. The chemical structures of the newly isolated compounds were elucidated from HRMS and various NMR spectroscopic data. Pure (S)- and (R)-isomers of 1 , which was obtained as a racemate, were separated by chiral column chromatography. The possibility that racemic 1 occurs naturally was discussed based on a proposed biosynthetic pathway. Selected isolated quinoline alkaloids were evaluated for antiproliferative activities against five human tumor cell lines, including a multidrug-resistant cell line overexpressing p-glycoprotein. [ABSTRACT FROM AUTHOR]