Englerin A, a Selective Inhibitor of Renal Cancer Cell Growth, from Phyllanthus engleri

Abstract

An extract from Phyllanthus engleri was identified in a bioinformatic analysis of NCI 60-cell natural product extract screening data, that selectively inhibited the growth of renal cancer cell lines. Bioassay guided fractionation yielded two new guaiane sesquiterpenes, englerins A (1) and B (2). Englerin A showed 1000-fold selectivity against 6 of 8 renal cancer cell lines with GI50 values ranging from 1-87 nM. The structures of 1 and 2 and their relative stereochemistry were established by spectroscopic methods.

Asymmetric, Protecting‐Group‐Free Total Synthesis of (−)‐Englerin A

“…The spectroscopic data of our synthetic 1 are in agreement with those reported for natural englerin A. [1,19] In conclusion, an asymmetric total synthesis of (À)-englerin A has been achieved in 15 steps with 8.1 % overall yield by starting from (R)-citronellal. The synthesis is concise and features several key transformations, namely, a goldcatalyzed cyclization of an enyne and a hydroxy-directed hydrogenation of an olefin.…”

“…[1] This species was collected from a plant growing in East Africa. Biological evaluation revealed that englerin A has potent ability to inhibit renal cancer cell growth with GI 50 values (growth inhibition of 50%) ranging from 1-87 nm.…”

“…Structure-activity relationship investigations of englerin A would be helpful for explaining this difference, and then also helpful in identifying analogues for further development as drug targets. These studies are of vital importance because kidney cancer is a major cause of morbidity and mortality in adults, [1] and until now no satisfactory drugs are available for its treatment. Given this background, it is not surprising that synthetic interest in this target has been considerable.…”

Five new sucrose esters from the whole plants of Phyllanthus cochinchinensis

“…Further column chromatography (CC) over Diaion HP20SS, Sephadex LH-20 and silica gel, followed with semipreparative HPLC purification of the MeOH extract yielded five new compounds (1)(2)(3)(4)(5), together with two known ones. The known compounds were elucidated as jasminoside (6) 6 and jaslanceoside B (7) 7 by comparison of their spectroscopic data with reported literature values.…”

“…Previous chemical studies on this genus have revealed the occurrence of flavonoids, alkaloids, sesquiterpenoids, triterpenoids, lignans, and tannins. [1][2][3][4][5] Among them, some sesquiterpenoids exhibited potent antiviral activity against coxsackie virus B3 (CVB3), 4 and inhibition of the growth of murine P-388 lymphocytic leukemia cell line. 5 P. cochinchinensis, a shrub up to 3 m height, is mainly growing in the montane sparse forests, forest margins, scrub on slopes, and wastelands of the southern part of China.…”