1301159-83-0Relevant academic research and scientific papers
A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones
Elbel, Kristyna M.,Guizzunti, Gianni,Theodoraki, Maria A.,Xu, Jing,Batova, Ayse,Dakanali, Marianna,Theodorakis, Emmanuel A.
, p. 3341 - 3348 (2013)
Natural products of the caged Garcinia xanthones (CGX) family are characterized by a unique chemical structure, potent bioactivities and promising pharmacological profiles. We have developed a Claisen/Diels-Alder reaction cascade that, in combination with a Pd(0)-catalyzed reverse prenylation, provides rapid and efficient access to the CGX pharmacophore, represented by the structure of cluvenone. To further explore this pharmacophore, we have synthesized various A-ring oxygenated analogues of cluvenone and have evaluated their bioactivities in terms of growth inhibition, mitochondrial fragmentation, induction of mitochondrial-dependent cell death and Hsp90 client inhibition. We found that installation of an oxygen functionality at various positions of the A-ring influences significantly both the site-selectivity of the Claisen/Diels-Alder reaction and the bioactivity of these compounds, due to remote electronic effects.
Studies on chemical modification and biology of a natural product, gambogic acid (III): Determination of the essential pharmacophore for biological activity
Wang, Xiaojian,Lu, Na,Yang, Qian,Gong, Dandan,Lin, Changjun,Zhang, Shenglie,Xi, Meiyang,Gao, Yuan,Wei, Libing,Guo, Qinglong,You, Qidong
, p. 1280 - 1290 (2011/04/22)
Caged 4-oxa-tricyclo[4.3.1.03,7]dec-2-one structural motifs are found in Garcinia natural products that demonstrate anti-tumor activity. Gambogic acid (GA, 1), the most abundant caged Garcinia xanthones, has been reported to be a promising anti-cancer agent. To identify the essential pharmacophore for its anti-tumor activity, a series of GA analogues that address potential key structural features for biological activity were synthesized, among which compound 11a displayed comparable in vitro anti-tumor activity as GA. Mechanistic studies on 11a determined that the compound induces apoptosis as well as arrests the G2/M phase of the cell cycle in HepG2 cells. The determination of the essential part of the scaffold found in GA to maintain anti-tumor effects, and the SAR based on the caged pharmacophore are reported and will provide key information for future anti-cancer drug development studies.
