ChemInform Abstract: Total Synthesis of the Isodon Diterpene Sculponeatin N.

Moritz, Benjamin J.; Mack, Daniel J.; Tong, Liuchuan; Thomson, Regan J.

doi:10.1002/chin.201434203

Cited by 1 publication

(1 citation statement)

References 21 publications

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“…Among these, enmein-type 6,7-seco-ent-kaurane diterpenoids have unique chemical skeletons and exhibit significant activities ( Figure 1) [3][4][5]. These natural enmein-type ent-kaurane diterpenoids with a lot of stereogenic centers and complex ring systems have attracted much attention [6][7][8][9][10][11][12][13][14][15]. Natural sources cannot afford large compound supply for structure modification.…”

Section: Introductionmentioning

confidence: 99%

NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

Han

et al. 2016

Molecules

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A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO) donor hybrids (10a-i) were designed and synthesized from commercially available oridonin (1). These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC 50 of 0.81 µM and could also release 33.7 µmol/L NO at the time point of 60 min. Compounds 10a-i also showed cytotoxic selectivity between tumor and normal liver cells with IC 50 ranging from 22.1 to 33.9 µM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations.

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