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Oridonin, a Promising ent -Kaurane Diterpenoid Lead Compound

View Article: PubMed Central - PubMed

ABSTRACT

Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

No MeSH data available.


NO-releasing enmein-type 6,7-seco-kaurane diterpenoid derivatives 41 and 42.
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ijms-17-01395-f021: NO-releasing enmein-type 6,7-seco-kaurane diterpenoid derivatives 41 and 42.

Mentions: In this year, a series of NO-donating enmein-type diterpenoid derivatives (41) was designed and synthesized (Figure 21) [19]. The target derivatives showed potent antibacterial activity against Gram-positive bacteria S. aureus and B. subtilis with the most promising MICs of 4 and 2 μg/mL, respectively, while the MICs of oridonin were both 32 μg/mL. The antiproliferative activity against human tumor and human normal cells was also tested. Most of these NO-releasing molecules showed good cytotoxic selectivity and released high levels (above 20 μmol/L) of NO at the time point of 60 min. Compound 42 was the most promising one with IC50 values of 1.68, 1.11, 3.60 and 0.72 μM against K562, MGC-803, CaEs-17 and Bel-7402 cells and 18.80 μM against normal liver cell line L-02. The selectivity index (SI) of 42 between tumor and normal liver cells was about 26.1, while the SI of oridonin was only 2.4. Compound 42 also induced apoptosis by the mitochondria-related pathway and arrested Bel-7402 cell cycle at the S phase.


Oridonin, a Promising ent -Kaurane Diterpenoid Lead Compound
NO-releasing enmein-type 6,7-seco-kaurane diterpenoid derivatives 41 and 42.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037675&req=5

ijms-17-01395-f021: NO-releasing enmein-type 6,7-seco-kaurane diterpenoid derivatives 41 and 42.
Mentions: In this year, a series of NO-donating enmein-type diterpenoid derivatives (41) was designed and synthesized (Figure 21) [19]. The target derivatives showed potent antibacterial activity against Gram-positive bacteria S. aureus and B. subtilis with the most promising MICs of 4 and 2 μg/mL, respectively, while the MICs of oridonin were both 32 μg/mL. The antiproliferative activity against human tumor and human normal cells was also tested. Most of these NO-releasing molecules showed good cytotoxic selectivity and released high levels (above 20 μmol/L) of NO at the time point of 60 min. Compound 42 was the most promising one with IC50 values of 1.68, 1.11, 3.60 and 0.72 μM against K562, MGC-803, CaEs-17 and Bel-7402 cells and 18.80 μM against normal liver cell line L-02. The selectivity index (SI) of 42 between tumor and normal liver cells was about 26.1, while the SI of oridonin was only 2.4. Compound 42 also induced apoptosis by the mitochondria-related pathway and arrested Bel-7402 cell cycle at the S phase.

View Article: PubMed Central - PubMed

ABSTRACT

Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

No MeSH data available.