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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.


Synthesis of 1-O and 14-O-derivatives (14–17) of oridonin.
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ijms-17-01395-f008: Synthesis of 1-O and 14-O-derivatives (14–17) of oridonin.

Mentions: In the year 2008, our research group published our first work in the field of the structural modification of oridonin [41]. Some 1-O and 14-O-derivatives of oridonin were synthesized (Figure 8) and biologically evaluated against six cancer cell lines (SW-480, BGC-7901, HL-60, A549, Bel-7402 and B16). All of the derivatives exhibited stronger cytotoxicity than oridonin in vitro, and three of them were further evaluated in vivo. Derivatives 16 and 17 showed the most potent antiproliferative activity against HL-60 and Bel-7402 cell lines with the IC50 values of 0.84 and 1.00 μM, respectively. The preliminary SAR suggested that the introduction of both terminal carboxylic acid and the ester side chain of the lipophilicity moiety to the 14-O position of oridonin appeared to increase the antiproliferative activity. The cytotoxicity of the derivatives with the substituent of acetyl at the 1-O position was better than those with the propylsulfonyl group and the 1-hydroxyl oxidated derivatives. Compounds 16 and 17 also had stronger anti-tumor activity in mice bearing H22 liver tumor than oridonin (45.9%) with the inhibition ratios of 69.9% and 61.2%, correspondingly.


Oridonin, a Promising ent -Kaurane Diterpenoid Lead Compound
Synthesis of 1-O and 14-O-derivatives (14–17) of oridonin.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-17-01395-f008: Synthesis of 1-O and 14-O-derivatives (14–17) of oridonin.
Mentions: In the year 2008, our research group published our first work in the field of the structural modification of oridonin [41]. Some 1-O and 14-O-derivatives of oridonin were synthesized (Figure 8) and biologically evaluated against six cancer cell lines (SW-480, BGC-7901, HL-60, A549, Bel-7402 and B16). All of the derivatives exhibited stronger cytotoxicity than oridonin in vitro, and three of them were further evaluated in vivo. Derivatives 16 and 17 showed the most potent antiproliferative activity against HL-60 and Bel-7402 cell lines with the IC50 values of 0.84 and 1.00 μM, respectively. The preliminary SAR suggested that the introduction of both terminal carboxylic acid and the ester side chain of the lipophilicity moiety to the 14-O position of oridonin appeared to increase the antiproliferative activity. The cytotoxicity of the derivatives with the substituent of acetyl at the 1-O position was better than those with the propylsulfonyl group and the 1-hydroxyl oxidated derivatives. Compounds 16 and 17 also had stronger anti-tumor activity in mice bearing H22 liver tumor than oridonin (45.9%) with the inhibition ratios of 69.9% and 61.2%, correspondingly.

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.