25279-15-6Relevant articles and documents
Synthesis and Structure-Activity Relationship of Pyxinol Derivatives as Novel Anti-Inflammatory Agents
Bi, Wenjing,Cui, Yetong,Fan, Huaying,Fang, Xiaojuan,Gao, Hongyan,Gao, Meng,Sun, Yixiao,Tang, Hanhan,Wang, Conghui,Yang, Gangqiang,Yu, Hui,Zhang, Leiming
, p. 457 - 463 (2020)
Pyxinol, the main metabolite of 20S-protopanaxadiol in human liver, was chosen as a novel skeleton for the development of anti-inflammatory agents. Pyxinol derivatives modified at C-3, C-12, or C-25 and selected stereoisomers were designed, prepared, and investigated for in vitro anti-inflammatory activities. Structure-activity relationship (SAR), focused on skeleton, was analyzed based on their ability to inhibit lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis. The preliminary SAR results signified that the biological activity of the pyxinol derivatives is largely dependent on the R/S stereochemistry of pyxinol skeleton and the hydroxy at C-3 is a modifiable position. Among the tested compounds, the 3-oximinopyxinol (4a) exhibited the most potent NO-inhibitory activity and was even comparable to the steroid drug. Furthermore, compound 4a also significantly decreased LPS-induced TNF-α and IL-6 synthesis and iNOS and COX-2 expressions via the NF-κB pathway. This study proves that pyxinol is an interesting skeleton for anti-inflammatory drug discovery.
Synthesis and biological evaluation of (20S,24R)-epoxy-dammarane-3β,12β,25-triol derivatives as α-glucosidase and PTP1B inhibitors
Chen, Ji-Jun,Geng, Chang-An,Li, Tian-Ze,Liu, Pei,Yang, Xiao-Tong
, p. 350 - 367 (2022/01/19)
The dammarane triterpenoid (20S,24R)-epoxy-dammarane-3β,12β,25-triol obtained from Cyclocarya paliurus in our previous study showed inhibitory activity on α-glucosidase in vitro with an inhibitory ratio of 32.2% at the concentration of 200 μM. In order to reveal the structure-activity relationships (SARs) and get more active compounds, 42 derivatives of (20S,24R)-epoxy-dammarane-3β,12β,25-triol were synthesized by chemical modification on the hydroxyls (C-3 and C-12), rings A and E, and assayed for their α-glucosidase and PTP1B inhibitory activities. Two compounds (8, 26) increased activity against α-glucosidase, and four compounds (8, 15, 26, 42) significantly inhibited PTP1B. It was noted that compounds 8 and 26 could inhibit both α-glucosidase and PTP1B as dual-target inhibitors with IC50 values of 489.8, 467.7 μM (α-glucosidase) and 319.7, 269.1 μM (PTP1B). Compound 26 was revealed to be a mix-type inhibitor on α-glucosidase and a noncompetitive-type inhibitor on PTP1B based on enzyme kinetic study. Furthermore, compound 42 could selectively inhibited PTP1B as a mix-type inhibitor with IC50 value of 134.9 μM, which was 2.5-fold higher than the positive control, suramin sodium (IC50 339.0 μM), but not inhibit α-glucosidase. [Figure not available: see fulltext.].
Ocotillol-type sapogenin derivatives with tumor drug resistance reversal activity and preparation method and application thereof
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Paragraph 0044; 0049, (2019/01/08)
The invention relates to a kind of ocotillol-type sapogenin derivatives and medicine compounds containing the ocotillol-type sapogenin derivatives and preparation method and tumor drug resistance reversal application thereof. According to the ocotillol-type sapogenin derivatives, through a result obtained on a tumor drug resistance oral epidermoid carcinoma cell strain, the prepared ocotillol-typesapogenin derivatives have good drug resistance reversal activity separately, and are obviously better than ocotillol-type sapogenin; meanwhile, products have good gastrointestinal tract stability and good drug applicability, namely characteristics which compounds disclosed in the prior art do not have.