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.
Design, synthesis, and discovery of ocotillol-type amide derivatives as orally available modulators of P-glycoprotein-mediated multidrug resistance
Ren, Qianwen,Yang, Gangqiang,Guo, Mengqi,Guo, Jingwen,Li, Yang,Lu, Jing,Yang, Qing,Tang, Hanhan,Li, Yi,Fang, Xiaojuan,Sun, Yixiao,Qi, Jia Grace,Tian, Jingwei,Wang, Hongbo
, p. 118 - 130 (2019)
Multidrug resistance (MDR) is a major cause of failure in cancer treatment, in which the overexpression of P-glycoprotein (Pgp) plays a crucial role. Herein, a novel class of ocotillol-type amide derivatives has been designed, synthesized, and evaluated for their ability to reverse MDR. The structure-activity relationship of the reversal activity was analyzed. Ten compounds showed promising chemo-reversal ability, among which the 24R-ocotillol-type amide derivative 6c with an N-Boc-hexanoyl unit exhibited the most potency in reversing paclitaxel resistance in KBV cells. Compound 6c could inhibit Pgp-mediated rhodamine123 efflux function via stimulating Pgp-ATPase activity and exhibited high binding affinity with Pgp in molecular docking studies. Importantly, compound 6c enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors in nude mice after oral administration. These results indicate that ocotillol-type amide derivatives are promising lead compounds for overcoming MDR in cancer.
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.].
Design, synthesis and biological evaluation of novel ocotillol-type triterpenoid derivatives as antibacterial agents
Shao, Xiao,Zhang, Shengyu,Zhou, Yunyun,Zeng, Xianming,Zhou, Zhiwen
, p. 27 - 38 (2020/03/17)
A new series of hydrophilic ocotillol-type triterpenoid derivatives have been synthesized and evaluated for their in vitro antibacterial activity against Gram-positive and Gram-negative bacteria. Among which, compounds 9, 10, 11c, 12c, 13a-d and 14a-d displayed potent antibacterial activity against Gram-positive bacteria with MIC values of 1-16 μg/mL. Furthermore, additional testing against MRSA USA300 demonstrated that compounds 9, 13b, 13c and 14c also possess good antibacterial activity with MIC values of 2-8 μg/mL. The bactericidal effects revealed that compounds 9, 13b and 13c displayed directly bactericidal activity against B. subtilis and MRSA USA300 with MBC values of 2-16 μg/mL. The subsequent synergistic activity assay showed that compounds 13b and 13c could enhance the susceptibility of MRSA USA300 and B. subtilis to kanamycin and chloramphenicol (FICI 0.5). Compounds 13b and 13c were then evaluated for their cytotoxicity and displayed low toxicity at their antibacterial MICs. The optimized structure-activity relationship was also concluded.
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.
With antibacterial activity (20 S, 24 R) - ocotillol-type Ginseng saponin derivatives, their preparation and use
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Paragraph 0092-0094, (2017/09/01)
The invention relates to the fields of organic synthesis and pharmaceutical chemistry, in particular to a (20S, 24R)-ocotillol type ginsenoside derivative having represented in a structural formula (I). The invention further discloses a reparation method of the (20S, 24R)-ocotillol type ginsenoside derivative, pharmaceutical compositions containing the derivative and anti-bacterial and anti-infection application.
Synthesis and antibacterial evaluation of novel hydrophilic ocotillol-type triterpenoid derivatives from 20(S)-protopanaxadiol
Bi, Yi,Ma, Cong,Zhou, Zhiwen,Zhang, Tingting,Zhang, Hengyuan,Zhang, Xiaochen,Lu, Jing,Meng, Qingguo,Lewis, Peter J.,Xu, Jinyi
, p. 356 - 368 (2015/09/22)
Triterpenoid saponins are involved in plant defense systems to inhibit bacterial invasion. A new series of hydrophilic ocotillol-type triterpenoid derivatives 5-26 have been synthesized with antibacterial activity against Gram-positive bacteria, including a community associated methicillin-resistant Staphylococcus aureus (CA-MRSA; strain USA300). From this series, compounds 6 and 15 were found to be the most active, both with MIC values of 2 μg/mL against B. subtilis 168 and 8 μg/mL against S. aureus USA300, respectively. Furthermore, subsequent assays showed that compounds 6 and 15 displayed strong synergistic effects at sub-MIC levels against both S. aureus USA300 and B. subtilis 168 when combined with two commercial antibiotics, kanamycin and chloramphenicol. Preliminary structure-activity relationship studies were also performed.
Synthesis and biological evaluation of novel ocotillol-type triterpenoid derivatives as antibacterial agents
Zhou, Zhiwen,Ma, Cong,Zhang, Hengyuan,Bi, Yi,Chen, Xia,Tian, Hua,Xie, Xiaoni,Meng, Qingguo,Lewis, Peter John,Xu, Jinyi
, p. 444 - 453 (2013/10/01)
A novel class of ocotillol-type triterpenoid derivatives have been synthesized and evaluated for their in vitro antibacterial activity against several representative pathogenic bacterial strains. Compounds 20(S)-protopanaxadiol (PPD), 3, 5, 16 and 24 exhibited potent antibacterial activity against Gram-positive bacteria. Compounds 3 and 5 also displayed promising antibacterial activity against a community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA; strain USA300). Furthermore, compounds PPD, 3 and 16 combined with two commercially available antibiotics kanamycin and chloramphenicol showed strong synergistic inhibitory effects at their sub-MIC concentrations against S. aureus USA300 and Bacillus subtilis 168. Additionally, cytotoxic activity assay showed that the compounds tested did not affect cell viability of the human epithelial kidney (HEK-293) and human cervical (HeLa) cells at their MICs.
GLYCOSYLATION OF TRITERPENOIDS OF THE DAMMARANE SERIES. II. 12,25-DI-O- AND 3,12,25-TRI-O-GLUCOPYRANOSIDES OF 20(S),24(R)-EPOXYDAMMARANE-3α-12β,25-TRIOL AND ITS 3-EPIMER
Atopkina, L. N.,Uvarova, N. I.
, p. 254 - 257 (2007/10/02)
On the glycosylation of 20(S),24(R)-epoxydammarane-3α,12β,25-triol (I), its 3-O-acetyl derivative (II), and its 3-epimer with α-acetobromoglucose under the conditions of Helferich's modification and with glucose tert-butyl orthoacetate under the condition
