219550-95-5

Upstream product

• 853734-24-4 28-benzyl 3,23-O-isopropylidene hederagenate 
• 60684-64-2 3β,23-O-isopropylidene-3β,23-dihydroxyolean-12-en-28-oic acid 
• 465-99-6 hedaragenin 
• 100-39-0 benzyl bromide 

Downstream Products

• 853734-25-5 2,3,4-tri-O-acetyl-α-L-rhamnopyranosyl-(1->2)-5-O-acetyl-3,4-di-O-benzyl-L-arabinose(open)-[(1R)->3,23]-28-benzyl hederagenate 
• 1025795-44-1 benzyl 3-oxo-23-hydroxyolean-12-en-28-oate 
• 466-01-3 hederagonic acid 

Relevant academic research and scientific papers

Hederagenin as a triterpene template for the development of new antitumor compounds

In this study, a series of novel C-28 esters and amides derivatives of hederagenin (He) were designed and synthesized in attempt to develop potent antitumor agents. Their structures were confirmed by MS, IR, 1H NMR and 13C NMR spectroscopic analyses and their cytotoxic activities were screened in SRB assays using a panel of six human cancer cell lines. Although most of the compounds displayed moderate to high levels of cytotoxic activity they were all more potent than the natural product He. The most active compounds had either an ethylpyrimidinyl (27) or an ethylpyrrolidinyl (28) substituent, with EC50 in the range of 1.1-6.5 μM for six human cancer cell lines. Notably, this corresponds to an approximately 30-fold times greater potency than He.

Synthesis and biological evaluation of novel H6 analogues as drug resistance reversal agents

Hederagenin is a naturally occurring pentacyclic triterpenoids compound with multiple pharmacological activities. We recently showed that H6, a synthetic derivative of hederagenin, could enhance the anticancer activity of paclitaxel in drug-resistant cells in vitro and in vivo, but showed poor solubility. With the aim of improving the drug resistant reversal activity of H6, here we designed and synthesized a series of novel H6 analogues. Our results showed that compound 10 at the concentration of 5 μM significantly enhanced the cytotoxicity of paclitaxel to drug-resistant KBV cells and sensitized cells to paclitaxel in arresting cells in G2/M phase and inducing apoptosis. We found that compound 10 might block the drug efflux of P-gp via stimulating P-gp ATPase activity. Importantly, compound 10 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors. Finally, we summarized a preliminary structure-activity relationship of hederagenin by the drug resistant reversal activity of H6 analogues in vitro and compound 10 and H6 in vivo. This study highlights the importance of nitrogen-containing derivatives of hederagenin C-28 in the development of novel drug resistance reversal agents.

Highly potent anti-leishmanial derivatives of hederagenin, a triperpenoid from Sapindus saponaria L.

Leishmaniasis is a neglected tropical disease (NTDs), endemic in 88 countries that affect more than 12 million people. Current drugs are limited due to their toxicity, development of biological resistance, length of treatment and high cost. Thus, the search for new effective and less toxic treatments is an urgent need. In this study, we report the synthesis of 3 new amide derivatives of hederagenin (22–24) with yields between 70% and 90%, along with 57 other derivatives of hederagenin (1–21, 25–60) carrying different groups at C-28 previously reported by our group, and the results of their in?vitro ability to inhibit the growth of Leishmania infantum. Some derivatives (3, 4, 44, 49 and 52), showed activity at micromolar level and low toxicity against BGM and HepG2 cells. Moreover, the ability of hederagenin derivatives 3 (IC50?=?9.7?μM), 4 (12?μM), 44 (11?μM) and 49 (2?μM), to prevent proliferation of intracellular amastigote forms of L.?infantum and their higher selectivity index and low toxicity compared to commercial positive drug control of choice (potassium antimonyl tartrate trihydrate) (IC50?=?80?μM, SI?=?0.1), make these compounds promising candidates for the treatment of leishmaniasis.

Design, synthesis, and biological evaluation of hederagenin derivatives with improved aqueous solubility and tumor resistance reversal activity

Multidrug resistance (MDR) has become a major obstacle to malignancies treatment by chemotherapeutic drugs, therefore, it is important to develop MDR reversal agents with high activity. We have previously found that the hederagenin (HD) derivative HBQ showed good tumor MDR reversal activity in vitro and in vivo but had poor solubility. In this study, to enhance the aqueous solubility and tumor MDR reversal activity of HBQ, three series of HD derivatives were designed and synthesized. Nitrogen-containing heterocyclic-substituted, PEGylated, and ring-A substituted derivatives significantly reversed the MDR phenotype of KBV (multidrug-resistant oral epidermoid carcinoma) cells toward paclitaxel at a concentration of 10 μM in MTT assays. The PEGylated derivatives 10c–10e had increased aqueous solubility compared with HBQ by 18–657 fold, while maintaining tumor MDR reversal activity. The most in vitro active compound 10c possessed good chemical stability to an esterase over 24 h and enhanced the sensitivity of KBV cells to paclitaxel and vincristine with IC50 values of 4.58 and 0.79 nM, respectively. Mechanism studies indicated that compound 10c increased the accumulation of P-glycoprotein (P-gp) substrates rhodamine 123 and Flutax1 in KBV cells and MCF-7T (paclitaxel-resistant breast carcinoma) cells, that is to say, compound 10c exerted the reversal effect of tumor MDR by inhibiting the efflux function of P-gp. Finally, the structure–activity relationships were further investigated by analyzing the relationship between structure and tumor MDR reversal activity of HD derivatives. This study highlights the potential of PEGylated HD derivatives such as compound 10c for the development of tumor MDR reversal agents and provides information for the further improvement of the aqueous solubility and tumor MDR reversal activity of HD derivatives in the future.

Hederagenin polyethylene glycol derivative and preparation method thereof

The invention relates to the field of organic synthesis and medicinal chemistry, in particular to a hederagenin polyethylene glycol derivative with a novel structure and a preparation method of the hederagenin polyethylene glycol derivative. The compound disclosed by the invention is novel in structural type, improved in water solubility and excellent in tumor drug resistance reversion activity. The invention further provides a pharmaceutical composition for treating oral epithelial cancer, gastric cancer, lung cancer, cervical cancer, breast cancer or colon cancer and the like by being combined with clinically common anti-tumor drugs.

Hederagenin C-28-site polyethylene glycol modified derivative and preparation method thereof

The invention discloses a hederagenin C-28-site polyethylene glycol modified derivative and a preparation method thereof. The derivative disclosed by the invention comprises N-(23-hydroxyl oleanole-12-ene-28-acyl-[3, 2-b] pyrazine)-4-aminobutyric acid diglycol ester, N-(23-hydroxyl oleanole-12-ene-28-acyl-[3, 2-b] pyrazine)-4-aminobutyric acid triethylene glycol ester, and the like. The hederagenin polyethylene glycol modified derivative and the pharmaceutically acceptable salt thereof have excellent tumor drug resistance reversal activity and relatively high water solubility, so that the drug resistance reversal activity and the water solubility of the obtained hederagenin derivative are remarkably improved, and the hederagenin derivative has druggability.

Synthesis of Anemoclemosides A and B, Two Saponins Isolated from Anemoclema glaucifolium

Steroidal and triterpenoid saponins are attractive for their wide-ranging pharmacological properties. The triterpenoid saponins Anemoclemoside A and B are root constituents of the Chinese folk medicinal plant Anemoclema glaucifolium (Ranunculaceae). Both

An investigation of the antileishmanial properties of semi-synthetic saponins

Leishmaniasis is a neglected tropical disease caused by insect-vector borne protozoan parasites of the, Leishmania species. Whilst infection threatens and affects millions of the global poor, vaccines are absent and drug therapy limited. Extensive efforts have recently been made to discover new leads from small molecule synthetic compound libraries held by industry; however, the number of new chemical entities identified and entering development as anti-leishmanials has been very low. This has led to increased interest in the possibility of discovering naturally derived compounds with potent antileishmanial activity which may be developed towards clinical applications. Plant-derived triterpenoid and steroidal saponins have long been considered as anti-microbials and here we describe an investigation of a library of 137 natural (9) and semi-synthetic saponins (128) for activity against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. The triterpenoid sapogenin, hederagenin, readily obtained in large quantities from Hedera helix (common ivy), was converted into a range of 128 derivatives. These semi-synthetic compounds, as well as saponins isolated from ivy, were examined with a phenotypic screening approach to identify potent and selective anti-leishmanial hits. This led to the identification of 12 compounds, including the natural saponin gypsogenin, demonstrating high potency (ED50 10. Whilst this was not active in an infected cell model, the anti-leishmanial properties of hederagenin-derivatives have been demonstrated, and the possibility of improving the selectivity of natural hederagenin through chemical modification has been established. This journal is

Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity

In an attempt to arrive at a more potent cytotoxic agent than the parent compound α-hederagenin (H), 24 α-hederagenin derivatives (5–8, 11–24, 27–28, 31–32, and 35–36) were synthesized in a concise and efficient strategy and screened for in vitro cytotoxicity against the human cancer cell lines MKN45 and KB. Among these compounds, the polyamine derivative 15 exhibited more potency than the parent compound with IC50 values in the range of 4.22 μM–8.05 μM. Compound 15 increased Bax/bcl-2 ratio that disrupted the mitochondrial potential and induced apoptosis. Therefore, the present studies highlight the importance of polyamine derivatives of α-hederagenin in the discovery and development of novel anticancer agents.

Alpha-helexin derivatives, and preparation method and application thereof

The invention relates to the fields of organic synthesis and pharmaceutical chemistry, and particularly discloses novel-structure alpha-helexin derivatives. The invention also discloses a preparation method of the triterpene saponin derivatives, a pharmaceutical composition containing the derivatives, and application of the derivatives in resisting neoplastic diseases.