Addition of Cyanoethyl Groups to Ring a of Triterpenoids

Galaiko, Natalia V.; Толмачева, И. А.; Igosheva, E. V.; Savinova, Olga V.; Гришко, В. В.

doi:10.1007/s10600-018-2329-8

Cited by 4 publications

(5 citation statements)

References 23 publications

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“…To the best of our knowledge, except for 2a and 2c , the synthesis of the seco -A-triterpene derivatives has not been reported. Also, this methodology proved to be efficient and shorter than others. ,,,, …”

Section: Results and Discussionmentioning

confidence: 90%

“…Because of the few chemical active sites within the rigid skeleton of pentacyclic triterpenes, the A-ring expansion and ring opening of the triterpenoid nucleus to produce a less rigid skeleton have been performed on lupane-, oleanane-, and ursane-type triterpenes. Some strategies have been employed to obtain seco-triterpenes, including Beckmann fragmentation, 23,24,27,35 Schmidt reaction, 19 application of the taraxerane−oleanane rearrangement, 36 nucleophilic formylation and cyanation of conjugated enones, 30 and Baeyer−Villiger oxidation of the C-3 ketone. 22,25,26,28 Considering the importance of developing novel antiinflammatory agents, we explored the chemical modification in ring A of the anti-inflammatory natural triterpenes α-amyrin (1) and 3-epilupeol (2) by using the one-pot radical scission− oxidation process developed by Boto et al 37,38 So, treatment of α-amyrin 1 with (diacetoxyiodo)benzene (PhI(OAc) 2 ) and iodine (I 2 ) under irradiation with visible light at 26 °C afforded a separable mixture of 1a and 1b in 38% and 4% yield, respectively.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…Also, this methodology proved to be efficient and shorter than others. 19,23,26,30,36 Anti-inflammatory Activity. Effect of the seco-Triterpenes on Nitric Oxide Production, Pro-inflammatory Cytokines (IL-6 and TNF-α) Secretion, and NF-κB Activation.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Results and Discussionmentioning

confidence: 99%

“…seco -A-Triterpenoids obtained as derivatives from natural pentacyclic triterpenes have shown various pharmacological activities including cytotoxic, − antiviral, − antimalarial, inhibitors of protein tyrosine phosphatase, and anti-inflammatory. , Anti-inflammatory seco -A-triterpenoids also are produced in higher plants, although only in small amounts, and have shown anti-inflammatory activity in both in vivo and in vitro studies. , The anti-inflammatory activity shown by seco -A-pentacyclic triterpenes has motivated some research groups to focus their interest on the synthesis of chemical derivatives that can enhance this pharmacological activity. , These studies have shown that pentacyclic triterpenes modified in ring A increase the anti-inflammatory potency to 10 000 times in comparison with the starting triterpene …”

mentioning

confidence: 99%

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Synthesis, Biological Evaluation, and Molecular Docking Study of 3-Amino and 3-Hydroxy-seco A Derivatives of α-Amyrin and 3-Epilupeol as Inhibitors of COX-2 Activity and NF-kB Activation

et al. 2022

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In this study, a series of novel 3-seco-A derivatives of the natural triterpenes α-amyrin (1) and 3-epilupeol (2) were synthesized by a one-pot radical scission−oxidation procedure and evaluated in vitro and in vivo for their capacity to inhibit the inflammatory process. For the in vitro studies, the trans-4-hydroxy-L-proline methyl ester derivatives (1f and 2f) were consistently effective in inhibiting NO, IL-6, and TNF-α secretion, as well as inhibition of NF-κB activation, in RAW cells stimulated by LPS. The further in vivo anti-inflammatory study revealed that the trans-4-hydroxy-L-proline methyl ester derivatives (1f and 2f), together with 1g, were the most effective in inhibiting TPA-induced edema. Interestingly, the α-amyrin derivatives were the most potent inhibitors of COX-2, but inhibited COX-1 only to some extent. The hydroxyl derivative (1c) was selective for COX-2 inhibition (66.3 ± 1.1% at 17.5 μM) without affecting the COX-1 isoform and did not present toxicity. Molecular docking studies revealed that these compounds bind with their polar region in the cavity over Arg-120, and their lipophilic part is orientated to the HEM cofactor similarly to the natural substrate arachidonic acid in the catalytic site of COX-2. These results indicated that seco-A ursane derivatives could be considered promising candidates for the future development of selective NF-κB and COX-2 inhibitors.

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