Ring-Modified Triterpene Derivatives as Potential Pharmacological Active Compounds

Ulici, Alexandra; Milan, Andreea; Mioc, Marius; Ghiulai, Roxana; Racoviceanu, Roxana; Şoica, Codruţa

doi:10.35995/tmj20200207

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…Betulinic acid (BA; 3β-hydroxy-lup-20 (29)-en-28-oic acid; Figure 3 ) is a widespread lupane-type pentacyclic triterpene that has been the subject of numerous studies highlighting its biological activities in various pathologies such as diabetes, microbial and viral infections, inflammatory diseases, and numerous types of cancer, among others [ 52 ]. In order to improve its bioavailability and enhance its therapeutic effect, a large number of chemical modulations have been conducted, mostly in the C-3, C-28, and C-30 positions ( Figure 3 ) [ 53 ], but also ring modifications in the BA main scaffold [ 54 ].…”

Section: Betulinic Acidmentioning

confidence: 99%

Semisynthetic Derivatives of Pentacyclic Triterpenes Bearing Heterocyclic Moieties with Therapeutic Potential

et al. 2022

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Medicinal plants have been used by humans since ancient times for the treatment of various diseases and currently represent the main source of a variety of phytocompounds, such as triterpenes. Pentacyclic triterpenes have been subjected to numerous studies that have revealed various biological activities, such as anticancer, antidiabetic, anti-inflammatory, antimicrobial, and hepatoprotective effects, which can be employed in therapy. However, due to their high lipophilicity, which is considered to exert a significant influence on their bioavailability, their current use is limited. A frequent approach employed to overcome this obstacle is the chemical derivatization of the core structure with different types of moieties including heterocycles, which are considered key elements in medicinal chemistry. The present review aims to summarize the literature published in the last 10 years regarding the derivatives of pentacyclic triterpenes bearing heterocyclic moieties and focuses on the biologically active derivatives as well as their structure–activity relationships. Predominantly, the targeted positions for the derivatization of the triterpene skeleton are C-3 (hydroxyl/oxo group), C-28 (hydroxyl/carboxyl group), and C-30 (allylic group) or the extension of the main scaffold by fusing various heterocycles with the A-ring of the phytocompound. In addition, numerous derivatives also contain linker moieties that connect the triterpenic scaffold with heterocycles; one such linker, the triazole moiety, stands out as a key pharmacophore for its biological effect. All these studies support the hypothesis that triterpenoid conjugates with heterocyclic moieties may represent promising candidates for future clinical trials.

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Section: Betulinic Acidmentioning

confidence: 99%

Semisynthetic Derivatives of Pentacyclic Triterpenes Bearing Heterocyclic Moieties with Therapeutic Potential

et al. 2022

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“…One well-known drawback of these phytocompounds is the reduced bioavailability that limits their use. To overcome this limitation, pentacyclic triterpenoids have been subjected to numerous derivatizations, which led to some derivatives with superior activity compared to parent compounds [ 7 ]. For instance, Spivak et al [ 8 ] synthesized a series of cationic conjugates of betulin and several triterpenic acids, which specifically targeted the mitochondria of several cancer cells in vitro, showing a significant increase in cytotoxicity (more than 100 fold for the betulinic acid derivative compared to betulinic acid) compared to natural compounds.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

Mioc

Milan

Malița

et al. 2022

IJMS

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Triterpenic acids are phytocompounds with a widespread range of biological activities that have been the subject of numerous in vitro and in vivo studies. However, their underlying mechanisms of action in various pathologies are not completely elucidated. The current review aims to summarize the most recent literature, published in the last five years, regarding the mechanism of action of three triterpenic acids (asiatic acid, oleanolic acid, and ursolic acid), corelated with different biological activities such as anticancer, anti-inflammatory, antidiabetic, cardioprotective, neuroprotective, hepatoprotective, and antimicrobial. All three discussed compounds share several mechanisms of action, such as the targeted modulation of the PI3K/AKT, Nrf2, NF-kB, EMT, and JAK/STAT3 signaling pathways, while other mechanisms that proved to only be specific for a part of the triterpenic acids discussed, such as the modulation of Notch, Hippo, and MALAT1/miR-206/PTGS1 signaling pathway, were highlighted as well. This paper stands as the first part in our literature study on the topic, which will be followed by a second part focusing on other triterpenic acids of therapeutic value.

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New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design

Казакова

Racoviceanu

Petrova

et al. 2021

IJMS

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Twenty lupane type A-ring azepano-triterpenoids were synthesized from betulin and its related derivatives and their antitubercular activity against Mycobacterium tuberculosis, mono-resistant MTB strains, and nontuberculous strains Mycobacterium abscessus and Mycobacterium avium were investigated in the framework of AToMIc (Anti-mycobacterial Target or Mechanism Identification Contract) realized by the Division of Microbiology and Infectious Diseases, NIAID, National Institute of Health. Of all the tested triterpenoids, 17 compounds showed antitubercular activity and 6 compounds were highly active on the H37Rv wild strain (with MIC 0.5 µM for compound 7), out of which 4 derivatives also emerged as highly active compounds on the three mono-resistant MTB strains. Molecular docking corroborated with a machine learning drug-drug similarity algorithm revealed that azepano-triterpenoids have a rifampicin-like antitubercular activity, with compound 7 scoring the highest as a potential M. tuberculosis RNAP potential inhibitor. FIC testing demonstrated an additive effect of compound 7 when combined with rifampin, isoniazid and ethambutol. Most compounds were highly active against M. avium with compound 14 recording the same MIC value as the control rifampicin (0.0625 µM). The antitubercular ex vivo effectiveness of the tested compounds on THP-1 infected macrophages is correlated with their increased cell permeability. The tested triterpenoids also exhibit low cytotoxicity and do not induce antibacterial resistance in MTB strains.

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Ring-Modified Triterpene Derivatives as Potential Pharmacological Active Compounds

Cited by 3 publications

References 27 publications

Semisynthetic Derivatives of Pentacyclic Triterpenes Bearing Heterocyclic Moieties with Therapeutic Potential

Semisynthetic Derivatives of Pentacyclic Triterpenes Bearing Heterocyclic Moieties with Therapeutic Potential

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part I)

New Investigations with Lupane Type A-Ring Azepane Triterpenoids for Antimycobacterial Drug Candidate Design

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