Enhanced Cytotoxicity and Antimelanoma Activity of Novel Semisynthetic Derivatives of Betulinic Acid with Indole Conjugation DOI Creative Commons
Adelina Lombrea, Claudia Watz, Larisa Bora

et al.

Plants, Journal Year: 2023, Volume and Issue: 13(1), P. 36 - 36

Published: Dec. 21, 2023

The prevalence and severity of skin cancer, specifically malignant melanoma, among Caucasians remains a significant concern. Natural compounds from plants have long been explored as potential anticancer agents. Betulinic acid (BI) has shown promise in its therapeutic properties, including effects. However, limited bioavailability hindered medicinal applications. To address this issue, two recently synthesized semisynthetic derivatives, N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) N-(2,3-indolo-betulinoyl)glycylglycine (BA2), were compared with previously reported N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic (BA4), BI. These evaluated for their effects on murine melanoma cells (B164A5) using various vitro assays. introduction an indole framework at the C2 position BI resulted increased cytotoxicity. Furthermore, cytotoxicity compound BA4 was enhanced by conjugating carboxylic group amino residue. BA2 BA3, glycine glycylglycine residues C28, exhibited approximately 2.20-fold higher inhibitory activity to BA4. safety assessment human keratinocytes (HaCaT) revealed that concentrations up 10 µM slightly reduced cell viability, while 75 lower viability rates. LDH leakage assays confirmed membrane damage B164A5 when exposed tested compounds. BA3 highest release, indicating strong NR assay dose-dependent lysosome disruption BA1, BA2, showing most cytotoxic Scratch demonstrated concentration-dependent inhibition migration, being effective. Hoechst 3342 staining induced apoptosis, necrosis concentrations, confirming anti-melanoma properties. In conclusion, derivatives BI, particularly show candidates further research developing effective anti-cancer therapies.

Language: Английский

Conjugation of Triterpenic Acids with 3-Aminoquinuclidine Moiety: An Approach to Acetylcholinesterase Mixed or Uncompetitive Type Inhibitors DOI Creative Commons
Anastasiya V. Petrova, Há Thi Nguyen, Irina V. Zueva

et al.

Molecules, Journal Year: 2024, Volume and Issue: 30(1), P. 95 - 95

Published: Dec. 29, 2024

Alzheimer’s disease (AD) poses a significant public health issue. Despite the fact that today there are several methods of maintenance therapy, one most widely used is designed to correct deficiency acetylcholine. In search for new potential inhibitors cholinesterase enzymes, eight derivatives 3-oxo- or 2,3-indolo-triterpenic acid conjugated with amino-quinuclidine bicyclic cores were and synthesized. Then, obtained compounds screened in Ellman’s assays their ability inhibit acetylcholinesterase enzyme, each active compounds, type inhibition was determined. The results demonstrate dependence activity on triterpenoid structure substituents. best ursolic observed 3-oxoamide 8, an IC50 value 0.43 µM, acting as mixed-type inhibitor. turn, oleanane type, amide indole unit A ring 11 exhibited 0.47 µM (while ursane-type analog weakly active) led uncompetitive inhibition. Thus, 3-amidoquinuclidine-triterpenoids conjugates could be considered novel different mechanism action.

Language: Английский

Citations

0
Enhanced Cytotoxicity and Antimelanoma Activity of Novel Semisynthetic Derivatives of Betulinic Acid with Indole Conjugation DOI Creative Commons
Adelina Lombrea, Claudia Watz, Larisa Bora

et al.

Plants, Journal Year: 2023, Volume and Issue: 13(1), P. 36 - 36

Published: Dec. 21, 2023

The prevalence and severity of skin cancer, specifically malignant melanoma, among Caucasians remains a significant concern. Natural compounds from plants have long been explored as potential anticancer agents. Betulinic acid (BI) has shown promise in its therapeutic properties, including effects. However, limited bioavailability hindered medicinal applications. To address this issue, two recently synthesized semisynthetic derivatives, N-(2,3-indolo-betulinoyl)diglycylglycine (BA1) N-(2,3-indolo-betulinoyl)glycylglycine (BA2), were compared with previously reported N-(2,3-indolo-betulinoyl)glycine (BA3), 2,3-indolo-betulinic (BA4), BI. These evaluated for their effects on murine melanoma cells (B164A5) using various vitro assays. introduction an indole framework at the C2 position BI resulted increased cytotoxicity. Furthermore, cytotoxicity compound BA4 was enhanced by conjugating carboxylic group amino residue. BA2 BA3, glycine glycylglycine residues C28, exhibited approximately 2.20-fold higher inhibitory activity to BA4. safety assessment human keratinocytes (HaCaT) revealed that concentrations up 10 µM slightly reduced cell viability, while 75 lower viability rates. LDH leakage assays confirmed membrane damage B164A5 when exposed tested compounds. BA3 highest release, indicating strong NR assay dose-dependent lysosome disruption BA1, BA2, showing most cytotoxic Scratch demonstrated concentration-dependent inhibition migration, being effective. Hoechst 3342 staining induced apoptosis, necrosis concentrations, confirming anti-melanoma properties. In conclusion, derivatives BI, particularly show candidates further research developing effective anti-cancer therapies.

Language: Английский

Citations

1