Triterpenoids as Reactive Oxygen Species Modulators of Cell Fate

Ling, Taotao; Boyd, Lucinda; Rivas, Fátima

doi:10.1021/acs.chemrestox.1c00428

Cited by 22 publications

(11 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, considering the current data, the recorded decrease of State 2 CI and State 4 CI+CII may suggest that compounds 1 and 2 can increase mitochondrial ROS production; compound 3 did not produce evidence of such an effect. Natural triterpenoids have been characterized as ROS modulators, thus offering the possibility to generate derivatives with high selectivity on ROS regulation [ 50 ]. The stimulatory activity of compounds 1 and 2 on ROS generation may partly explain their apoptotic activity in melanoma cells.…”

Section: Discussionmentioning

confidence: 99%

Novel Triterpenic Acid—Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents

Mioc

Prodea

et al. 2022

IJMS

View full text Add to dashboard Cite

Pentacyclic triterpenes, such as betulinic, ursolic, and oleanolic acids are efficient and selective anticancer agents whose underlying mechanisms of action have been widely investigated. The introduction of N-bearing heterocycles (e.g., triazoles) into the structures of natural compounds (particularly pentacyclic triterpenes) has yielded semisynthetic derivatives with increased antiproliferative potential as opposed to unmodified starting compounds. In this work, we report the synthesis and biological assessment of benzotriazole esters of betulinic acid (BA), oleanolic acid (OA), and ursolic acid (UA) (compounds 1–3). The esters were obtained in moderate yields (28–42%). All three compounds showed dose-dependent reductions in cell viability against A375 melanoma cells and no cytotoxic effects against healthy human keratinocytes. The morphology analysis of treated cells showed characteristic apoptotic changes consisting of nuclear shrinkage, condensation, fragmentation, and cellular membrane disruption. rtPCR analysis reinforced the proapoptotic evidence, showing a reduction in anti-apoptotic Bcl-2 expression and upregulation of the pro-apoptotic Bax. High-resolution respirometry studies showed that all three compounds were able to significantly inhibit mitochondrial function. Molecular docking showed that compounds 1–3 showed an increase in binding affinity against Bcl-2 as opposed to BA, OA, and UA and similar binding patterns compared to known Bcl-2 inhibitors.

show abstract

Section: Discussionmentioning

confidence: 99%

Novel Triterpenic Acid—Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents

Mioc

Prodea

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…However, our findings indicated that this assumption was incorrect because the hydroxyl group in the same position on sidrin was found to form an epoxy ring with C-2, and the compound proved effective. In addition, recent studies have reported that the cytotoxic activity depends on the type of substitution on C-3 and C-28, not on the presence of free hydroxyl on C-3 or the free carboxylic group on C-28 ( Kommeraet al, 2010 , Kozubeket al, 2021 , Linget al, 2022 , Nistoret al, 2022 ). Moreover, the cytotoxic activity, but with decreased selectivity, was increased by the oxidation of this hydroxyl group.…”

Section: Discussionmentioning

confidence: 99%

Isolation and identification of novel selective antitumor constituents, sidrin and sidroside, from Zizyphus spina-christi

Mostafa

Khojah

Ohta

2023

Saudi Pharmaceutical Journal

View full text Add to dashboard Cite

“…Triterpenes such as lupane-type triterpenes can modulate a cascade of events through processes mediated by ROS [ 48 ]. They have membranotropic activity, increasing mitochondrial membrane permeability and promoting cell death by apoptosis [ 49 , 50 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Lupane Triterpene Derivatives Improve Antiproliferative Effect on Leukemia Cells through Apoptosis Induction

et al. 2022

View full text Add to dashboard Cite

Leukemia is one of the most frequent types of cancer. No effective treatment currently exists, driving a search for new compounds. Simple structural modifications were made to novel triterpenes isolated from Phoradendron wattii. Of the three resulting derivatives, 3α-methoxy-24-hydroxylup-20(29)-en-28-oic acid (T1m) caused a decrease in the median inhibitory concentration (IC50) on the K562 cell line. Its mode of action was apparently apoptosis, ROS generation, and loss of mitochondrial membrane potential (MMP). Molecular docking analysis showed T1m to produce lower binding energies than its precursor for the Bcl-2 and EGFR proteins. Small, simple, and viable modifications to triterpenes can improve their activity against leukemia cell lines. T1m is a potentially promising element for future research. Clarifying the targets in its mode of action will improve its applicability.

show abstract

Triterpenoids as Reactive Oxygen Species Modulators of Cell Fate

Cited by 22 publications

References 81 publications

Novel Triterpenic Acid—Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents

Novel Triterpenic Acid—Benzotriazole Esters Act as Pro-Apoptotic Antimelanoma Agents

Isolation and identification of novel selective antitumor constituents, sidrin and sidroside, from Zizyphus spina-christi

Lupane Triterpene Derivatives Improve Antiproliferative Effect on Leukemia Cells through Apoptosis Induction

Contact Info

Product

Resources

About