Triterpenoid phthalimides as selective anti-cancer agents targeting mitochondrial apoptosis DOI Creative Commons
Anna N. Kazakova,

Ivo Frydrych,

Nikola Jakubcová

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117126 - 117126

Published: Dec. 10, 2024

Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, related derivatives. A total 55 new compounds prepared tested for in vitro cytotoxic activity against eight cancer cell lines two non-cancerous lines. Four with IC50 values 5 μM or lower selected further investigation. These induced apoptosis CCRF-CEM cells concentration-dependent manner, accompanied by mitochondrial depolarization altered expression key proteins involved apoptosis. The also disrupted DNA replication transcriptional activity. Modulation proliferation pathways, including PI3K/Akt STAT3, supported the antiproliferative potential these Considering their high cytotoxicity cells, 19, 26, 28, 30 have been identified as promising candidates development.

Language: Английский

Plant-derived terpenoids modulating cancer cell metabolism and cross-linked signaling pathways: an updated reviews DOI

Pratibha Pandey,

Meenakshi Verma, Gaurav Sanghvi

et al.

Naunyn-Schmiedeberg s Archives of Pharmacology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Language: Английский

Citations

0
Betulinic acid protects against lipopolysaccharide and ferrous sulfate-induced oxidative stress, ferroptosis, apoptosis, and neuroinflammation signaling relevant to Parkinson's Disease DOI
Shivam Kumar Pandey,

Anjuman Nanda,

Avtar Singh Gautam

et al.

Free Radical Biology and Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
HPMA Copolymers: A Versatile Platform for Targeted Peptide Drug Delivery DOI Creative Commons

Ya Li,

Liangda Xing,

Mingliang Zhu

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 596 - 596

Published: April 17, 2025

Peptide drugs have been broadly applied in cancer treatment and diagnosis due to their ability accurately identify biomarkers with good biocompatibility. However, clinical application is limited by protease degradation, which induces short circulation half-life, low bioavailability, high renal clearance. In recent years, delivery systems based on nanomaterial technology become an important strategy break through the bottleneck of peptide drug delivery. Among them, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers attracted much attention biocompatibility, hydrophilicity, immunogenicity. The molecular weight HPMA copolymer-peptide can circumvent clearance, significantly prolong time body, achieve accumulation microenvironment-triggered release synergistically EPR effects active targeting. This review introduces basic properties copolymers, including solubility, tunable chemical structure. applications tumor are discussed. deepens our understanding future development will provide more references for improving peptides simple copolymers.

Language: Английский

Citations

0
Multidimensional insights into squalene epoxidase drug development: in vitro mechanisms, in silico modeling, and in vivo implications DOI
Ahmed A. Allam, Hassan A. Rudayni, Noha Ahmed

et al.

Expert Opinion on Therapeutic Targets, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Squalene epoxidase (SQLE) is a pivotal enzyme in sterol biosynthesis, catalyzing the conversion of squalene to 2,3-oxidosqualene. Beyond its core role cholesterol homeostasis, SQLE implicated cancer, hypercholesterolemia, and fungal infections, positioning it as valuable therapeutic target. We conducted comprehensive literature search across primary databases gather vitro, silico, vivo evidence on SQLE. This review explores enzyme's structural functional features, including substrate specificity catalytic mechanisms, examines inhibitor interactions. Computational methods predict - dynamics, guiding drug design, while investigations clarify SQLE's metabolic disorders tumorigenesis. Challenges include resistance study discrepancies, but emerging technologies, such cryo-electron microscopy CRISPR editing, offer new avenues for deeper exploration. an underexplored yet promising target, with particular relevance oxidative stress, ferroptosis, gut microbiota research. Overcoming current barriers through advanced technologies multidisciplinary strategies could propel SQLE-targeted treatments into clinical practice, supporting precision medicine broader translational applications.

Language: Английский

Citations

0
Advancements in Betulinic Acid-Loaded Nanoformulations for Enhanced Anti-Tumor Therapy DOI Creative Commons
Ke Wang,

Jinlu Shang,

Chao Tao

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 14075 - 14103

Published: Dec. 1, 2024

Betulinic acid (BA) is a natural compound obtained from plant extracts and known for its diverse pharmacological effects, including anti-tumor, antibacterial, anti-inflammatory, antiviral, anti-atherosclerotic properties. Its potential in anti-tumor therapy has garnered considerable attention, particularly the treatment of breast, lung, liver cancers. However, clinical utility BA greatly hindered by poor water solubility, low bioavailability, off-target toxicity. To address these issues, researchers have developed various BA-loaded nanoformulations, such as nanoparticles, liposomes, micelles, nanofibers, aiming to improve solubility prolong plasma half-life, enhance targeting ability, thereby augmenting anti-cancer efficacy. In preparing this review, we conducted extensive searches well-known databases, PubMed, Web Science, ScienceDirect, using keywords like "betulinic acid", "nanoparticles", "drug delivery", "tumor", "cancer", covering literature 2014 2024. The review provides comprehensive overview recent advancements application nano-delivery systems offers insights into their future development prospects.

Language: Английский

Citations

2
Triterpenoid phthalimides as selective anti-cancer agents targeting mitochondrial apoptosis DOI Creative Commons
Anna N. Kazakova,

Ivo Frydrych,

Nikola Jakubcová

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117126 - 117126

Published: Dec. 10, 2024

Starting from benzyl 30-oxobetulinate and 30-oxobetulin diacetate, substituted dienes were synthesized subjected to Diels-Alder reaction, yielding a variety of triterpenoid phthalates, phthalimides, related derivatives. A total 55 new compounds prepared tested for in vitro cytotoxic activity against eight cancer cell lines two non-cancerous lines. Four with IC50 values 5 μM or lower selected further investigation. These induced apoptosis CCRF-CEM cells concentration-dependent manner, accompanied by mitochondrial depolarization altered expression key proteins involved apoptosis. The also disrupted DNA replication transcriptional activity. Modulation proliferation pathways, including PI3K/Akt STAT3, supported the antiproliferative potential these Considering their high cytotoxicity cells, 19, 26, 28, 30 have been identified as promising candidates development.

Language: Английский

Citations

1