Novel Sulfonyl-Substituted Tetrandrine Derivatives for Colon Cancer Treatment by Inducing Mitochondrial Apoptosis and Inhibiting PI3K/AKT/mTOR Pathway DOI
Jie Ling, Xiao Li, Maolin Wang

et al.

Published: Jan. 1, 2023

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide sulfonate TET derivatives were designed, synthesized, evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, β-unsaturated carbonyl group exhibited most potent against all tested cell lines (including Hela, HCT116, HepG2, MCF-7, SHSY5Y), as well negligible normal LO2 HEK293. Additionally, effectively inhibited HCT116 CT26 in vitro increased proportion G2/M phase, activated mitochondrial apoptosis pathway, induced colon cancer by suppressing PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that is potentially bound to residues stronger binding affinity than TET. Ultimately, dramatically suppressed growth xenograft model, without noticeable visceral detected high-dose group. summary, might new insights designing inhibitors be candidate treatment.

Language: Английский

Comprehensive Analysis of 11 Species of Euodia (Rutaceae) by Untargeted LC-IT-TOF/MS Metabolomics and In Vitro Functional Methods DOI Creative Commons

Xuhong Yong,

Wang Bi, Mengdi Wang

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(5), P. 1059 - 1059

Published: Feb. 28, 2024

The Euodia genus comprises numerous untapped medicinal plants that warrant thorough evaluation for their potential as valuable natural sources of herbal medicine or food flavorings. In this study, untargeted metabolomics and in vitro functional methods were employed to analyze fruit extracts from 11 significant species the genus. An investigation distribution metabolites (quinolone indole quinazoline alkaloids) these indicated E. rutaecarpa (Euodia rutaecarpa) was most widely distributed species, followed by compacta compacta), glabrifolia glabrifolia), austrosinensis austrosinensis), fargesii fargesii). There have been reports on close correlation between alkaloids anti-tumor activity, especially fruits which exhibit effectiveness against various types cancer, such SGC-7901, Hela, A549, other cancer cell lines. Additionally, plant contains alkaloids, possess remarkable antibacterial properties. Our results offer novel insights into utilization resources pharmaceutical industry.

Language: Английский

Citations

4
Tubulin inhibitors. Selected scaffolds and main trends in the design of novel anticancer and antiparasitic agents DOI Creative Commons

M Podolak,

Serhii Holota, Yaroslava Deyak

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 143, P. 107076 - 107076

Published: Dec. 30, 2023

Design of tubulin inhibitors as anticancer drugs dynamically developed over the past 20 years. The modern arsenal potential tubulin-targeting agents is represented by small molecules, monoclonal antibodies, and antibody-drug conjugates. Moreover, targeting has been a successful strategy in development antiparasitic drugs. In present review, an overall picture research using molecules between 2018 2023 provided. data about some most often used prospective chemotypes (privileged heterocycles, moieties natural molecules) synthetic methodologies (analogue-based, fragment-based drug design, molecular hybridization) applied for design novel with impact on system are summarized. prospects multi-target were also highlighted. Reported review contribute to "structure-activity" profile will be useful application medicinal chemists further exploration, improvement, optimization this class molecules.

Language: Английский

Citations

10
Evodiamine: A Extremely Potential Drug Development Candidate of Alkaloids from Evodia rutaecarpa DOI Creative Commons
Longfei Lin, Yuling Liu,

Ruying Tang

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 9843 - 9870

Published: Sept. 1, 2024

Evodiamine (EVO) is a tryptamine indole alkaloid and the main active ingredient in

Language: Английский

Citations

2
Overview of the New Bioactive Heterocycles as Targeting Topoisomerase Inhibitors Useful Against Colon Cancer DOI
Mirelly Barbosa Santos, Misael de Azevedo Teotônio Cavalcanti, Yvnni Maria Sales de Medeiros e Silva

et al.

Anti-Cancer Agents in Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 24(4), P. 236 - 262

Published: Dec. 1, 2023

Colorectal cancer (CRC) is the third most common globally, with high mortality. Metastatic CRC incurable in cases, and multiple drug therapy can increase patients' life expectancy by 2 to 3 years. Efforts are being made understand relationship between topoisomerase enzymes colorectal cancer. Some studies have shown that higher expression of these correlated a poor prognosis for this type One primary drugs used treatment Irinotecan, which be monotherapy or, more commonly, therapeutic schemes such as FOLFIRI (Fluorouracil, Leucovorin, Irinotecan) CAPIRI (Capecitabine Irinotecan). Like Camptothecin, Irinotecan other compounds mechanism action based on formation ternary complex I DNA providing damage it, therefore leading cell death. Thus, review focused principal works published last ten years demonstrate correlation inhibition different isoforms

Language: Английский

Citations

6
Novel sulfonyl-substituted tetrandrine derivatives for colon cancer treatment by inducing mitochondrial apoptosis and inhibiting PI3K/AKT/mTOR pathway DOI
Jie Ling, Xiao Li, Maolin Wang

et al.

Bioorganic Chemistry, Journal Year: 2023, Volume and Issue: 143, P. 107069 - 107069

Published: Dec. 29, 2023

Language: Английский

Citations

5
Design, Synthesis and Biological Evaluation of Plant-Derived Miliusol derivatives achieve TNBC profound regression in vivo DOI

Xi Zhao,

Xiaoling Cheng, Zhiying Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 279, P. 116882 - 116882

Published: Sept. 18, 2024

Language: Английский

Citations

0
Structure-activity relationship study of novel evodiamine amino acid conjugates with potent anti-colorectal cancer efficacy DOI
S. Chen, Xi Zhang,

Hanxuan Mo

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 283, P. 117132 - 117132

Published: Dec. 3, 2024

Language: Английский

Citations

0
Novel Sulfonyl-Substituted Tetrandrine Derivatives for Colon Cancer Treatment by Inducing Mitochondrial Apoptosis and Inhibiting PI3K/AKT/mTOR Pathway DOI
Jie Ling, Xiao Li, Maolin Wang

et al.

Published: Jan. 1, 2023

Tetrandrine (TET) possesses multiple pharmacological activities and could suppress tumor proliferation via PI3K pathway inhibition. However, inferior antitumor activity potential toxicity limit its clinical application. In the present study, a series of 14-sulfonamide sulfonate TET derivatives were designed, synthesized, evaluated for biological activities. Through structural-activity relationship studies, compound 3c with α, β-unsaturated carbonyl group exhibited most potent against all tested cell lines (including Hela, HCT116, HepG2, MCF-7, SHSY5Y), as well negligible normal LO2 HEK293. Additionally, effectively inhibited HCT116 CT26 in vitro increased proportion G2/M phase, activated mitochondrial apoptosis pathway, induced colon cancer by suppressing PI3K/AKT/mTOR pathway. The further molecular docking results confirmed that is potentially bound to residues stronger binding affinity than TET. Ultimately, dramatically suppressed growth xenograft model, without noticeable visceral detected high-dose group. summary, might new insights designing inhibitors be candidate treatment.

Language: Английский

Citations

0