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

и другие.

Опубликована: Янв. 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.

Язык: 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

и другие.

Molecules, Год журнала: 2024, Номер 29(5), С. 1059 - 1059

Опубликована: Фев. 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.

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2023, Номер 143, С. 107076 - 107076

Опубликована: Дек. 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.

Язык: Английский

Процитировано

10

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

Ruying Tang

и другие.

International Journal of Nanomedicine, Год журнала: 2024, Номер Volume 19, С. 9843 - 9870

Опубликована: Сен. 1, 2024

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

Язык: Английский

Процитировано

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

и другие.

Anti-Cancer Agents in Medicinal Chemistry, Год журнала: 2023, Номер 24(4), С. 236 - 262

Опубликована: Дек. 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

Язык: Английский

Процитировано

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

и другие.

Bioorganic Chemistry, Год журнала: 2023, Номер 143, С. 107069 - 107069

Опубликована: Дек. 29, 2023

Язык: Английский

Процитировано

5

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

Xi Zhao,

Xiaoling Cheng, Zhiying Liu

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 279, С. 116882 - 116882

Опубликована: Сен. 18, 2024

Язык: Английский

Процитировано

0

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

Hanxuan Mo

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2024, Номер 283, С. 117132 - 117132

Опубликована: Дек. 3, 2024

Язык: Английский

Процитировано

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

и другие.

Опубликована: Янв. 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.

Язык: Английский

Процитировано

0