Drug tolerant persister cell plasticity in cancer: A revolutionary strategy for more effective anticancer therapies

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 14, 2024

Non-genetic mechanisms have recently emerged as important drivers of anticancer drug resistance. Among these, the tolerant persister (DTP) cell phenotype is attracting more and attention giving a predominant non-genetic role in cancer therapy The DTP characterized by quiescent or slow-cell-cycle reversible state subpopulation inert specialization to stimuli, which tolerates exposure some extent through interaction multiple underlying recovering growth proliferation after withdrawal, ultimately leading treatment resistance recurrence. Therefore, targeting cells anticipated provide new opportunities for patients, although our current knowledge these remains limited. In this review, we comprehensive overview formation characteristics cells, investigate potential drugs (including preclinical drugs, novel use old natural products) based on different medicine models, discuss necessity feasibility anti-DTP therapy, related application forms, future issues that will need be addressed advance emerging field towards clinical applications. Nonetheless, understanding functions may enable us develop effective improve outcomes patients.

Language: Английский

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Modulation of TLR/NF-κB/NLRP Signaling by Bioactive Phytocompounds: A Promising Strategy to Augment Cancer Chemotherapy and Immunotherapy

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: March 1, 2022

Tumors often progress to a more aggressive phenotype resist drugs. Multiple dysregulated pathways are behind this tumor behavior which is known as cancer chemoresistance. Thus, there an emerging need discover pivotal signaling involved in the resistance chemotherapeutic agents and immunotherapy. Reports indicate critical role of toll-like receptor (TLR)/nuclear factor-κB (NF-κB)/Nod-like pyrin domain-containing (NLRP) pathway initiation, progression, development. Therefore, targeting TLR/NF-κB/NLRP promising strategy augment chemotherapy immunotherapy combat Considering potential phytochemicals regulation multiple during promotion, such compounds could be suitable candidates against chemoresistance.This first comprehensive systematic review regarding mitigation chemoresistance by regulating immunotherapy.A was designed based on Web Science, PubMed, Scopus, Cochrane electronic databases. The Preferred Reporting Items for Systematic Reviews Meta-Analyses guidelines were followed include papers chemotherapy/immunotherapy/chemoresistance phytochemicals.Phytochemicals multi-targeting interconnected mediators. Employing phenolic compounds, alkaloids, terpenoids, sulfur managing through modulation pathway. Novel delivery systems chemotherapy/immunotherapy also highlighted.Targeting with bioactive phytocompounds reverses improves outcome both preclinical clinical stages.

Language: Английский

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Natural product evodiamine-inspired medicinal chemistry: Anticancer activity, structural optimization and structure-activity relationship

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 247, P. 115031 - 115031

Published: Dec. 17, 2022

Language: Английский

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PROTAC derivatization of natural products for target identification and drug discovery: Design of evodiamine-based PROTACs as novel REXO4 degraders

Journal of Advanced Research, Journal Year: 2023, Volume and Issue: 63, P. 219 - 230

Published: Nov. 1, 2023

Natural products (NPs) play a crucial role in the development of therapeutic drugs. However, it is still highly challenging to identify targets NPs. Besides, NPs usually exert their pharmacological activities via acting on multiple or pathways, which also poses great difficulties for target identification

Language: Английский

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Evodiamine: A Privileged Structure with Broad-ranging Biological Activities

Mini-Reviews in Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 22(21), P. 2680 - 2701

Published: April 5, 2022

Evodiamine (EVO) is a natural quinolone alkaloid firstly isolated from the fruit of Evodia rutaecarpa, which one most frequently used traditional Chinese herb for treating variety ailments, including headaches, abdominal pain, vomiting, diarrhea, amenorrhea difficult menstruation, postpartum hemorrhage, and other diseases. Latest pharmacological studies showed that EVO possesses broad spectrum activities through different mechanisms. However, its moderate poor physicochemical properties have hampered clinical application. In this regard, modification aiming at seeking derivatives with more potency better has been extensively emerging. These exhibit diverse biological activities, antitumor, anti-Alzheimer's disease, anti-pulmonary hypertension, anti-fungi, thermogenic via Moreover, they are described to act as single, dual, or multiple inhibitors agonists many proteins, such topoisomerase I, II, tubulin, histone deacetylase, sirtuins, butyrylcholinesterase, phosphodiesterase 5, transient receptor potential vanilloid 1. hitherto, there no comprehensive review systematically summarize EVO. Considering perspective, paper aims provide description them by focusing on their activities. For each activity, mechanisms main structureactivity relationships (SARs) will be presented in cases where adequate information available. Finally, future directions class compounds discussed. This helpful understanding encouraging further exploration

Language: Английский

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Development of a new drug candidate for the inhibition of Lassa virus glycoprotein and nucleoprotein by modification of evodiamine as promising therapeutic agents

Frontiers in Microbiology, Journal Year: 2023, Volume and Issue: 14

Published: July 11, 2023

The Lassa virus (LASV), an RNA prevalent in West and Central Africa, causes severe hemorrhagic fever with a high fatality rate. However, no FDA-approved treatments or vaccines exist. Two crucial proteins, LASV glycoprotein nucleoprotein, play vital roles pathogenesis are potential therapeutic targets. As effective for many emerging infections remain elusive, cutting-edge drug development approaches essential, such as identifying molecular targets, screening lead molecules, repurposing existing drugs. Bioinformatics computational biology expedite discovery pipelines, using data science to identify predict structures, model interactions. These techniques also facilitate leads optimal drug-like properties, reducing time, cost, complexities associated traditional development. Researchers have employed advanced design methods docking, pharmacokinetics, drug-likeness, dynamics simulation investigate evodiamine derivatives inhibitors. results revealed remarkable binding affinities, outperforming standard compounds. Additionally, active suggest stability when bound target receptors. promising findings indicate that may offer superior pharmacokinetics drug-likeness serving valuable resource professionals developing synthetic drugs combat the virus.

Language: Английский

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Discovery of Novel Polycyclic Heterocyclic Derivatives from Evodiamine for the Potential Treatment of Triple-Negative Breast Cancer

Journal of Medicinal Chemistry, Journal Year: 2021, Volume and Issue: 64(23), P. 17346 - 17365

Published: Nov. 30, 2021

Evodiamine (Evo) is a quinazolinocarboline alkaloid found in Evodia rutaecarpa and exhibits moderate antiproliferative activity. Herein, we report using scaffold-hopping approach to identify series of novel polycyclic heterocyclic derivatives based on Evo as the topoisomerase I (Top1) inhibitor for treatment triple-negative breast cancer (TNBC), which an aggressive subtype with limited options. The most potent compound 7f inhibited cell growth human carcinoma line (MDA-MB-231) IC50 value 0.36 μM. Further studies revealed that Top1 was target 7f, directly induced irreversible Top1–DNA covalent complex formation or oxidative DNA lesion through indirect mechanism mediated by reactive oxygen species. More importantly, vivo showed exhibited antitumor activity TNBC-patient-derived tumor xenograft model. These results suggest deserves further investigation promising candidate TNBC.

Language: Английский

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Design, Synthesis, and Biological Evaluation of Novel Evodiamine Derivatives as Potential Antihepatocellular Carcinoma Agents

Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 65(11), P. 7975 - 7992

Published: May 31, 2022

Evodiamine has many biological activities. Herein, we synthesize 23 disubstituted derivatives of N14-phenyl or the E-ring evodiamine and conduct systematic structure–activity relationship studies. In vitro antiproliferative activity indicated that compounds F-3 F-4 dramatically inhibited proliferation Huh7 (IC50 = 0.05 0.04 μM, respectively) SK-Hep-1 0.07 0.06 cells. Furthermore, could double inhibit topoisomerases I II, invasion migration, block cell cycle to G2/M stage, induce apoptosis as well. Additionally, also activation HSC-T6 reduce secretion collagen type slow down progression liver fibrosis. Most importantly, compound (TGI 60.36%) tumor growth more significantly than positive drug sorafenib. To sum up, excellent potential a strong candidate for therapy hepatocellular carcinoma.

Language: Английский

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Design, synthesis and bioactivity evaluation of favorable evodiamine derivative scaffold for developing cancer therapy

European Journal of Medicinal Chemistry, Journal Year: 2022, Volume and Issue: 239, P. 114530 - 114530

Published: June 15, 2022

Language: Английский

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Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: June 17, 2022

Background: The patent literature contains a large amount of information on the internal state current industrial technologies that are not available in other studies. Scientific articles direct achievements theoretical research this field and can reveal how theories basic have developed. In study, progress status natural anticancer products were summarized, hotspots explored through analysis relevant scientific articles. Methods: Patent data retrieved from incoPat retrieval database, paper Web Science core set PubMed. GraphPad Prism 8, Microsoft Excel 2010, CiteSpace 5.8.R3 used to perform visual processing. analyzed includes applicant type, country (or region), technical subject. article academic groups, subject areas, keyword clustering, burst detection. Results: A total 20,435 families 38,746 collected by 4 January 2022. At present, antitumor drugs derived mainly include 1) apoptosis inducers such as curcumin, gallic acid, resveratrol, Theranekron D6, gaillardin; 2) topoisomerase inhibitors camptothecins, scaffold-hopped flavones, podophyllotoxin, oxocrebanine, evodiamine derivatives; 3) telomerase camptothecin isoquinoline alkaloids Chelidonium majus , amentoflavone, emodin; 4) microtubule kolaflavanone, tanshinone IIA analog, eugenol, millepachine; 5) immunomodulators fucoidan, myricetin, bergapten, atractylenolide I; 6) tumor microenvironment regulators beta-escin icaritin; 7) multidrug resistance reversal agents berberine, quercetin, dihydromyricetin; 8) antiangiogenic antimetastatic epigallocatechin-3-gallate, lupeol, ononin, saikosaponin A. Conclusion: Anticancer product technology was introduced earlier, but later development momentum insufficient. addition, activities relatively closed, exchanges need be strengthened. Currently, medicinal plants mechanism active still hotspots, especially those related immune checkpoints, essential oils, metastatic cancer. Theories traditional Chinese medicine (TCM), “restraining excessiveness acquire harmony,” “same treatment for different diseases,” “Meridian induction theory,” “Fuzheng Quxie,” important guiding significance mechanisms new provide ideas process. Systematic Review Registration : [ https://sourceforge.net/projects/citespace/ ], identifier [000755430500001].

Language: Английский

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