The Journey of DDR1 and DDR2 Kinase Inhibitors as Rising Stars in the Fight Against Cancer

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(12), P. 6535 - 6535

Published: June 18, 2021

Discoidin domain receptor (DDR) is a collagen-activated tyrosine kinase that plays critical roles in regulating essential cellular processes such as morphogenesis, differentiation, proliferation, adhesion, migration, invasion, and matrix remodeling. As result, DDR dysregulation has been attributed to variety of human cancer disorders, for instance, non-small-cell lung carcinoma (NSCLC), ovarian cancer, glioblastoma, breast addition some inflammatory neurodegenerative disorders. Since the target identification early 1990s date, lot efforts have devoted development inhibitors. From medicinal chemistry perspective, we attempted reveal progress most promising DDR1 DDR2 small molecule inhibitors covering their design approaches, structure-activity relationship (SAR), biological activity, selectivity.

Language: Английский

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Synthesis, characterization, molecular docking and in vitro anti-cancer activity studies of new and highly selective 1,2,3-triazole substituted 4-hydroxybenzohyrdazide derivatives

Journal of Molecular Structure, Journal Year: 2023, Volume and Issue: 1283, P. 135247 - 135247

Published: March 2, 2023

Language: Английский

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Anti-Warburg Effect of Melatonin: A Proposed Mechanism to Explain its Inhibition of Multiple Diseases

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(2), P. 764 - 764

Published: Jan. 14, 2021

Glucose is an essential nutrient for every cell but its metabolic fate depends on cellular phenotype. Normally, the product of cytosolic glycolysis, pyruvate, transported into mitochondria and irreversibly converted to acetyl coenzyme A by pyruvate dehydrogenase complex (PDC). In some pathological cells, however, transport blocked due inhibition PDC kinase. This altered metabolism referred as aerobic glycolysis (Warburg effect) common in solid tumors other cells. Switching from mitochondrial oxidative phosphorylation provides diseased cells with advantages because rapid production ATP activation pentose phosphate pathway (PPP) which nucleotides required elevated metabolism. Molecules, called glycolytics, inhibit convert a healthier Glycolytics often function inhibiting hypoxia-inducible factor-1α leading disinhibition allowing intramitochondrial conversion A. Melatonin glycolytic converts Herein we propose that melatonin's explains actions variety diseases. Thus, denominator action switching phenotype

Language: Английский

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Cytotoxic meroterpenoids from brown alga Stypopodium schimperi (Kützing) Verlaque & Boudouresque with comprehensive molecular docking & dynamics and ADME studies

Process Biochemistry, Journal Year: 2023, Volume and Issue: 136, P. 90 - 108

Published: Dec. 2, 2023

Language: Английский

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Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8265 - 8265

Published: May 5, 2023

Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among subtypes of (BC). The advent and application current small-molecule drugs for treating TNBC, well other novel inhibitors, others, have made treatment options TNBC more selective. However, there are still problems, such poor patient tolerance, large administration doses, high dosing frequency, toxic side effects, necessitating development efficient less strategies. High expression Nrf2, vital antioxidant transcription factor, often promotes progression, it is also one most effective targets in BC therapy. We found that MDA-MB-231 cells SUM159 cells, brusatol (BRU) combined polydatin (PD) could significantly inhibit cell proliferation vitro, downregulate Nrf2 protein downstream related target genes Heme Oxygenase-1 (HO-1) NAD(P)H dehydrogenase, quinone 1 (NQO1), promote reactive oxygen species (ROS) levels to further strengthen anti-tumor effect. Furthermore, we discovered our vivo experiments by reducing drug dosage three times, reduce growth while avoiding providing method greater clinical value treatment.

Language: Английский

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Synthesis, Characterization, Molecular Docking and in vitro Biological Studies of Thiazolidin‐4‐one Derivatives as Anti‐Breast‐Cancer Agents

ChemistrySelect, Journal Year: 2023, Volume and Issue: 8(20)

Published: May 24, 2023

Abstract In this study, 16 new compounds were synthesized starting from methylparaben. These consist of eight arylidenehydrazide derivatives and thiazolidin‐4‐on derivatives. All tested against MCF‐7 breast cancer cells MCF10A healthy tissue to determine their anti‐cancer activity. Molecular docking studies also carried out receptor proteins related the growth factor understand inhibition mechanism. According results, 4‐furan‐2‐ylmethoxy)‐N‐(4‐oxo‐2‐phenylthiazolidin‐3‐yl)benzamide ( 5 a ) 4‐(furan‐2‐ylmethoxy)‐N‐(2‐(4‐nitrophenyl)‐4‐oxothiazolidin‐3‐yl)benzamide e found as highest selective most active cells.

Language: Английский

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Cellular and molecular basis of therapeutic approaches to breast cancer

Cellular Signalling, Journal Year: 2022, Volume and Issue: 101, P. 110492 - 110492

Published: Oct. 12, 2022

In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment both primary and metastatic cancers. It's well-known fact that treating cancer is still challenging endeavour even though physicians have fantastic toolset latest options at their disposal. Due to limitations current clinical options, traditional chemotherapeutic drugs, surgical are required address this condition. years, several developments resulting wide range options. This review article discusses cellular molecular foundation endocrine system-based treatments, biological therapies, gene therapy, innovative techniques for cancer.

Language: Английский

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Garcinone E suppresses breast cancer growth and metastasis by modulating tumor‐associated macrophages polarization via STAT6 signaling

Phytotherapy Research, Journal Year: 2023, Volume and Issue: 37(10), P. 4442 - 4456

Published: May 31, 2023

Cancer metastasis remains the most common cause of death in breast cancer patients. Tumor-associated macrophages (TAMs) are a novel therapeutic target for treatment metastatic cancer. Despite good anti-cancer activity garcinone E (GE), there no reports on its effects metastasis. The objective this study was to examine GE RAW 264.7 and THP-1 cells were polarized M2 by IL-4/IL-13 vitro. A 4T1 mouse model tail vein used explore effect growth vivo. In vitro studies showed that dose-dependently suppressed IL-4 + IL-13-induced expression CD206 both differentiated macrophages. However, did not affect LPS IFN-γ-induced polarization M1-like inhibited macrophage specific genes cells, simultaneously impaired macrophage-induced cell proliferation migration, angiogenesis. animal studies, significantly tumor growth, angiogenesis, lung tumor-bearing mice, without causing toxicity. tissues, proportion M2-like TAMs decreased while markedly increased treatment. Mechanistically, phosphorylation STAT6 Our results demonstrate first time suppresses pulmonary modulating through signaling pathway.

Language: Английский

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Local Control of Advanced Breast Cancer—Debate in Multidisciplinary Tumor Board

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 510 - 510

Published: Jan. 15, 2025

Background/Objectives: In Romania, breast cancer is the second most common cancer, third leading cause of death, and prevalent overall. De novo advanced-stage often presents in clinical practice, treatment decisions are best made a multidisciplinary tumor board (MTD) involving surgeons, radiotherapists, medical oncologists. Significant advances systemic therapies, particularly progression-free survival (PFS) overall (OS), have surpassed traditional palliative mastectomy radiotherapy for local control. Therefore, purpose this study to emphasize importance initial choice patient prognosis. Methods: We expose two cases patients with de severe, advanced-stage, hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative their management outcome using cyclin-dependent kinase (CDK) 4/6 inhibitor radiotherapy. An extensive review literature from past five years was also conducted. Results: The role diminishing, as many opting novel including inhibitors, which may improve quality life. Conclusions: First-line therapy locally advanced has suffered changes due implementation targeted therapy. However, drug resistance—either or acquired—remains critical consideration. MTD discussions informed essential achieving personalized, evidence-based outcome.

Language: Английский

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Novel triazoloquinazoline derivatives as VEGFR inhibitors: synthesis, cytotoxic evaluation and in silico studies

Future Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 13

Published: Feb. 25, 2025

New triazoloquinazoline derivatives were synthesized to explore their cytotoxic activity on various cancer cell lines, prompted by the need for effective anticancer agents. All compounds confirmed spectroscopic methods and tested in vitro inhibitory activities against hepatocellular carcinoma (HepG-2), breast (MCF-7), prostate (PC3) lines. Ten VEGFR-2. Additionally, studies investigated most active compound 6, including cycle analysis, apoptotic assessment, effect gene expression, safety profiling, molecular docking, MD simulation, ADMET analysis. Compounds 3a, 3c, 6 exhibited higher MCF-7 than doxorubicin. Compound was potent, arresting at G1 phase showing proapoptotic action. It significantly inhibited VEGFR-2 altered promoting BAX, P21, P53 while downregulating BCL-2. Docking simulations indicated stable interaction with VEGFR-2, safety, profiles suggested favorable drug-likeness safety. has shown promising potential, particularly cancer, but further research is needed confirm these findings address long-term

Language: Английский

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