Investigation into the Neuroprotective and Therapeutic Potential of Plant-Derived Chk2 Inhibitors

被引:0
作者
Kisielewska, Monika [1 ]
Filipski, Michal [1 ]
Sebastianka, Kamil [1 ]
Karas, Dobrawa [1 ]
Molik, Klaudia [1 ]
Choromanska, Anna [2 ]
机构
[1] Wroclaw Med Univ, Fac Med, Mikulicza-Radeckiego 5, PL-50345 Wroclaw, Poland
[2] Wroclaw Med Univ, Fac Pharm, Dept Mol & Cellular Biol, Borowska 211A, PL-50556 Wroclaw, Poland
关键词
plant-derived inhibitors; innovative drugs; cancer treatment; checkpoint kinase 2; DNA repair; apoptosis; cell cycle arrest; checkpoint kinase 2 inhibitors; neurodegenerative diseases; amyotrophic lateral sclerosis; DNA-DAMAGE RESPONSE; KINASE; CHECKPOINT; RHAMNETIN; RESVERATROL; APOPTOSIS; PATHWAY; CELLS; TAU;
D O I
10.3390/ijms25147725
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Nature provides us with a rich source of compounds with a wide range of applications, including the creation of innovative drugs. Despite advancements in chemically synthesized therapeutics, natural compounds are increasingly significant, especially in cancer treatment, a leading cause of death globally. One promising approach involves the use of natural inhibitors of checkpoint kinase 2 (Chk2), a critical regulator of DNA repair, cell cycle arrest, and apoptosis. Chk2's activation in response to DNA damage can lead to apoptosis or DNA repair, influencing glycolysis and mitochondrial function. In cancer therapy, inhibiting Chk2 can disrupt DNA repair and cell cycle progression, promoting cancer cell death and enhancing the efficacy of radiotherapy and chemotherapy. Additionally, Chk2 inhibitors can safeguard non-cancerous cells during these treatments by inhibiting p53-dependent apoptosis. Beyond oncology, Chk2 inhibition shows potential in treating hepatitis C virus (HCV) infections, as the virus relies on Chk2 for RNA replication in neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), in which DNA damage plays a crucial role. Plant-derived Chk2 inhibitors, such as artemetin, rhamnetin, and curcumin, offer a promising future for treating various diseases with potentially milder side effects and broader metabolic impacts compared to conventional therapies. The review aims to underscore the immense potential of natural Chk2 inhibitors in various therapeutic contexts, particularly in oncology and the treatment of other diseases involving DNA damage and repair mechanisms. These natural Chk2 inhibitors hold significant promise for revolutionizing the landscape of cancer treatment and other diseases. Further research into these compounds could lead to the development of innovative therapies that offer hope for the future with fewer side effects and enhanced efficacy.
引用
收藏
页数:13
相关论文
共 50 条
  • [31] Recent Advances in the Isolation Strategies of Plant-Derived Exosomes and Their Therapeutic Applications
    Mun, Jeong-Geon
    Song, Dong-Ha
    Kee, Ji-Ye
    Han, Yohan
    CURRENT ISSUES IN MOLECULAR BIOLOGY, 2025, 47 (03)
  • [32] Targeting Mitochondrial Dysfunction in Neurodegenerative Diseases: Expanding the Therapeutic Approaches by Plant-Derived Natural Products
    Zhang, Xiaoyue
    Wang, Longqin
    Li, Bowen
    Shi, Jiayan
    Xu, Jia
    Yuan, Minlan
    PHARMACEUTICALS, 2023, 16 (02)
  • [33] Part II: New candidates of pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors
    Galal, Shadia A.
    Khairat, Sarah H. M.
    Ali, Hamed I.
    Shouman, Samia A.
    Attia, Yasmin M.
    Ali, Mamdouh M.
    Mahmoud, Abeer E.
    Abdel-Halim, Abeer H.
    Fyiad, Amal A.
    Tab, Ashraf
    El-Shenawy, Reem
    El Abd, Yasmine S.
    Ramdan, Raghda
    El Diwani, Hoda I.
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 144 : 859 - 873
  • [34] Selected Plant-Derived Polyphenols as Potential Therapeutic Agents for Peripheral Artery Disease: Molecular Mechanisms, Efficacy and Safety
    Froldi, Guglielmina
    Ragazzi, Eugenio
    MOLECULES, 2022, 27 (20):
  • [35] Identification of Potent CHK2 Inhibitors-Modulators for Therapeutic Application in Cancer: A Machine Learning Integrated Fragment-Based Drug Design Approach
    Kolpe, Mahima Sudhir
    Suryawanshi, Vikramsinh Sardarsinh
    Eldesoky, Gaber E.
    Hossain, Dilnawaz
    Patil, Pritee Chunarkar
    Bhowmick, Shovonlal
    CHEMISTRYSELECT, 2024, 9 (39):
  • [36] Phosphorylation of p53 on Ser15 during cell cycle caused by Topo I and Topo II inhibitors in relation to ATM and Chk2 activation
    Zhao, Hong
    Traganos, Frank
    Darzynkiewicz, Zbigniew
    CELL CYCLE, 2008, 7 (19) : 3048 - 3055
  • [37] Benzimidazole inhibitors of the protein kinase CHK2: Clarification of the binding mode by flexible side chain docking and protein-ligand crystallography
    Matijssen, Cornelis
    Silva-Santisteban, M. Cris
    Westwood, Isaac M.
    Siddique, Samerene
    Choi, Vanessa
    Sheldrake, Peter
    van Montfort, Rob L. M.
    Blagg, Julian
    BIOORGANIC & MEDICINAL CHEMISTRY, 2012, 20 (22) : 6630 - 6639
  • [38] The cancer therapeutic potential of Chk1 inhibitors: how mechanistic studies impact on clinical trial design
    Thompson, Ruth
    Eastman, Alan
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 2013, 76 (03) : 358 - 369
  • [39] The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression
    Vranceanu, Maria
    Galimberti, Damiano
    Banc, Roxana
    Dragos, Ovidiu
    Cozma-Petrut, Anamaria
    Heghes, Simona-Codruta
    Vostinaru, Oliviu
    Cuciureanu, Magdalena
    Stroia, Carmina Mariana
    Miere, Doina
    Filip, Lorena
    PLANTS-BASEL, 2022, 11 (19):
  • [40] Plant-derived nanovesicles: Further exploration of biomedical function and application potential
    Li, Aixue
    Li, Dan
    Gu, Yongwei
    Liu, Rongmei
    Tang, Xiaomeng
    Zhao, Yunan
    Qi, Fu
    Wei, Jifu
    Liu, Jiyong
    ACTA PHARMACEUTICA SINICA B, 2023, 13 (08) : 3300 - 3320