Novel Combretastatin A-4 Analogs-Design, Synthesis, and Antiproliferative and Anti-Tubulin Activity

被引:1
|
作者
Jedrzejczyk, Marta [1 ]
Morabito, Benedetta [2 ]
Zyzynska-Granica, Barbara [3 ]
Struga, Marta [3 ]
Janczak, Jan [4 ]
Aminpour, Maral [5 ]
Tuszynski, Jack A. [2 ,6 ,7 ]
Huczynski, Adam [1 ]
机构
[1] Adam Mickiewicz Univ, Fac Chem, Dept Med Chem, Uniwersytetu Poznanskiego 8, PL-61614 Poznan, Poland
[2] Dept Mech & Aerosp Engn, Politecn Torino, I-10129 Turin, Italy
[3] Med Univ Warsaw, Chair & Dept Biochem, Banacha 1, PL-02097 Warsaw, Poland
[4] Polish Acad Sci, Inst Low Temp & Struct Res, Okolna 2, PL-50323 Wroclaw, Poland
[5] Univ Alberta, Dept Biomed Engn, Edmonton, AB T6G 1H9, Canada
[6] Silesian Tech Univ, Dept Data Sci & Engn, PL-44100 Gliwice, Poland
[7] Univ Alberta, Dept Phys, Edmonton, AB T6G 2E1, Canada
来源
MOLECULES | 2024年 / 29卷 / 10期
关键词
antiproliferative activity; binding energy; colchicine binding site; combretastatin; tubulin-targeting agent; INTERMOLECULAR INTERACTIONS; TUBULIN; INHIBITORS; BINDING; AGENTS; TOOLS; ASSAY;
D O I
10.3390/molecules29102200
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
Combretastatins isolated from the Combretum caffrum tree belong to a group of closely related stilbenes. They are colchicine binding site inhibitors which disrupt the polymerization process of microtubules in tubulins, causing mitotic arrest. In vitro and in vivo studies have proven that some combretastatins exhibit antitumor properties, and among them, combretastatin A-4 is the most active mitotic inhibitor. In this study, a series of novel combretastatin A-4 analogs containing carboxylic acid, ester, and amide moieties were synthesized and their cytotoxic activity against six tumor cell lines was determined using sulforhodamine B assay. For the most cytotoxic compounds (8 and 20), further studies were performed. These compounds were shown to induce G0/G1 cell cycle arrest in MDA and A549 cells, in a concentration-dependent manner. Moreover, in vitro tubulin polymerization assays showed that both compounds are tubulin polymerization enhancers. Additionally, computational analysis of the binding modes and binding energies of the compounds with respect to the key human tubulin isotypes was performed. We have obtained a satisfactory correlation of the binding energies with the IC50 values when weighted averages of the binding energies accounting for the abundance of tubulin isotypes in specific cancer cell lines were computed.
引用
收藏
页数:22
相关论文
共 50 条
  • [21] Design and Synthesis of Tubulin and Histone Deacetylase Inhibitor Based on iso-Combretastatin A-4
    Lamaa, Diana
    Lin, Hsin-Ping
    Zig, Lena
    Bauvais, Cyril
    Bollot, Guillaume
    Bignon, Jerome
    Levaique, Helene
    Pamlard, Olivier
    Dubois, Joelle
    Ouaissi, Mehdi
    Souce, Martin
    Kasselouri, Athena
    Saller, Francois
    Borgel, Delphine
    Jayat-Vignoles, Chantal
    Al-Mouhammad, Hazar
    Feuillard, Jean
    Benihoud, Karim
    Alami, Mouad
    Hamze, Abdallah
    JOURNAL OF MEDICINAL CHEMISTRY, 2018, 61 (15) : 6574 - 6591
  • [22] Design, concise synthesis and evaluation of novel amide-based combretastatin A-4 analogues as potent tubulin inhibitors
    Ma, Yufeng
    Wang, Ting
    Cheng, Li
    Ma, Xuanxuan
    Li, Rou
    Zhang, Mengting
    Chen, Jingkao
    Zhao, Peiliang
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2024, 108
  • [23] Design, Synthesis and Biological Evaluation of Novel Aminosaccharide Derivatives of Combretastatin A-4
    Tang, Yan
    Tu, Zhewei
    Sun, Jing
    Zhu, Xiong
    Liu, Kun
    He, Shuying
    Xu, Yungen
    LETTERS IN DRUG DESIGN & DISCOVERY, 2013, 10 (10) : 935 - 941
  • [24] Combretastatin A-4 disodium phosphate: A novel tubulin binding agent with potent activity in murine tumours
    Horsman, M
    Murata, R
    Ehrnrooth, E
    Ladekarl, M
    Breidahl, T
    Nielsen, F
    Maxwell, R
    Stokilde-Jorgensen, H
    Overgaard, J
    ANNALS OF ONCOLOGY, 1998, 9 : 91 - 91
  • [25] Lead identification of conformationally restricted benzoxepin type combretastatin analogs: synthesis, antiproliferative activity, and tubulin effects
    Barrett, Irene
    Carr, Miriam
    O'Boyle, Niamh
    Greene, Lisa M.
    Knox, Andrew J. S.
    Lloyd, David G.
    Zisterer, Daniela M.
    Meegan, Mary J.
    JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2010, 25 (02) : 180 - 194
  • [26] Synthesis and Evaluation of Azetidinone Analogues of Combretastatin A-4 as Tubulin Targeting Agents
    O'Boyle, Niamh M.
    Carr, Miriam
    Greene, Lisa M.
    Bergin, Orla
    Nathwani, Seema M.
    McCabe, Thomas
    Lloyd, David G.
    Zisterer, Daniela M.
    Meegan, Mary J.
    JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (24) : 8569 - 8584
  • [27] Design and Synthesis of New Tubulin Polymerization Inhibitors Inspired from Combretastatin A-4: An Anticancer Agent
    Sharma, Akanksha
    Talimarada, Doddabasappa
    Yadav, Umesh Prasad
    Singh, Nidhi
    Reddy, A. Sudharshan
    Bag, Debojyoti
    Biswas, Krishna
    Baidya, Amit
    Borale, Asha N.
    Shinde, Dhananjay
    Singh, Sandeep
    Holla, Harish
    CHEMISTRYSELECT, 2020, 5 (37): : 11560 - 11572
  • [28] Recent Trends in Tubulin-Binding Combretastatin A-4 Analogs for Anticancer Drug Development
    Paidakula, Suresh
    Nerella, Srinivas
    Kankala, Shravankumar
    Kankala, Ranjith Kumar
    CURRENT MEDICINAL CHEMISTRY, 2022, 29 (21) : 3748 - 3773
  • [29] Synthesis of New Combretastatin A-4 Analogues and Study of Their Anti-Inflammatory Activity
    Davydova, M. P.
    Sorokina, I. V.
    Tolstikova, T. G.
    Mamatyuk, V. I.
    Fadeev, D. S.
    Vasilevsky, S. F.
    RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY, 2015, 41 (01) : 70 - 76
  • [30] Synthesis of new combretastatin A-4 analogues and study of their anti-inflammatory activity
    M. P. Davydova
    I. V. Sorokina
    T. G. Tolstikova
    V. I. Mamatyuk
    D. S. Fadeev
    S. F. Vasilevsky
    Russian Journal of Bioorganic Chemistry, 2015, 41 : 70 - 76