Have molecular hybrids delivered effective anti-cancer treatments and what should future drug discovery focus on?

被引:32
作者
Shalini [1 ]
Kumar, Vipan [1 ]
机构
[1] Guru Nanak Dev Univ, Dept Chem, Amritsar, Punjab, India
关键词
Cancer; hybrid molecules; drug design; structure-activity relationship; clinical trials; approved drugs; HISTONE DEACETYLASE INHIBITORS; CELL-CYCLE ARREST; BIOLOGICAL EVALUATION; HYDROXAMIC ACIDS; BREFELDIN-A; ANTIPROLIFERATIVE EVALUATION; DERIVATIVES SYNTHESIS; ANTITUMOR-ACTIVITY; NITROGEN MUSTARDS; TOPOISOMERASE-II;
D O I
10.1080/17460441.2021.1850686
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction Cancer continues to be a big threat and its treatment is a huge challenge among the medical fraternity. Conventional anti-cancer agents are losing their efficiency which highlights the need to introduce new anti-cancer entities for treating this complex disease. A hybrid molecule has a tendency to act through varied modes of action on multiple targets at a given time. Thus, there is the significant scope with hybrid compounds to tackle the existing limitations of cancer chemotherapy. Area Covered This perspective describes the most significant hybrids that spring hope in the field of cancer chemotherapy. Several hybrids with anti-proliferative/anti-tumor properties currently approved or in clinical development are outlined, along with a description of their mechanism of action and identified drug targets. Expert opinion The success of molecular hybridization in cancer chemotherapy is quite evident by the number of molecules entering into clinical trials and/or have entered the drug market over the past decade. Indeed, the recent advancements and co-ordinations in the interface between chemistry, biology, and pharmacology will help further the advancement of hybrid chemotherapeutics in the future.
引用
收藏
页码:335 / 363
页数:29
相关论文
共 152 条
[11]  
Boloor A, 2012, CHEM COMPOUNDS
[12]   Novel hybrids from N-hydroxyarylamide and indole ring through click chemistry as histone deacetylase inhibitors with potent antitumor activities [J].
Cai, Mao ;
Hu, Jie ;
Tian, Ji-Lai ;
Yan, Huang ;
Zheng, Chen-Guo ;
Hu, Wan-Le .
CHINESE CHEMICAL LETTERS, 2015, 26 (06) :675-680
[13]   Lenvatinib, a molecule with versatile application: from preclinical evidence to future development in anti-cancer treatment [J].
Capozzi, Monica ;
De Divitiis, Chiara ;
Ottaiano, Alessandro ;
von Arx, Claudia ;
Scala, Stefania ;
Tatangelo, Fabiana ;
Delrio, Paolo ;
Tafuto, Salvatore .
CANCER MANAGEMENT AND RESEARCH, 2019, 11 :3847-3860
[14]   Synthesis and evaluation of cytotoxic activities of new guanidines derived from carbazoles [J].
Caruso, Anna ;
Sinicropi, Maria Stefania ;
Lancelot, Jean-Charles ;
El-Kashef, Hussein ;
Saturnino, Carmela ;
Aubert, Genevieve ;
Ballandonne, Celine ;
Lesnard, Aurelien ;
Cresteil, Thierry ;
Dallemagne, Patrick ;
Rault, Sylvain .
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (02) :467-472
[15]   Blockade of oncogenic IκB kinase activity in diffuse large B-cell lymphoma by bromodomain and extraterminal domain protein inhibitors [J].
Ceribelli, Michele ;
Kelly, Priscilla N. ;
Shaffer, Arthur L. ;
Wright, George W. ;
Xiao, Wenming ;
Yang, Yibin ;
Griner, Lesley A. Mathews ;
Guha, Rajarshi ;
Shinn, Paul ;
Keller, Jonathan M. ;
Liu, Dongbo ;
Patel, Paresma R. ;
Ferrer, Marc ;
Joshi, Shivangi ;
Nerle, Sujata ;
Sandy, Peter ;
Normant, Emmanuel ;
Thomas, Craig J. ;
Staudt, Louis M. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (31) :11365-11370
[16]   A carbazole derivative synthesis for stabilizing the quadruplex structure [J].
Chang, CC ;
Wu, JY ;
Chang, TC .
JOURNAL OF THE CHINESE CHEMICAL SOCIETY, 2003, 50 (02) :185-188
[17]   Synthesis and structure-activity relationship of histone deacetylase (HDAC) inhibitors with triazole-linked cap group [J].
Chen, Po C. ;
Patil, Vishal ;
Guerrant, William ;
Green, Patience ;
Oyelere, Adegboyega K. .
BIOORGANIC & MEDICINAL CHEMISTRY, 2008, 16 (09) :4839-4853
[18]   Therapeutic Potential of Nitrogen Mustard Based Hybrid Molecules [J].
Chen, Yiming ;
Jia, Yuping ;
Song, Weiguo ;
Zhang, Lei .
FRONTIERS IN PHARMACOLOGY, 2018, 9
[19]   YM155 as an inhibitor of cancer stemness simultaneously inhibits autophosphorylation of epidermal growth factor receptor and G9a-mediated stemness in lung cancer cells [J].
Cheng, Chun-Chia ;
Chang, Jungshan ;
Huang, Stanley Ching-Cheng ;
Lin, Huan-Chau ;
Ho, Ai-Sheng ;
Lim, Ken-Hong ;
Chang, Chun-Chao ;
Huang, Ling ;
Chang, Yu-Cheng ;
Chang, Yi-Fang ;
Wu, Cheng-Wen .
PLOS ONE, 2017, 12 (08)
[20]   Design, synthesis and biological evaluation of 6-(nitroimidazole-1H-alkyloxyl)-4-anilinoquinazolines as efficient EGFR inhibitors exerting cytotoxic effects both under normoxia and hypoxia [J].
Cheng, Weiyan ;
Zhu, Shijun ;
Ma, Xiaodong ;
Qiu, Ni ;
Peng, Peng ;
Sheng, Rong ;
Hu, Yongzhou .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 89 :826-834