Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids

被引:402
作者
Nepali, Kunal [1 ]
Sharma, Sahil [1 ]
Sharma, Manmohan [1 ]
Bedi, P. M. S. [1 ]
Dhar, K. L. [2 ]
机构
[1] Guru Nanak Dev Univ, Dept Pharmaceut Sci, Amritsar 143005, Punjab, India
[2] ISF Coll Pharm, Moga, Punjab, India
关键词
Molecular hybridization; Fusion; Cancer; Cytotoxic; Tubulin; Colchicine; ESTROGEN-RECEPTOR MODULATORS; DNA CROSS-LINKING; QUINOXALINE-CARBOHYDRATE HYBRIDS; DIVERSITY-ORIENTED SYNTHESIS; TOPOISOMERASE-I INHIBITORS; APOPTOSIS INDUCING ABILITY; OXIDE-DONATING ASPIRIN; ANTI-NEOPLASTIC AGENTS; VIRUS NS5B POLYMERASE; HUMAN CANCER-CELLS;
D O I
10.1016/j.ejmech.2014.03.018
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bin target as one single molecule or to counterbalance the known side effects associated with the other hybrid part. The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids. (C) 2014 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:422 / 487
页数:66
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