Kerru Nagaraju, Singh Parvesh, Koorbanally Neil, Raj Raghu, Kumar Vipan
School of Chemistry and Physics, University of KwaZulu Natal, P/Bag X54001, Westville, Durban 4000, South Africa.
School of Chemistry and Physics, University of KwaZulu Natal, P/Bag X54001, Westville, Durban 4000, South Africa.
Eur J Med Chem. 2017 Dec 15;142:179-212. doi: 10.1016/j.ejmech.2017.07.033. Epub 2017 Jul 20.
In spite of the development of a large number of novel anticancer drugs over the years, Cancer remains as a prominent cause of death, worldwide. Numerous drugs that are currently in clinical practice have developed multidrug resistance along with fatal side effects. Therefore, the utilization of single-target therapy is incapable of providing an effective control on the malignant process. Molecular hybridization, involving a combination of two or more pharmacophores of bioactive scaffolds to generate a single molecular architecture with improved affinity and activity, in comparison to their parent molecules, has emerged as a promising strategy in recent drug discovery research. Hybrid anticancer drugs are of great therapeutic interests since they can potentially overcome most of the pharmacokinetic drawbacks encountered with conventional anticancer drugs. Strategically, the design of anticancer drugs involved the blending or linking of an anticancer drug with another anticancer drug or a carrier molecule which can efficiently target cancer cells with improved biological potential. Major advantages of hybrid anticancer drugs involved increased specificity, better patient compliance, and lower side effects along with reduction in chemo-resistance. The successful utilization of this technique in design and synthesis of novel anticancer hybrids has been well illustrated and documented in the literature. The purpose of the present review article will be to provide an emphasis on the recent developments (2015-16) in anticancer hybrids with insights into their structure-activity relationship (SAR) and mechanism of action.
尽管多年来开发了大量新型抗癌药物,但癌症仍是全球主要的死亡原因。目前临床实践中使用的许多药物都产生了多药耐药性以及致命的副作用。因此,单靶点治疗无法有效控制恶性肿瘤进程。分子杂交是将两种或更多生物活性支架的药效基团组合,以生成一种与母体分子相比具有更高亲和力和活性的单一分子结构,在最近的药物发现研究中已成为一种有前景的策略。杂交抗癌药物具有很大的治疗价值,因为它们有可能克服传统抗癌药物遇到的大多数药代动力学缺点。从策略上讲,抗癌药物的设计涉及将一种抗癌药物与另一种抗癌药物或载体分子混合或连接,这种载体分子可以有效地靶向癌细胞并具有更高的生物学活性。杂交抗癌药物的主要优点包括特异性增加、患者依从性更好、副作用更低以及化疗耐药性降低。该技术在新型抗癌杂交药物设计和合成中的成功应用已在文献中得到充分说明和记载。本综述文章的目的是重点介绍抗癌杂交药物的最新进展(2015 - 2016年),深入探讨其构效关系(SAR)和作用机制。