Molecular Modelling Lab (MML), Department of Pharmaceutical Sciences and Drug research, Punjabi University, Patiala, Punjab, 147002, India.
Indian Council of Medical Research, New Delhi, India.
Eur J Med Chem. 2018 May 10;151:62-97. doi: 10.1016/j.ejmech.2018.03.057. Epub 2018 Mar 24.
Complex diseases comprises of highly complicated etiology resulting in limited applicability of conventional targeted therapies. Consequently, conventional medicinal compounds suffer major failure when used for such disease conditions. Additionally, development of multidrug resistance (MDR), adverse drug reactions and clinical specificity of single targeted drug therapy has increased thrust for novel drug therapy. In this rapidly evolving era, natural product-based discovery of hybrid molecules or multi-targeted drug therapies have shown promising results and are trending now a days. Historically, nature has blessed human with different sources viz. plant, animal, microbial, marine and ethnopharmaceutical sources which has given a wide variety of medicinally active compounds. These compounds from natural origin are always choice of interest of medicinal chemists because of their minimum side effects. Hybrid molecules synthesized by fusing or conjugating different active molecules obtained from these sources are reported to synergistically block different pathways which contribute in the pathogenesis of complex diseases. This review strives to encompass all natural product-derived hybrid molecules which act as multi-targeting agents striking various targets involved in different pathways of complex diseased conditions reported in literature.
复杂疾病的病因非常复杂,导致传统的靶向治疗方法适用性有限。因此,传统的药用化合物在用于此类疾病时往往会失败。此外,多药耐药性(MDR)的发展、药物不良反应以及单一靶向药物治疗的临床特异性,都增加了对新型药物治疗的需求。在这个快速发展的时代,基于天然产物的杂交分子或多靶点药物治疗的发现已经显示出了有前途的结果,并且现在已经成为一种趋势。从历史上看,大自然赋予了人类不同的资源,如植物、动物、微生物、海洋和民族药物资源,这些资源提供了各种各样的具有药用活性的化合物。这些来自天然来源的化合物一直是药物化学家感兴趣的选择,因为它们的副作用最小。通过融合或连接从这些来源获得的不同活性分子合成的杂交分子被报道具有协同作用,可以阻断导致复杂疾病发病机制的不同途径。本综述旨在涵盖所有作为多靶点药物的天然产物衍生的杂交分子,这些药物针对文献中报道的复杂疾病状态的不同途径中涉及的各种靶点。