Singh Swati, Awasthi Manika, Pandey Veda P, Dwivedi Upendra N
Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, Department of Biochemistry, University of Lucknow, Lucknow-226007. India.
Curr Protein Pept Sci. 2018;19(3):238-274. doi: 10.2174/1389203718666170106102223.
Cancer, characterized by uncontrolled growth and proliferation of cells, is affecting millions of people every year and estimated as the second leading cause of death. Its successful treatment yet remains a challenge due to the lack of selectivity, toxicity and the development of multidrug resistant cells to the currently available drugs. Plant derived natural products hold great promise for discovery and development of new pharmaceuticals against cancer as evident by the fact that out of 121 drugs prescribed for cancer treatment till date, 90 are derived from plant sources. Furthermore, the plant derived therapeutic molecules are also considered as safer substitutes to those of synthetic ones. In this review, the therapeutic potentials of plant derived natural products belonging to secondary metabolites, namely alkaloids, flavonoids and terpenoids as anticancer molecules, involving various strategies of treatment, have been discussed with special reference to topoisomerases (Topo), cyclooxygenases (COX), lipoxygenase (LOX) and aromatase as enzymatic targets for various types of cancers. Furthermore, in view of the recent advances made in the field of computer aided drug design, the present review also discusses the use of computational approaches such as ADMET, molecular docking, molecular dynamics simulation and QSAR to assess and predict the safety, efficacy, potency and identification of such potent anticancerous therapeutic molecules.
癌症的特征是细胞不受控制地生长和增殖,每年影响着数百万人,据估计是第二大死因。由于缺乏选择性、毒性以及对现有药物产生多药耐药性细胞的出现,其成功治疗仍然是一项挑战。植物衍生的天然产物在发现和开发抗癌新药方面具有巨大潜力,从迄今用于癌症治疗的121种药物中,有90种来自植物来源这一事实可见一斑。此外,植物衍生的治疗分子也被认为是合成分子的更安全替代品。在本综述中,已讨论了属于次生代谢物的植物衍生天然产物,即生物碱、黄酮类化合物和萜类化合物作为抗癌分子的治疗潜力,涉及各种治疗策略,并特别提及拓扑异构酶(Topo)、环氧化酶(COX)、脂氧合酶(LOX)和芳香化酶作为各类癌症的酶靶点。此外,鉴于计算机辅助药物设计领域的最新进展,本综述还讨论了使用诸如ADMET、分子对接、分子动力学模拟和QSAR等计算方法来评估和预测此类强效抗癌治疗分子的安全性、有效性、效力以及进行鉴定。