Singh Ankit Kumar, Kumar Adarsh, Singh Harshwardhan, Sonawane Pankaj, Paliwal Harshali, Thareja Suresh, Pathak Prateek, Grishina Maria, Jaremko Mariusz, Emwas Abdul-Hamid, Yadav Jagat Pal, Verma Amita, Khalilullah Habibullah, Kumar Pradeep
Department of Pharmaceutical Sciences and Natural Products, Central University of Punjab, Ghudda, Bathinda 154001, India.
Laboratory of Computational Modeling of Drugs, Higher Medical and Biological School, South Ural State University, 454008 Chelyabinsk, Russia.
Pharmaceuticals (Basel). 2022 Aug 28;15(9):1071. doi: 10.3390/ph15091071.
Cancer is a complex disease, and its treatment is a big challenge, with variable efficacy of conventional anticancer drugs. A two-drug cocktail hybrid approach is a potential strategy in recent drug discovery that involves the combination of two drug pharmacophores into a single molecule. The hybrid molecule acts through distinct modes of action on several targets at a given time with more efficacy and less susceptibility to resistance. Thus, there is a huge scope for using hybrid compounds to tackle the present difficulties in cancer medicine. Recent work has applied this technique to uncover some interesting molecules with substantial anticancer properties. In this study, we report data on numerous promising hybrid anti-proliferative/anti-tumor agents developed over the previous 10 years (2011-2021). It includes quinazoline, indole, carbazole, pyrimidine, quinoline, quinone, imidazole, selenium, platinum, hydroxamic acid, ferrocene, curcumin, triazole, benzimidazole, isatin, pyrrolo benzodiazepine (PBD), chalcone, coumarin, nitrogen mustard, pyrazole, and pyridine-based anticancer hybrids produced via molecular hybridization techniques. Overall, this review offers a clear indication of the potential benefits of merging pharmacophoric subunits from multiple different known chemical prototypes to produce more potent and precise hybrid compounds. This provides valuable knowledge for researchers working on complex diseases such as cancer.
癌症是一种复杂的疾病,其治疗是一项巨大的挑战,传统抗癌药物的疗效各不相同。双药鸡尾酒混合方法是近年来药物发现中的一种潜在策略,它涉及将两种药物药效基团组合成一个单一分子。该混合分子在给定时间通过不同的作用模式作用于多个靶点,具有更高的疗效和更低的耐药性。因此,使用混合化合物来解决目前癌症医学中的难题具有很大的空间。最近的工作已经应用这项技术发现了一些具有显著抗癌特性的有趣分子。在本研究中,我们报告了过去10年(2011 - 2021年)开发的众多有前景的混合抗增殖/抗肿瘤药物的数据。它包括通过分子杂交技术产生的喹唑啉、吲哚、咔唑、嘧啶、喹啉、醌、咪唑、硒、铂、异羟肟酸、二茂铁、姜黄素、三唑、苯并咪唑、异吲哚酮、吡咯并苯并二氮杂卓(PBD)、查尔酮、香豆素、氮芥、吡唑和吡啶基抗癌杂交物。总体而言,本综述清楚地表明了将来自多个不同已知化学原型的药效亚基合并以产生更有效和精确的混合化合物的潜在益处。这为研究癌症等复杂疾病的研究人员提供了有价值的知识。