Centre for Nano and Material Sciences, Jain (Deemed-To-Be University), Bangalore, Karnataka, India.
Aurigene Pharmaceutical Services, Bangalore, Karnataka, India.
Chem Biol Drug Des. 2024 Aug;104(2):e14609. doi: 10.1111/cbdd.14609.
To increase the success rate of drug discovery, one practical strategy is to begin molecular hybridisation. The presence of two or more pharmacophores in a single unit leads to a pharmacological potency greater than the sum of each individual moiety's potency. Heterocyclic compounds are very widely distributed in nature and are essential for life activities. Benzimidazole and oxadiazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The drug-like properties (like pharmacokinetics and pharmacodynamics) of the individual scaffolds can be improved by benzimidazole-oxadiazole chimeric molecules via a molecular hybridisation approach. Benzimidazole and oxadiazole cores can either be fused or incorporated using either functional groups/bonds. Over the last few decades, drug discovery scientists have predicted that these moieties could be interconnected to yield a novel or modified hybrid compound. Benzimidazole and oxadiazole hybrids were identified as the most potent anticancer, antimicrobial, anti-inflammatory, antioxidant, anticonvulsant, antidepressant, antihypertensive and antitubercular agents. In this context, the present review describes the biological properties of benzimidazole-oxadiazole (1,3,4 and 1,2,4) hybrids, their possible structure-activity relationship and the mechanism of action studies presented. This review article is intended to stimulate fresh ideas in the search for rational designs of more active and less toxic benzimidazole-oxadiazole hybrid prospective therapeutic candidates, as well as more effective diagnostic agents and pathologic probes.
为提高药物发现的成功率,一种实用的策略是开始进行分子杂交。在一个单一单位中存在两个或更多药效团会导致药理活性大于每个单独部分的活性的总和。杂环化合物在自然界中分布非常广泛,是生命活动所必需的。苯并咪唑和恶二唑是药物化学中的优势结构,由于其广泛的生物学特性,它们被广泛用于药物发现和开发中。通过分子杂交方法,可以改善单个支架的药物样性质(如药代动力学和药效学)。苯并咪唑和恶二唑核心可以通过官能团/键融合或结合。在过去的几十年中,药物发现科学家预测,这些部分可以相互连接,产生新的或修饰的杂合化合物。苯并咪唑和恶二唑杂合体被确定为最有效的抗癌、抗菌、抗炎、抗氧化、抗惊厥、抗抑郁、抗高血压和抗结核药物。在这种情况下,本综述描述了苯并咪唑-恶二唑(1,3,4 和 1,2,4)杂合体的生物学性质、它们可能的构效关系以及提出的作用机制研究。本文旨在为寻找更有效、毒性更低的苯并咪唑-恶二唑杂合潜在治疗候选物以及更有效的诊断剂和病理探针提供新的思路。