Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani Campus, Pilani, 333031, Rajasthan, India.
Chem Biodivers. 2023 Aug;20(8):e202300587. doi: 10.1002/cbdv.202300587. Epub 2023 Jul 11.
The use of privileged scaffolds has proven beneficial for generating novel bioactive scaffolds in drug discovery program. Chromone is one such privileged scaffold that has been exploited for designing pharmacologically active analogs. The molecular hybridization technique combines the pharmacophoric features of two or more bioactive compounds to avail a better pharmacological activity in the resultant hybrid analogs. The current review summarizes the rationale and techniques involved in developing hybrid analogs of chromone, which show potential in fields of obesity, diabetes, cancer, Alzheimer's disease and microbial infections. Here the molecular hybrids of chromone with various pharmacologically active analogs or fragments (donepezil, tacrine, pyrimidines, azoles, furanchalcones, hydrazones, quinolines, etc.) are discussed with their structure-activity relationship against above-mentioned diseases. Detailed methodologies for the synthesis of corresponding hybrid analogs have also been described, with suitable synthetic schemes. The current review will shed light on various strategies utilized for the design of hybrid analogs in the field of drug discovery. The importance of hybrid analogs in various disease conditions is also illustrated.
特权支架的使用已被证明有利于在药物发现计划中生成新型生物活性支架。色酮就是这样一种特权支架,它已被用于设计具有药理活性的类似物。分子杂交技术结合了两个或多个生物活性化合物的药效特征,以使所得杂交类似物具有更好的药理活性。本综述总结了开发色酮的杂交类似物的原理和技术,这些类似物在肥胖症、糖尿病、癌症、阿尔茨海默病和微生物感染等领域显示出潜力。本文讨论了色酮与各种具有药理活性的类似物或片段(多奈哌齐、他克林、嘧啶、唑类、呋喃查尔酮、腙、喹啉等)的分子杂合体及其对上述疾病的构效关系。还描述了相应的杂合类似物的合成方法,包括合适的合成方案。本综述将阐明药物发现领域中设计杂合类似物所采用的各种策略。还说明了杂合类似物在各种疾病情况下的重要性。