Hassan, Ahmed H. E. Choi, Yeonwoo Kim, Rium Kim, Hyeon Jeong Almatary, Aya M. El-Sayed, Selwan M. Lee, Yeongae Lee, Jong Kil Park, Ki Duk Lee, Yong Sup 2024-07-26T04:30:09Z 2024-07-26T04:30:09Z 2024-07-25 2024-08 0968-0896 https://pubs.kist.re.kr/handle/201004/150289 Design, synthesis, and biological evaluation of two series of O-4 '-benzyl-hispidol derivatives and the analogous corresponding O-3 '-benzyl derivatives aiming to develop selective monoamine oxidase-B inhibitors endowed with anti-neuroinflammatory activity is reported herein. The first O-4 '-benzyl-hispidol derivatives series afforded several more potentially active and MAO-B inhibitors than the O(3 '-)benzyl derivatives series. The most potential compound 2e of O-4 '-benzyl derivatives elicited sub-micromolar MAO-B IC(50 )of 0.38 mu M with a selectivity index >264 whereas most potential compound 3b of O-3 '-benzyl derivatives showed only 0.95 MAO-B IC(50 )and a selectivity index >105. Advancement of the most active compounds showing sub-micromolar activities to further cellular evaluations of viability and induced production of pro-neuroinflammatory mediators confirmed compound 2e as a potential lead compound inhibiting the production of the neuroinflammatory mediator nitric oxide significantly by microglial BV2 cells at 3 mu M concentration without significant cytotoxicity up to 30 mu M. In silico molecular docking study predicted plausible binding modes with MAO enzymes and provided insights at the molecular level. Overall, this report presents compound 2e as a potential lead compound to develop potential multifunctional compounds. English Pergamon Press Ltd. Synthesis and biological evaluation of O4′-benzyl-hispidol derivatives and analogs as dual monoamine oxidase-B inhibitors and anti-neuroinflammatory agents Article 10.1016/j.bmc.2024.117826 1 Bioorganic & Medicinal Chemistry, v.110 Bioorganic & Medicinal Chemistry 110 N scie scopus 001270374700001 2-s2.0-85198388065 Biochemistry & Molecular Biology Chemistry, Medicinal Chemistry, Organic Biochemistry & Molecular Biology Pharmacology & Pharmacy Chemistry Article NATURAL-PRODUCTS DRUG DISCOVERY MANAGEMENT RECEPTOR DESIGN Natural products derivatives Hybrid molecules Hispidol MAO -B Anti-neuroinflammatory