Hassan, Ahmed H. E. Kim, Hyeon Jeong Gee, Min Sung Park, Jong-Hyun Jeon, Hye Rim Lee, Cheol Jung Choi, Yeonwoo Moon, Suyeon Lee, Danbi Lee, Jong Kil Park, Ki Duk Lee, Yong Sup 2024-01-19T10:33:53Z 2024-01-19T10:33:53Z 2022-04-05 2022-12 1475-6366 https://pubs.kist.re.kr/handle/201004/114276 Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed. A library of analogues of the natural product hispidol was prepared and evaluated for inhibition of monoamine oxidases (MAOs) isoforms. Several molecules emerged as selective potential MAO B inhibitors. The most promising compounds were further evaluated in vitro for their impact on microglia viability, induced production of proinflammatory mediators and MAO-B inhibition mechanism. Amongst tested compounds, 1p was a safe potent competitive reversible MAO-B inhibitor and inhibitor of microglial production of neuroinflammatory mediators; NO and PGE(2). In-silico study provided insights into molecular basis of the observed selective MAO B inhibition. This study presents compound 1p as a promising lead compound for management of neurodegenerative disease. English Taylor & Francis Positional scanning of natural product hispidol's ring-B: discovery of highly selective human monoamine oxidase-B inhibitor analogues downregulating neuroinflammation for management of neurodegenerative diseases Article 10.1080/14756366.2022.2036737 1 Journal of Enzyme Inhibition and Medicinal Chemistry, v.37, no.1, pp.768 - 780 Journal of Enzyme Inhibition and Medicinal Chemistry 37 1 768 780 Y scie scopus 000760544300001 2-s2.0-85125213739 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article PSYCHIATRIC-DISORDERS PARKINSONS-DISEASE DRUG DISCOVERY NITRIC-OXIDE DERIVATIVES AURONES DESIGN OPPORTUNITIES MICROGLIA TARGETS Natural products analogues MAO-B inhibitors neuroinflammation neurodegenerative diseases Parkinson&apos s disease