Lee, Haeun Sawant, Vikram Shahaji Kim, Uhyeok Kim, Jinhyeok Baek, Soo Yeon Lee, Sanghee Choo, Hyunah Kang, Taek Jeon, Byungsun 2025-04-09T07:00:32Z 2025-04-09T07:00:32Z 2025-04-09 2025-04 0253-2964 https://pubs.kist.re.kr/handle/201004/152193 Parkinson's disease (PD) is a progressive neurodegenerative disease caused by a loss of dopaminergic neurons in the substantia nigra. Monoamine oxidase-B (MAO-B) inhibition is a promising strategy for disease modification. Here, we synthesized a series of 2,6-diarylbenzo[d]oxazoles and identified two potent and selective hMAO-B inhibitors: 4,4 '-(benzo[d]oxazole-2,6-diyl)diphenol 4a (IC50 = 0.182 mu M) and 4-(2-(3-fluorophenyl)benzo[d]oxazol-6-yl)phenol 4f (IC50 = 0.184 mu M). Molecular modeling indicated that the benzoxazole core interacts hydrophobically within the active site, contributing to their inhibitory potency. Both compounds demonstrated reversible or partially reversible inhibition of hMAO-B and neuroprotective effects in the MPP+-induced neurotoxicity assay using human neuroblastoma cells. Additionally, both compounds exhibited good microsomal stability and lacked significant perturbation of hERG channel activity. While 4a showed CYP inhibition against some isozymes, 4f had minimal effects on CYP isozyme activities, suggesting a more favorable pharmacokinetic profile. Based on these findings, 4f presents a promising therapeutic candidate for the treatment of PD. English 대한화학회 2,6-Diarylbenzo[d]oxazoles as MAO-B inhibitors for the treatment of Parkinson's disease Article 10.1002/bkcs.70010 1 Bulletin of the Korean Chemical Society, v.46, no.4, pp.422 - 428 Bulletin of the Korean Chemical Society 46 4 422 428 N scie scopus kci ART003195458 001447112600001 2-s2.0-105000267189 Chemistry, Multidisciplinary Chemistry Article MONOAMINE-OXIDASE-B MECHANISM benzoxazole MAO-B neurotoxicity Parkinson&apos s disease selective inhibitor