Improving the Activity of Aminophenoxazinones: Synthesis, CPC Purification, and Phytotoxicity Potential

Aminophenoxazinones (APOs) are potent phytotoxic metabolites and histone deacetylase inhibitors, offering a low-resistance bioherbicide profile. This research synthesized a library of APO derivatives with targeted modifications to optimize physicochemical properties and biological activity using oxidative cyclocondensation. Purification challenges from strong compound-solid phase interactions were overcome by using centrifugal partition chromatography (CPC). Phytotoxicity was screened against Lolium rigidum, Portulaca oleracea, and Plantago lanceolata. While germination remained largely unaffected, compounds 10 and 11 caused significant root inhibition (77% and 89%, respectively for P. oleracea) at 1000 μM. Specifically, 11 reached inhibition levels comparable to the positive control, pendimethalin (86% for P. oleracea). Following a detailed structure-activity relationship analysis, 10 emerged as the most potent candidate, exhibiting an IC₅₀ of 4.5 μM against P. oleracea roots, considerably lower than that of natural APO (332.5 μM). These findings strongly validate this rational design and purification strategy, positioning 10 as a valuable agrochemical lead for sustainable weed management.