{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T02:01:40Z","timestamp":1784512900846,"version":"3.55.0"},"reference-count":69,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Proyecto Canon Minero","award":["0262\u20132021\/UNT"],"award-info":[{"award-number":["0262\u20132021\/UNT"]}]},{"name":"Fondo Interno VRII-UNAP","award":["UNAP-Consolida 2025"],"award-info":[{"award-number":["UNAP-Consolida 2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The structural hybridization of bioactive quinones is a promising strategy for generating pharmacologically active compounds through sustainable synthetic approaches. This study aimed to synthesize and evaluate a dapsone-derived phenylaminojuglone as a potential intestinal smooth muscle relaxant. Juglone (AJ) was functionalized with dapsone (D) via a solvent-free mechanochemical aza-Michael reaction using silica gel as a mild acid catalyst. The resulting compound (AJ-D) was characterized and evaluated in isolated rat ileum preparations. Pharmacological studies were complemented by molecular docking, density functional theory (DFT) calculations, and in silico ADMET predictions. AJ-D was obtained with complete regioselectivity at the C-3 position and required shorter reaction times than conventional solution-based methods. The compound exhibited significant spasmolytic and antispasmodic effects under basal conditions and against acetylcholine- and KCl-induced contractions. Its relaxant activity was not significantly affected by muscarinic receptor blockade or K+ channel inhibition, whereas verapamil reduced its potency. Calcium reintroduction experiments suggested the involvement of extracellular Ca2+ influx pathways. Docking studies suggested favorable interactions with the CaV1.2 L-type calcium channel, whereas DFT and ADMET analyses indicated suitable electronic and drug-like properties. AJ-D is a promising juglone-derived scaffold with antispasmodic activity, likely associated with the modulation of extracellular calcium influx pathways involved in intestinal smooth muscle contraction.<\/jats:p>","DOI":"10.3390\/biom16071045","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:47:32Z","timestamp":1784508452000},"page":"1045","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Solvent-Free Mechanochemical Synthesis, Antispasmodic Activity, and Integrated In Silico Mechanistic Analysis of a Dapsone-Derived Phenylaminojuglone"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9862-4840","authenticated-orcid":false,"given":"Ricardo E.","family":"Zavaleta-Mi\u00f1ano","sequence":"first","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Estudios de Compuestos Naturales y Sint\u00e9ticos con Actividad a Nivel Sistema Nervioso Central y Musculo Liso, Laboratorio de Farmacolog\u00eda, Facultad de Farmacia y Bioqu\u00edmica, Universidad Nacional de Trujillo, Trujillo 13011, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Mantilla-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Estudios de Compuestos Naturales y Sint\u00e9ticos con Actividad a Nivel Sistema Nervioso Central y Musculo Liso, Laboratorio de Farmacolog\u00eda, Facultad de Farmacia y Bioqu\u00edmica, Universidad Nacional de Trujillo, Trujillo 13011, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0011-7957","authenticated-orcid":false,"given":"Roberto O.","family":"Yba\u00f1ez-Julca","sequence":"additional","affiliation":[{"name":"Grupo de Investigaci\u00f3n en Estudios de Compuestos Naturales y Sint\u00e9ticos con Actividad a Nivel Sistema Nervioso Central y Musculo Liso, Laboratorio de Farmacolog\u00eda, 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