Synthesis and cytotoxic activity of non-naturally substituted 4-oxycoumarin derivatives.
Coumarins are a large family of natural and synthetic compounds exerting different pharmacological effects, including cytotoxic, anti-inflammatory or antimicrobial. In the present communication we report the synthesis of a series of 12 diversely substituted 4-oxycoumarin derivatives including methoxy substituted 4-hydroxycoumarins, methyl, methoxy or unsubstituted 3-aryl-4-hydroxycoumarins and 4-benzyloxycoumarins and their anti-proliferative effects on breast adenocarcinoma cells (MCF-7), human promyelocytic leukemia cells (HL-60), human histiocytic lymphoma cells (U937) and mouse neuroblastoma cells (Neuro2a). The most potent bioactive molecule was the 4-hydroxy-5,7-dimethoxycoumarin (compound 1) which showed similar potency (IC(50) 0.2-2 μM) in all cancer cell lines tested. This non-natural product reveals a simple bioactive scaffold which may be exploited in further studies.
Dipartimento di Scienze della Vita e dell'Ambiente, Sezione di Scienze del Farmaco, Università degli Studi di Cagliari, Via Ospedale 72, 09124 Cagliari, Italy. silvserra@tiscali.it
Silvia
S
Serra
Andrea
A
Chicca
Giovanna
G
Delogu
Saleta
S
Vázquez-Rodríguez
Lourdes
L
Santana
Eugenio
E
Uriarte
Laura
L
Casu
Jürg
J
Gertsch
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D020298:U937 Cells
D000970:Antineoplastic Agents; D003374:Coumarins