title: Dihydrobenzofuran Neolignanamides: Laccase-Mediated Biomimetic Synthesis and Antiproliferative Activity.
abstract: The biomimetic synthesis of a small library of dihydrobenzofuran neolignanamides (the natural trans-grossamide (4) and the related compounds 21-28) has been carried out through an eco-friendly oxidative coupling reaction mediated by Trametes versicolor laccase. These products, after complete spectroscopic characterization, were evaluated for their antiproliferative activity against Caco-2 (colon carcinoma), MCF-7 (mammary adenocarcinoma), and PC-3 (prostate cancer) human cells, using an MTT bioassay. The racemic neolignamides (±)-21 and (±)-27, in being the most lipophilic in the series, were potently active, with GI50 values comparable to or even lower than that of the positive control 5-FU. The racemates were resolved through chiral HPLC, and the pure enantiomers were subjected to ECD measurements to establish their absolute configurations at C-2 and C-3. All enantiomers showed potent antiproliferative activity, with, in particular, a GI50 value of 1.1 μM obtained for (2R,3R)-21. The effect of (±)-21 on the Caco-2 cell cycle was evaluated by flow cytometry, and it was demonstrated that (±)-21 exerts its antiproliferative activity by inducing cell cycle arrest and apoptosis.
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Nunzio
authors: N
authors: Cardullo
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Luana
authors: L
authors: Pulvirenti
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Carmela
authors: C
authors: Spatafora
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Nicolò
authors: N
authors: Musso
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Vincenza
authors: V
authors: Barresi
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Daniele Filippo
authors: DF
authors: Condorelli
authors: Dipartimento di Scienze Chimiche and ‡Dipartimento di Scienze Biomediche e Biotecnologiche, Sezione di Biochimica Medica, Università degli Studi di Catania , Viale A. Doria 6, I-95125 Catania, Italy.
authors: Corrado
authors: C
authors: Tringali
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D032701:Biomimetics; D018938:Caco-2 Cells; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D042845:Laccase / Q000378:metabolism*; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D001572:Benzofurans; D017705:Lignans; D042845:Laccase; D005472:Fluorouracil