Catalytic Double Cyclization Process for Antitumor Agents against Breast Cancer Cell Lines
Raffaella Mancuso,
Ida Ziccarelli,
Adele Chimento,
Nadia Marino,
Nicola Della Ca’,
Rosa Sirianni,
Vincenzo Pezzi,
Bartolo Gabriele
Affiliations
Raffaella Mancuso
Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci 12/C, 87036 Arcavacata di Rende, Rende (CS), Italy; Corresponding author
Ida Ziccarelli
Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci 12/C, 87036 Arcavacata di Rende, Rende (CS), Italy
Adele Chimento
Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Rende (CS), Italy
Nadia Marino
Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci 14/C, 87036 Arcavacata di Rende, Rende (CS), Italy
Nicola Della Ca’
Department of Life Sciences and Environmental Sustainability (SCVSA), University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy
Rosa Sirianni
Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Rende (CS), Italy
Vincenzo Pezzi
Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Rende (CS), Italy
Bartolo Gabriele
Laboratory of Industrial and Synthetic Organic Chemistry (LISOC), Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci 12/C, 87036 Arcavacata di Rende, Rende (CS), Italy; Corresponding author
Summary: The development of efficient synthetic strategies for the discovery of novel antitumor molecules is a major goal in current research. In this context, we report here a catalytic double cyclization process leading to bicyclic heterocycles with significant antitumor activity on different human breast cancer (BC) cell lines. The products, 6,6a-dihydrofuro[3,2-b]furan-2(5H)-ones, were obtained in one step, starting from simple substrates (4-yne-1,3-diols, CO, and O2), under the catalytic action of PdI2 in conjunction with KI. These compounds have significant antiproliferative activity in vitro on human BC cell lines, both hormone receptor positive (MCF-7) and triple negative (triple-negative breast cancer [TNBC]; MDA-MB-231 and MDAMB-468), while exhibiting practically no effects on normal MCF-10A (human mammary epithelial) and 3T3-L1 (murine fibroblasts) cells. Thus, these compounds have the potential to expand the therapeutic options against BC, and in particular, against its most aggressive forms (TNBCs). Moreover, the present synthetic approach may provide an economic benefit for their production. : Drugs; Organic Synthesis; Toxicology Evaluation Subject Areas: Drugs, Organic Synthesis, Toxicology Evaluation
