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

doi:10.1016/j.isci.2018.04.022

Catalytic Double Cyclization Process for Antitumor Agents against Breast Cancer Cell Lines

iScience. 2018 May 25:3:279-288. doi: 10.1016/j.isci.2018.04.022. Epub 2018 May 3.

Authors

Raffaella Mancuso¹, Ida Ziccarelli², Adele Chimento³, Nadia Marino⁴, Nicola Della Ca'⁵, Rosa Sirianni³, Vincenzo Pezzi³, Bartolo Gabriele⁶

Affiliations

¹ 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. Electronic address: raffaella.mancuso@unical.it.
² 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.
³ Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, 87036 Arcavacata di Rende, Rende (CS), Italy.
⁴ Department of Chemistry and Chemical Technologies, University of Calabria, Via Pietro Bucci 14/C, 87036 Arcavacata di Rende, Rende (CS), Italy.
⁵ Department of Life Sciences and Environmental Sustainability (SCVSA), University of Parma, Parco Area delle Scienze 11/A, 43124 Parma, Italy.
⁶ 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. Electronic address: bartolo.gabriele@unical.it.

Abstract

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.

Keywords: Drugs; Organic Synthesis; Toxicology Evaluation.