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Open AccessArticle

Design, Synthesis and Cancer Cell Growth Inhibition Evaluation of New Aminoquinone Hybrid Molecules

Laboratory of Bioorganic Chemistry, Department of Physics, University of Trento, Via Sommarive 14, 38123 Trento, Italy
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Academic Editors: Carla Boga and Gabriele Micheletti
Molecules 2019, 24(12), 2224; https://doi.org/10.3390/molecules24122224
Received: 4 June 2019 / Revised: 11 June 2019 / Accepted: 12 June 2019 / Published: 14 June 2019
(This article belongs to the Special Issue Design and Synthesis of Organic Molecules as Antineoplastic Agents)
Molecular hybridization has proven to be a successful multi-target strategy in the design and development of new antitumor agents. Based on this rational approach, we have planned hybrid molecules containing covalently linked pharmacophoric units, present individually in compounds acting as inhibitors of the cancer protein targets tubulin, human topoisomerase II and ROCK1. Seven new molecules, selected by docking calculation of the complexes with each of the proteins taken into consideration, have been efficiently synthesized starting from 2,3-dichloro-1,4-naphtoquinone or 6,7-dichloro-5,8-quinolinquinone. By screening the full National Cancer Institute (NCI) panel, including 60 human cancer cell lines, four molecules displayed good and sometimes better growth inhibition GI50 than the ROCK inhibitor Y-27632, the Topo II inhibitor podophyllotoxin and the tubulin inhibitor combretastatin A-4. The relative position of N,N heteroatoms in the structures of the tested compounds was crucial in affecting bioactivity and selectivity. Furthermore, compound 3 (2-(4-(2-hydroxyethyl)piperazin-1-yl)-3-(3,4,5-trimethoxyphenoxy)naphthalene-1,4-dione) emerged as the most active in the series, showing a potent and selective inhibition of breast cancer BT-549 cells (GI50 < 10 nM). View Full-Text
Keywords: hybrid molecules; quinolinequinones; naphtoquinones; 3,4,5-trimethoxyphenyl group; docking calculation; antitumor activity; cytotoxicity hybrid molecules; quinolinequinones; naphtoquinones; 3,4,5-trimethoxyphenyl group; docking calculation; antitumor activity; cytotoxicity
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MDPI and ACS Style

Defant, A.; Mancini, I. Design, Synthesis and Cancer Cell Growth Inhibition Evaluation of New Aminoquinone Hybrid Molecules. Molecules 2019, 24, 2224.

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