Month 2019 Efficient Synthesis of New 2H-Chromene Retinoids Hybrid Derivatives by Suzuki Cross-coupling Reactions Asma Kaoukabi, a * Larbi Belachemi, a Mohammed Lahcini, a Marie-Claude Viaud Massuard, b and Cécile Croix b a Laboratory of Organometallic and Macromolecular Chemistry—Composites Materials, Department of Chemistry, Faculty of Sciences and Technology, University Cadi Ayyad of Marrakech, Marrakesh, Morocco b CNRS UMR 7292 GICC, Molecular and Therapeutical Innovation, University of Tours, 31, Avenue Monge, Tours, France *E-mail: kaoukabi1985@gmail.com Received May 24, 2018 DOI 10.1002/jhet.3478 Published online 00 Month 2019 in Wiley Online Library (wileyonlinelibrary.com). In an attempt to improve anticancer activity, a series of retinoids–chromene hybrids was described. The novel heterocyclic chromene–retinoids hybrid including oxygen as a heteroatom in a six-membered cyclic ring (2H-chromene or 2H-1-benzopyran) was designed and synthesized by introducing different groups such as an aromatic or styrylphenyl ring in 6-position of 2H-chromene. These novel compounds were syn- thesized by using the efficient cascades one-pot process involving Wittig–Horner–Emmons reaction and Suzuki–Miyaura cross-coupling pallado-catalyzed reactions with 60% to 90% overall yields. These new compounds were tested against glioblastoma multiforme brain cancer, medulloblastoma, neuroblastoma cell lines, and breast cancer MCF-7 cell lines. Two of them exhibited an appreciable anti-tumor activity in the low micromolar range, which opens new perspectives for therapeutic application on humans. J. Heterocyclic Chem., 00, 00 (2019). INTRODUCTION Retinoids are analogs of all-trans-retinoic acid (ATRA), a powerful hormone that mediates many fundamental biological processes. Most of the physiological actions of retinoids can be accounted by the transcriptional regulatory activity of ATRA and 9-cis RA (9-CRA) through their nuclear receptors, known as RA receptors (RARs), (bind ATRA and 9-CRA), and retinoid X receptors (bind 9-CRA) [1], which associate with RA response elements within the promoters of retinoid- responsive genes [2]. A number of synthetic retinoids that interact selectively with their receptors have been synthesized [3–6]. These ATRA analogs have been synthesized with the aim of improving the therapeutic efficacy, to toxicity index as well as to secure better selectivity for various therapeutic applications. These analogs involve changes in the lipophilic or the hydrophilic part, the spacer, or a combination of changes in the parent compound ATRA [7]. Cancer and other serious hyperproliferative diseases are attractive therapeutic targets for retinoids [8–11]. However, the therapeutic use of retinoids is limited due to their severe © 2019 Wiley Periodicals, Inc.