Synthesis of New Chiral Derivatives of Xanthones with Enantioselective Effect on Tumor Cell Growth and DNA Crosslinking

• Type: Article in International Scientific Journal
• Date: 2020

Authors

Carraro, ML (Author) Other; Marques, S (Author) Other; Silva, AS (Author) Other; Freitas, B (Author) Other; Silva, PMA (Author) Other; Pedrosa, J (Author) Other; De Marco, P (Author) Other; Bousbaa, H (Author) Other; Carla Fernandes (Author) FFUP; Tiritan M.E. (Author) FFUP; Silva, AMS (Author) Other; Pinto, MMM (Author) Other

Journal

Title: ChemistrySelect

Vol. 5

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00S-PFH

DOI: 10.1002/slct.202002588

Abstract (EN): A new series of thirty-two new enantiomerically pure derivatives of xanthones (3-34) were synthesized for antitumor evaluation. Two carboxyxanthones (1and2) were used as chemical substrates and coupled with selected chiral building blocks (43-62), achieving yields and enantiomeric excess (ee) values higher than 92 and 99 %, respectively. Carboxyxanthones1and2were synthesized, by a multi-step synthetic pathwayviadiaryl ether intermediate (Ullman reaction), being compound2described here for the first time. The evaluation of the growth inhibitory activity allowed to find active chiral compounds for all the tested cells lines, and to establish structure-activity relationship (SAR) considerations. In some cases, the growth inhibitory effects demonstrated to be dependent on the stereochemistry of the compounds. Interestingly, the most active compound (12) and its enantiomer (11) demonstrated high enantioselectivity for MCF-7 breast adenocarcinoma cell line. In addition,in vitroDNA crosslinking ability was assessed and the results correlated within vitrocytotoxicity.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7