In Vitro Antiproliferative Evaluation of Synthetic Meroterpenes Inspired by Marine Natural Products
The NeaNat Group, Department of Pharmacy, University of Naples “Federico II”, Via D. Montesano 49, 80131 Napoli, Italy
Laboratory of Pre-Clinical and Translational Research, IRCCS-CROB, Referral Cancer Center of Basilicata, 85028 Rionero in Vulture, Italy
Department of Clinical and Experimental Medicine, University of Foggia, via L. Pinto c/o OO.RR., 71100 Foggia, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Mar. Drugs 2019, 17(12), 684; https://doi.org/10.3390/md17120684
Received: 20 November 2019 / Revised: 2 December 2019 / Accepted: 4 December 2019 / Published: 5 December 2019
(This article belongs to the Special Issue Synthesis of Marine Natural Products and Molecules Inspired by Marine Substances)
Several marine natural linear prenylquinones/hydroquinones have been identified as anticancer and antimutagenic agents. Structure-activity relationship studies on natural compounds and their synthetic analogs demonstrated that these effects depend on the length of the prenyl side chain and on the type and position of the substituent groups in the quinone moiety. Aiming to broaden the knowledge of the underlying mechanism of the antiproliferative effect of these prenylated compounds, herein we report the synthesis of two quinones 4 and 5 and of their corresponding dioxothiazine fused quinones 6 and 7 inspired to the marine natural product aplidinone A (1), a geranylquinone featuring the 1,1-dioxo-1,4-thiazine ring isolated from the ascidian Aplidium conicum. The potential effects on viability and proliferation in three different human cancer cell lines, breast adenocarcinoma (MCF-7), pancreas adenocarcinoma (Bx-PC3) and bone osteosarcoma (MG-63), were investigated. The methoxylated geranylquinone 5 exerted the highest antiproliferative effect exhibiting a comparable toxicity in all three cell lines analyzed. Interestingly, a deeper investigation has highlighted a cytostatic effect of quinone 5 referable to a G0/G1 cell-cycle arrest in BxPC-3 cells after 24 h treatment.