Synthesis and Cytotoxic Evaluation of 1H-1,2,3-Triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones

Abstract

The 1,2-naphthoquinone compound was previously considered active against solid tumors. Moreover, glycosidase inhibitors such as 1,2,3-1H triazoles has been pointed out as efficient compounds in anticancer activity studies. Thus, a series of eleven 1,2-naphthoquinones tethered in C2 to 1,2,3-1H-triazoles 9a-k were designed, synthesized and their cytotoxic activity evaluated using HCT-116 (colon adenocarcinoma), MCF-7 (breast adenocarcinoma) and RPE (human nontumor cell line from retinal epithelium). The chemical synthesis was performed from C-3 allylation of lawsone followed by iodocyclization with subsequent nucleophilic displacement with sodium azide and, finally, the 1,3-dipolar cycloaddition catalyzed by Cu(I) with terminal alkynes led to the formation of 1H-1,2,3-Triazol-1-ylmethyl-2,3-dihydronaphtho[1,2-b]furan-4,5-diones in good yields. Compounds containing aromatic group linked to 1,2,3-triazole ring (9c, 9d, 9e, 9i) presented superior cytotoxic activity against cancer cell lines with IC50 in the range of 0.74 to 4.4 µM indicating that the presence of aromatic rings substituents in the 1,2,3-1H-triazole moiety is probably responsible for the improved cytotoxic activity.

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents

“…1,2-Naphthoquinone-1,2,3-triazole hybrids presenting different substituents on the triazole heterocycle were studied by Chipoline et al [ 58 ]. The synthesis started from the allylation of lawsone, followed by iodocyclization to tetrahydrofuran and further formation of the triazole ring system by the conventional method.…”

Click Chemistry in Natural Product Modification

“…The 1,4-furanaphthoquinone-triazole hybrid M7 (IC 50 : 81.81–99.56 μ M) and its regioisomer 1,2-furanaphthoquinone-triazole hybrid M8 (IC 50 : 23.04–41.10 μ M) could only exhibit moderate inhibitory activity against MDA-MB-231 and CaCo-2 cancer cells ( Costa et al, 2018 ), whereas 1,2-furanaphthoquinone-triazole M9 (IC 50 : 0.74–1.77 μ M) could exert superior cytotoxic activity against HCT-116 and MCF-7 cancer cells ( Chipoline et al, 2018 ), and the selenium version hybrid M10 (IC 50 : 0.07–0.29 μ M) and M11 (IC 50 : 0.07–0.38 μ M) showed high activity against HL-60, PC3, HCT-116, SF295, OVCAR-8, and MDA-MB-435 cancer cell lines ( da Cruz et al, 2016 ). Mechanistic studies revealed that their apoptosis effect was associated with ROS production.…”

Bioactive 1,2,3‐Triazoles: An Account on their Synthesis, Structural Diversity and Biological Applications

“…Also in 2018, Ferreira and da Silva's group reported the selective synthesis and biological evaluation of 1 H ‐1,2,3‐triazol‐1‐ylmethyl‐2,3‐dihydronaphtho[1,2‐ b ]furan‐4,5‐diones 95 [77] . The synthesis of 95 was initiated with the C‐3 alkylation of lawsone ( 89 ) with allyl bromide in basic medium, giving 92 , which next undergoes an intramolecular cyclization, giving iodinated compound 93 , followed by nucleophilic substitution with sodium azide to furnish to the key intermediate 94 with a 78 % overall yield.…”

“…Finally, compounds 95 were synthetized via the CuAAC between azido‐quinone 94 and different alkynes, with yields varying from 35–70 % (Scheme 21). [77] Interestingly, derivatives 95 could also be obtained through a one‐pot reaction from 3‐allyl‐1,4‐naphthoquinone 92 [78] . The cytotoxic activity of 1,2,3‐triazoles 95 was evaluated against the HCT116, MCF‐7 and RPE cell lines, and the observed IC 50 values (0.74–4.38 μM) demonstrated that compounds 95 a – e were the most active ones.…”