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.

The actinomycete strain BRA 177 was recovered from sediment samples collected at the St. Peter and St. Paul Archipelago, Brazil. This work accessed the ability of this strain, identified as Actinomadura sp., to produce bioactive metabolites by exploring the genome and characterizing chemistry and cytotoxicity of isolated compounds. From the crude ethyl acetate extract, the pigments nonylprodigiosin, cyclononylprodigiosin and methylcyclooctilprodigiosin were isolated and displayed cytotoxicity against human tumor and non-tumor cell lines. Sequencing, assembling and prospection of BRA 177 draft genome led to identification of two contigs encoding enzymes with high homology to those from prodiginine biosynthetic gene clusters (BGC) in actinomycetes. Further, Actinomadura sp. BGC presented unique putatives RedJ thioesterase and RedL-like type I PKS, involved on selection of prodiginine biosynthetic fatty acyl precursor, and RedG-like Rieske oxygenase, key for cyclization of the prodiginines, suggesting that cyclononilprodigiosin and methylcyclooctylprodigiosin could actually be considered chemical signatures of Actinomadura spp.