1,2,3-Triazole-, arylamino- and thio-substituted 1,4-naphthoquinones: Potent antitumor activity, electrochemical aspects, and bioisosteric replacement of C-ring-modified lapachones

Abstract

1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 μM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.

Synthesis and antitumor activity of selenium-containing quinone-based triazoles possessing two redox centres, and their mechanistic insights

“…For the selenium-containing quinones 6 and 10 , the strategy of insertion of a second redox centre was a success and these derivatives were more active than their naphthoquinoidal precursors. Recently, we reported the synthesis and antitumor activities of several α-lapachone-based 1,2,3-triazoles [33]. It is important to highlight that the selenium-containing-based 1,2,3-triazole 7 displayed better activity than the compounds without the chalcogen.…”

“…Para -naphthoquinones 15 and 16 were active against all cancer cell lines studied. In the last few years, we described nor-α-lapachone-based 1,2,3-triazoles obtained from lapachol ( 1 ) with IC 50 values > 2 μM [33]. The strategy herein used to prepare compounds 15 and 16 with the presence of selenium improved the activities of nor-α-lapachone-based 1,2,3-triazoles, and these derivatives presented IC 50 values ranging from 0.68-1.71 μM for 15 , and 1.59-2.95 μM for 16 .…”

“…The approach of inserting a triazole moiety in 1,4-naphthoquinones was also effective, since this unit is known as a potent pharmacophoric group [32]. Recently, 1,4-naphthoquinone-based 1,2,3-triazoles (Scheme 1a) were reported as having high activity in the range of 1.4 to 1.9 μM in HL-60 human promyelocytic leukemia cells [33]. …”

On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells

“…As previously reported, 35 compounds 8-11 were classified according to their cytotoxicity against cancer cells as highly active (IC 50 < 2 µM), moderately active (2 µM < IC 50 < 10 µM), or inactive (IC 50 > 10 µM). As shown in Table 1, no active para-quinones (8-10) were identified.…”

Design, synthesis and antitrypanosomatid activities of 3,5‐diaryl‐isoxazole analogues based on neolignans veraguensin, grandisin and machilin G

“…Tetrahydrofuran neolignans, derived from natural sources, are considered privileged structures as they show several biological activities including antibacterial, antifungal, antitumour and anti‐inflammatory. The tetrahydrofuran neolignans veraguensin ( 1 ), grandisin ( 2 ) and machilin G ( 3 ), for instance (Figure ), have shown antitrypanosomal and antileishmanial activities (Figure ) (Bernardes, Kato, Albuquerque & Carvalho, ; Carvalho et al., ; Da Cruz et al., ; Filho et al., ; Jean‐Moreno, Rojas, Goyeneche, Coombs & Walker, ; Lopes, Chicaro, Albuquerque, Yoshida & Kato, ; Oliveira et al., , ; Schmidt et al., ; Silva Filho et al., ; Verza et al., ).…”