Suzuki-Miyaura Coupling between 3-Iodolawsone and Arylboronic Acids. Synthesis of Lapachol Analogues with Antineoplastic and Antileishmanial Activities

Abstract

A series of 2-hydroxy-3-arylnaphthalene-1,4-diones (3-aryllawsones) were synthesized by Suzuki-Miyaura cross coupling reaction of 3-iodolawsone with arylboronic acids/esters. The hydroxylated resulting products were transformed into their corresponding N,N-diethyl carbamates. The antineoplastic and antileishmanial activities of the compounds were evaluated and compared with lapachol and its carbamate, providing promising results.

Low doses of 3-phenyl-lawsone or meglumine antimoniate delivery by tattooing route are successful in reducing parasite load in cutaneous lesions of Leishmania (Viannia) braziliensis-infected hamsters

“…This naphthoquinone presented dose-dependent activity in vitro , as on promastigotes (IC 50 = 116 ± 26 µM, 72h) as well intracellular amastigotes (IC 50 = 193 ± 19 μM, 48h) forms of L. ( V. ) braziliensis. These data corroborate with the previous report from our group, that has shown the in vitro effect of 3-PL against Leishmania ( L. ) amazonensis , in both promastigotes (IC 50 = 85 μM, 72h) and intracellular amastigotes (IC 50 = 25 μM, 72h) forms ( Gomes et al., 2017 ). The ability of 3-PL to have an effect against species of the different subgenus of the Leishmania (subgenus Leishmania and Viannia ), makes it even more promising.…”

“…The differences between the IC 50 values obtained in this study for L. (V.) braziliensis and those reported for L. (L.) amazonensis is expected due to the susceptibility variations between different subgenera and species of Leishmania , as well as the experimental conditions used. We established the IC 50 of 3-PL to L. ( V. ) braziliensis amastigotes at 48h, while IC 50 to L. ( L. ) amazonensis was made at 72h ( Gomes et al., 2017 ). The antileishmanial activity of lapachol, the naphthoquinone precursor molecule of 3-PL, presented wide values of IC 50 dependent on Leishmania strain and experimental conditions.…”

“…The lapachol derivative 3-phenyl-lawsone, 3-PL, ( Figure 1A , insert) was synthesized in the Laboratory of Bioorganic Chemistry of the Federal University of Rio de Janeiro, Brazil by the Suzuki-Miyaura reaction as previously described ( Gomes et al., 2017 ). For assays, the 3-PL was dissolved in DMSO (Sigma Aldrich, St Louis, MO, USA) whose final concentration did not exceed 1%.…”

Lapachol and synthetic derivatives: in vitro and in vivo activities against Bothrops snake venoms

“…The present research was aimed at exploring, for the first time, the activity of lapachol against snake venoms. This prompted us to study the potential activity of the analogues based on the 2-hydroxi-naphthoquinone scaffold, which had been previously synthesized (Fig 1) [31], investigating their effects against some important activities of crude Bothrops atrox and Bothrops jararaca venoms under different experimental protocols in vivo and in vitro .…”

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

“…Some outstanding drug discovery programmes are widely used to find leading compounds, based on and inspired by the molecular modifications of natural products. Recent studies have demonstrated the potential of this approach for the discovery of new chemical entities in the treatment of neglected diseases (Carneiro et al., ; Cassamale et al., ; Costa et al., ; Dubar, Khalife, Brocard, Dive & Biot, ; Ferreira, ; Gomes et al., ; Jardim et al., ; Silva Júnior, Jardim, Menna‐Barreto & Castro, ; Varela et al., ; Zingales et al., ).…”