Synthesis, trypanocidal and anti-leishmania activity of new triazole-lapachol and nor-lapachol hybrids

• Published in: Bioorganic chemistry Vol. 103; pp. 104122 - 104127
• Main Authors: Pertino, Mariano Walter, F. de la Torre, Alexander, Schmeda-Hirschmann, Guillermo, Vega, Celeste, Rolón, Miriam, Coronel, Cathia, Rojas de Arias, Antonieta, Leal López, Karla, Carranza-Rosales, Pilar, Viveros Valdez, Ezequiel
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.10.2020; Elsevier
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Antiprotozoal activity; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Biochemistry & Molecular Biology; Cell Line; Chemistry; Chemistry, Organic; Click chemistry; Dose-Response Relationship, Drug; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Lapachol; Leishmania - drug effects; Life Sciences & Biomedicine; Mice; Microbial Sensitivity Tests; Molecular Structure; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; Parasitic Sensitivity Tests; Physical Sciences; Science & Technology; Structure-Activity Relationship; Triazoles - chemistry; Triazoles - pharmacology; Trypanosoma cruzi - drug effects; Lapachol; Antibacterial; Click chemistry; Antiprotozoal activity; NAPHTHOQUINONES; IN-VITRO; DESIGN; TRYPANOSOMA-CRUZI; DRUGS; BIOLOGICAL EVALUATION; RESISTANCE; DERIVATIVES
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2020.104122

[Display omitted] •A new library of twenty lapachol–triazole derivatives was synthesized.•The triazole-naphthoquinone derivatives improve antiprotozoal activity.•Compounds 5b and 5e gave SI of 15.6 and 16.3, respectively against L. braziliensis.•Some compounds showed moderate antibacterial activity against Staphylococcus aureus. A new library of twenty triazole-lapachol and nor-lapachol derivatives was synthesized. The compounds were evaluated against the epimastigotes form of Trypanosoma cruzi and promastigotes of Leishmania braziliensis and L. infantum. The cytotoxicity of the compounds was determined on murine fibroblasts and used to assess the selectivity index. The introduction of triazole rings in the naphthoquinone derivatives improved activity against the parasitic protozoa T. cruzi and Leishmania species. Some of the derivatives were three to six times more potent than benznidazole against T. cruzi, with similar or slightly better selectivity indexes. The results against L. braziliensis showed that the derivatives 5b and 5e were the most selective compounds. However, they were less selective than the reference compound, miltefosine. Among all products, the derivative 3a was the most selective compound against L. infantum. Nevertheless, it was less potent and less selective than miltefosine. Also, the minimum inhibitory concentration values of the derivatives against nine different bacteria were determined. Moderate antibacterial activity was observed for compound 5c against Staphylococcus aureus.