Anais da Academia Brasileira de Ciências (May 2024)

Design, synthesis and identification of novel molecular hybrids based on naphthoquinone aromatic hydrazides as potential trypanocide and leishmanicidal agents

  • ROSANE D. CEZAR,
  • ADRIANO O. DA SILVA,
  • ROSÂNGELA S. LOPES,
  • CELSO V. NAKAMURA,
  • JEAN HENRIQUE S. RODRIGUES,
  • ESTELA MARIANA G. LOURENÇO,
  • SUMBAL SABA,
  • ADILSON BEATRIZ,
  • JAMAL RAFIQUE,
  • DÊNIS P. DE LIMA

DOI
https://doi.org/10.1590/0001-3765202420230375
Journal volume & issue
Vol. 96, no. 2

Abstract

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Abstract In pursuit of potential agents to treat Chagas disease and leishmaniasis, we report the design, synthesis, and identification novel naphthoquinone hydrazide-based molecular hybrids. The compounds were subjected to in vitro trypanocide and leishmanicidal activities. N’-(1,4-Dioxo-1,4-dihydronaphthalen-2-yl)-3,5-dimethoxybenzohydrazide (13) showed the best performance against Trypanosoma cruzi (IC50 1.83 µM) and Leishmania amazonensis (IC50 9.65 µM). 4-Bromo-N’-(1,4-dioxo-1,4-dihydronaphthalen-2-yl)benzohydrazide (16) exhibited leishmanicidal activity (IC50 12.16 µM). Regarding trypanocide activity, compound 13 was low cytotoxic to LLC-MK2 cells (SI = 95.28). Furthermore, through molecular modeling studies, the cysteine proteases cruzain, rhodesain and CPB2.8 were identified as the potential biological targets.

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