Design, synthesis and identification of novel molecular hybrids based on naphthoquinone aromatic hydrazides as potential trypanocide and leishmanicidal agents.
An Acad Bras Cienc
; 96(2): e20230375, 2024.
Article
in En
| MEDLINE
| ID: mdl-38747836
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trypanocidal Agents
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Trypanosoma cruzi
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Drug Design
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Naphthoquinones
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Hydrazines
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Leishmania
Limits:
Animals
Language:
En
Journal:
An Acad Bras Cienc
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: