Antiparasitary and antiproliferative activities in vitro of a 1,2,4-oxadiazole derivative on Trypanosoma cruzi

Rocha, Yasmim Mendes; Magalhães, Emanuel Paula; Chaves, Marlos de Medeiros; Marinho, Márcia Machado; Oliveira, Valentina Nascimento e Melo de; Oliveira, Ronaldo N. de; Sampaio, Tiago Lima; Menezes, Ramon Róseo Paula Pessoa Bezerra de; Martins, Alice Maria Costa; Nicolete, Roberto

doi:10.1007/s00436-022-07554-z

Cited by 3 publications

(1 citation statement)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some of these fragments can be linked to tremendous recent literature, for example bit 388 corresponds to a 1,2,4-oxadiazole ring. 1,2,4-Oxadiazole-derivatives have been largely neglected by medicinal chemistry until 2005, but in the past 15 years, research has grown exponentially 113 and only in 2022 researchers reported cytotoxic, 114 fungicidal, 115 anti-inflammatory, 114 antiparasitary and antiproliferative 116 effects of 1,2,4-oxadiazole derivatives.…”

Section: Resultsmentioning

confidence: 99%

Chemical representation learning for toxicity prediction

et al. 2023

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Chemical representation learning for toxicity prediction

et al. 2023

View full text Add to dashboard Cite

show abstract

Design, Synthesis, and In Vitro and In Silico Evaluation of 1,3,4‐Oxadiazoles as Anti‐Trypanosoma cruzi and Anti‐Leishmania mexicana Agents

Delgado‐Maldonado,

Moreno‐Rodríguez,

González‐Morales

et al. 2024

ChemMedChem

View full text Add to dashboard Cite

A series of novel 4‐acetyl‐1,3,4‐oxadiazole derivatives was designed and synthesized for their biological evaluation in vitro against Trypanosoma cruzi and Leishmania mexicana. Additionally, compounds were evaluated by molecular docking on the cruzain of T. cruzi (TcCz) and the cysteine protease B (CPB) of L. mexicana (LmCPB) to know their potential mechanism of binding. Compound OX‐12 had better trypanocidal activity against NINOA (IC50= 10.5 µM) and A1 (IC50= 21.7 µM) T. cruzi strains that reference drug benznidazole (IC50= 30.3 µM and 39.8 µM, respectively). Compound OX‐2 had the best biological activity against L. mexicana in M379 (IC50= 11.9 µM) and FCQEPS (IC50= 34.0 µM) strains that the reference drug glucantime (IC50 ˃120 µM). All the compounds showed important interactions with residues on the active site of TcCz (Gly66, Trp26, Leu67, and Ala138) and LmCPB (Gly67, Asn62, Leu68, and Ala140). Finally, the molecular dynamics simulations of the compound OX‐12 shown moderate stability from 40 to 115 ns with an RMSD value of 6.5 Å. Meanwhile, compound OX‐2 showed a minor stability in complex with CPB from 25 to 200 ns of simulation (RMSD <9 Å). These results encourage to develop more potent and efficient trypanocidal and leishmanicidal agents using the 1,3,4‐oxadiazole scaffold.

show abstract

Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi

Rocha,

de Moura,

Rodrigues

et al. 2024

CCHTS

View full text Add to dashboard Cite

Background: Chagas disease kills around 10,000 people yearly, primarily in Latin America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe, and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic compounds as bioisosteres are well known, and they are prospective candidates in the hunt for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease cruzain from T. cruzi is a validated target for disease treatment. Objective: Thus, using a molecular dynamics simulation, the current study attempted to determine if a significant interaction occurred between the enzyme cruzain and its ligand. Results: Interactions with the catalytic site and other critical locations were observed. Also, the RMSD values suggested that the molecule under research had stable interactions with its target. Conclusion: Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic activity of cruzain, indicating that it might be a promising antichagasic drug.

show abstract

Antiparasitary and antiproliferative activities in vitro of a 1,2,4-oxadiazole derivative on Trypanosoma cruzi

Cited by 3 publications

References 65 publications

Chemical representation learning for toxicity prediction

Chemical representation learning for toxicity prediction

Design, Synthesis, and In Vitro and In Silico Evaluation of 1,3,4‐Oxadiazoles as Anti‐Trypanosoma cruzi and Anti‐Leishmania mexicana Agents

Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi

Contact Info

Product

Resources

About