Coumarins from Rutaceae: Chemical diversity and biological activities

Santos, Cezar M.; Cardoso, Samara Machado; Sales, Edijane Matos; Velozo, Eudes da Silva; Santosb, Emile Kelly Porto dos; Canuto, Gisele André Baptista; Azeredo, Francine Johansson; Barrosd, Tânia F.; Biegelmeyer, Renata

doi:10.1016/j.fitote.2023.105489

Cited by 6 publications

(1 citation statement)

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“…Thus, for 3D-structure of model prediction, the amino acid sequence of the ten enzymes for L. panamensis were obtained from the UniProt database (UniProtKB 2018 ). For template identification, the enzyme amino acid sequences in FASTA format were submitted to the SWISS-MODEL server (Schwede et al 2003 ; Arnold et al 2006 ) by searching against Protein Data Bank (PDB) proteins to develop a model with sufficient sequence coverage and sequence identity (more than 75%). The sequence which shows high homology to the target sequence was chosen as template (based on the Global Model Quality Estimation (GMQE) and RMSD values).…”

Section: Methodsmentioning

confidence: 99%

3-styrylcoumarin scaffold-based derivatives as a new approach for leishmaniasis intervention: biological and molecular modeling studies

Yepes,

Robledo,

Quintero-Saumeth

et al. 2024

J Parasit Dis

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Seven 3-styrylcoumarins were tested for antileishmanial activity against Leishmania (Viannia) panamensis amastigotes. Cytotoxic activity was also evaluated against mammalian U-937 cells. The 3-methoxy-4-hydroxy coumarin derivative 6 was the most active with an IC50 of 40.5 µM, and did not reveal any conspicuous toxicity toward mammalian U-937 cells. Therefore, it may have potential to be considered as candidate for antileishmanial drug development. Further, among several druggable Leishmania targets, molecular docking studies revealed that compound 6 had docking preference by the N-myristoyltransferase (Lp-NMT) of Leishmania panamensis, showing a higher docking score of − 10.1 kcal mol−1 than positive controls and making this protein as a presumably druggable target for this compound. On the other hand, molecular dynamics simulations affirm the docking hypothesis, showing a conformational stability of the 6/Lp-NMT complex throughout 100 ns simulation. Moreover, the molecular mechanics/Poisson–Boltzmann surface area method also support the docking findings, revealing a total free energy of binding of − 47.26 ± 0.08 kcal mol−1, and identifying through energy decomposition analysis that those key aminoacids are contributing strongly to ligand binding. Finally, an optimal pharmacokinetic profile was also estimated for 6. Altogether, coumarin 6 could be addressed as starting point for further pharmacological studies concerning the therapeutic leishmaniasis intervention. Graphical abstract

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Section: Methodsmentioning

confidence: 99%