TY - JOUR
T1 - Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis and In Vitro Efficacy
AU - Goyzueta-Mamani, Luis Daniel
AU - Pagliara Lage, Daniela
AU - Barazorda-Ccahuana, Haruna Luz
AU - Paco-Chipana, Margot
AU - Candia-Puma, Mayron Antonio
AU - Davila-Del-Carpio, Gonzalo
AU - Galdino, Alexsandro Sobreira
AU - Machado-de-Avila, Ricardo Andrez
AU - Cordeiro Giunchetti, Rodolfo
AU - D’Antonio, Edward L.
AU - Ferraz Coelho, Eduardo Antonio
AU - Chávez-Fumagalli, Miguel Angel
N1 - Publisher Copyright:
© 2025 by the authors.
PY - 2025/1
Y1 - 2025/1
N2 - Leishmaniasis, a neglected tropical disease caused by Leishmania species, presents serious public health challenges due to limited treatment options, toxicity, high costs, and drug resistance. In this study, the in vitro potential of malvidin and echioidinin is examined as antileishmanial agents against L. amazonensis, L. braziliensis, and L. infantum, comparing their effects to amphotericin B (AmpB), a standard drug. Malvidin demonstrated greater potency than echioidinin across all parasite stages and species. Against L. amazonensis, malvidin’s IC50 values were 197.71 ± 17.20 µM (stationary amastigotes) and 258.07 ± 17 µM (axenic amastigotes), compared to echioidinin’s 272.99 ± 29.90 μM and 335.96 ± 19.35 μM. AmpB was more potent, with IC50 values of 0.06 ± 0.01 µM and 0.10 ± 0.03 µM. Malvidin exhibited lower cytotoxicity (CC50: 2920.31 ± 80.29 µM) than AmpB (1.06 ± 0.12 µM) and a favorable selectivity index. It reduced infection rates by 35.75% in L. amazonensis-infected macrophages. The in silico analysis revealed strong binding between malvidin and Leishmania arginase, with the residues HIS139 and PRO258 playing key roles. Gene expression analysis indicated malvidin’s modulation of oxidative stress and DNA repair pathways, involving genes like GLO1 and APEX1. These findings suggest malvidin’s potential as a safe, natural antileishmanial compound, warranting further in vivo studies to confirm its therapeutic efficacy and pharmacokinetics in animal models.
AB - Leishmaniasis, a neglected tropical disease caused by Leishmania species, presents serious public health challenges due to limited treatment options, toxicity, high costs, and drug resistance. In this study, the in vitro potential of malvidin and echioidinin is examined as antileishmanial agents against L. amazonensis, L. braziliensis, and L. infantum, comparing their effects to amphotericin B (AmpB), a standard drug. Malvidin demonstrated greater potency than echioidinin across all parasite stages and species. Against L. amazonensis, malvidin’s IC50 values were 197.71 ± 17.20 µM (stationary amastigotes) and 258.07 ± 17 µM (axenic amastigotes), compared to echioidinin’s 272.99 ± 29.90 μM and 335.96 ± 19.35 μM. AmpB was more potent, with IC50 values of 0.06 ± 0.01 µM and 0.10 ± 0.03 µM. Malvidin exhibited lower cytotoxicity (CC50: 2920.31 ± 80.29 µM) than AmpB (1.06 ± 0.12 µM) and a favorable selectivity index. It reduced infection rates by 35.75% in L. amazonensis-infected macrophages. The in silico analysis revealed strong binding between malvidin and Leishmania arginase, with the residues HIS139 and PRO258 playing key roles. Gene expression analysis indicated malvidin’s modulation of oxidative stress and DNA repair pathways, involving genes like GLO1 and APEX1. These findings suggest malvidin’s potential as a safe, natural antileishmanial compound, warranting further in vivo studies to confirm its therapeutic efficacy and pharmacokinetics in animal models.
KW - antileishmanial activity
KW - arginase inhibition
KW - cytotoxicity
KW - echioidinin
KW - leishmaniasis
KW - malvidin
UR - http://www.scopus.com/inward/record.url?scp=85214491602&partnerID=8YFLogxK
U2 - 10.3390/molecules30010173
DO - 10.3390/molecules30010173
M3 - Article
AN - SCOPUS:85214491602
SN - 1420-3049
VL - 30
JO - Molecules
JF - Molecules
IS - 1
M1 - 173
ER -