Molecular interaction assays in silico of crotapotin from Crotalus durissus terrificus against the molecular target trypanothione reductase from Leishmania braziliensis DOI Creative Commons
Jamile Mariano Macedo, M. F. V. Souza,

Anderson Maciel de Lima

и другие.

˜The œJournal of venomous animals and toxins including tropical diseases, Год журнала: 2025, Номер 31

Опубликована: Янв. 1, 2025

Abstract Background: Leishmaniasis is a neglected disease that mainly affects impoverished populations and receives limited attention from governments research institutions. Current treatments are based on antimonial therapies, which present high toxicity cause significant side effects, such as cardiotoxicity hepatotoxicity. This study proposes using crotapotin, isolated Crotalus durissus terrificus venom, potential inhibitor of the enzyme trypanothione reductase Leishmania braziliensis (LbTR). Methods: In silico assays were conducted to evaluate interaction crotapotin with LbTR molecular docking dynamics techniques. Recombinant was expressed in E. coli, its enzymatic activity confirmed. The inhibitory action then tested assays. Results: stability these interactions confirmed over 200 ns simulations, clustering analysis GROMACS method revealing total 12 distinct clusters. five most representative clusters showed low RMSD values, indicating structural LbTR-crotapotin complex. particular, cluster 1, 3,398 frames an average 0.189 nm centroid, suggests dominant stable conformation Additional maintained values between 0.173 0.193 nm, further reinforcing robustness complex under physiological conditions. expression successful, yielding 4.8 mg/L purity, verified by SDS-PAGE. assays, partially inhibited activity, IC50 223.4 μM. Conclusion: findings suggest structured LbTR, fluctuation, although inhibition observed vitro moderate. These results indicate promising basis for developing specific inhibitors, contributing bioprospecting new antiparasitic agents.

Язык: Английский

Extracellular Vesicles during TriTryps infection: Complexity and future challenges DOI
Izadora Volpato Rossi,

Maria Alice Ferreira Nunes,

Sandra Vargas-Otalora

и другие.

Molecular Immunology, Год журнала: 2021, Номер 132, С. 172 - 183

Опубликована: Фев. 15, 2021

Язык: Английский

Процитировано

21
Drug Repurposing in Chagas Disease: Chloroquine Potentiates Benznidazole Activity against Trypanosoma cruzi In Vitro and In Vivo DOI
Ramendra Pati Pandey, Marilda Savóia Nascimento, Caio Haddad Franco

и другие.

Antimicrobial Agents and Chemotherapy, Год журнала: 2022, Номер 66(11)

Опубликована: Окт. 31, 2022

Drug combinations and drug repurposing have emerged as promising strategies to develop novel treatments for infectious diseases, including Chagas disease. In this study, we aimed investigate whether the repurposed drugs chloroquine (CQ) colchicine (COL), known inhibit Trypanosoma cruzi infection in host cells, could boost anti- T. effect of trypanocidal benznidazole (BZN), increasing its therapeutic efficacy while reducing dose needed eradicate parasite. The combination BZN COL exhibited cytotoxicity infected cells low antiparasitic activity.

Язык: Английский

Процитировано

15
Computer-aided drug design approaches applied to screen natural product’s structural analogs targeting arginase in Leishmania spp DOI Creative Commons
Haruna Luz Barazorda-Ccahuana, Luis Daniel Goyzueta-Mamani, Mayron Antonio Candia-Puma

и другие.

F1000Research, Год журнала: 2023, Номер 12, С. 93 - 93

Опубликована: Май 24, 2023

Introduction: Leishmaniasis is a disease with high mortality rates and approximately 1.5 million new cases each year. Despite the approaches advances to fight disease, there are no effective therapies. Methods: Hence, this study aims screen for natural products' structural analogs as drug candidates against leishmaniasis. We applied Computer-aided design (CADD) approaches, such virtual screening, molecular docking, dynamics simulation, mechanics-generalized Born surface area (MM-GBSA) binding free estimation, energy perturbation (FEP) aiming select from products that have shown anti-leishmanial anti-arginase activities could bind selectively Leishmania arginase enzyme. Results: The compounds 2H-1-benzopyran, 3,4-dihydro-2-(2-methylphenyl)-(9CI), echioidinin, malvidin showed good results targets three parasite species negative potential toxicities. echioidinin ligands generated interactions in active center at pH 2.0 conditions by MM-GBSA FEP methods. Conclusions: This work suggests activity of thus can be further vitro vivo experimentally validated.

Язык: Английский

Процитировано

9
Field-Deployable Treatments For Leishmaniasis: Intrinsic Challenges, Recent Developments and Next Steps DOI Creative Commons
Thalia Pacheco‐Fernández,

Hannah L. Markle,

Chaitenya Verma

и другие.

Research and Reports in Tropical Medicine, Год журнала: 2023, Номер Volume 14, С. 61 - 85

Опубликована: Июль 1, 2023

Leishmaniasis is a neglected tropical disease endemic primarily to low-and middle-income countries, for which there has been inadequate development of affordable, safe, and efficacious therapies.Clinical manifestations leishmaniasis range from selfhealing skin lesions lethal visceral infection with chances relapse.Although treatments are available, secondary effects limit their use outside the clinic negatively impact quality life patients in areas.Other non-medicinal treatments, such as thermotherapies, limited cutaneous but not infection.Recent studies shed light mechanisms through Leishmania can persist by hiding cellular safe havens, even after chemotherapies.This review focuses on exploring niches that parasites may be leveraging within host.Also, cellular, metabolic, molecular implications how those could targeted therapeutic purposes discussed.Other therapies, developed against cancer or manipulation ferroptosis pathway, proposed possible due action.In particular, target hematopoietic stem cells monocytes, have recently found necessary components sustain provide niche discussed this potential field-deployable leishmaniasis.

Язык: Английский

Процитировано

9
Molecular interaction assays in silico of crotapotin from Crotalus durissus terrificus against the molecular target trypanothione reductase from Leishmania braziliensis DOI Creative Commons
Jamile Mariano Macedo, M. F. V. Souza,

Anderson Maciel de Lima

и другие.

˜The œJournal of venomous animals and toxins including tropical diseases, Год журнала: 2025, Номер 31

Опубликована: Янв. 1, 2025

Abstract Background: Leishmaniasis is a neglected disease that mainly affects impoverished populations and receives limited attention from governments research institutions. Current treatments are based on antimonial therapies, which present high toxicity cause significant side effects, such as cardiotoxicity hepatotoxicity. This study proposes using crotapotin, isolated Crotalus durissus terrificus venom, potential inhibitor of the enzyme trypanothione reductase Leishmania braziliensis (LbTR). Methods: In silico assays were conducted to evaluate interaction crotapotin with LbTR molecular docking dynamics techniques. Recombinant was expressed in E. coli, its enzymatic activity confirmed. The inhibitory action then tested assays. Results: stability these interactions confirmed over 200 ns simulations, clustering analysis GROMACS method revealing total 12 distinct clusters. five most representative clusters showed low RMSD values, indicating structural LbTR-crotapotin complex. particular, cluster 1, 3,398 frames an average 0.189 nm centroid, suggests dominant stable conformation Additional maintained values between 0.173 0.193 nm, further reinforcing robustness complex under physiological conditions. expression successful, yielding 4.8 mg/L purity, verified by SDS-PAGE. assays, partially inhibited activity, IC50 223.4 μM. Conclusion: findings suggest structured LbTR, fluctuation, although inhibition observed vitro moderate. These results indicate promising basis for developing specific inhibitors, contributing bioprospecting new antiparasitic agents.

Язык: Английский

Процитировано

0