Vicente-Barrueco, A.; Román, Á.C.; Ruiz-Téllez, T.; Centeno, F. In Silico Research of New Therapeutics Rotenoids Derivatives against Leishmania amazonensis Infection. Biology2022, 11, 133.
Vicente-Barrueco, A.; Román, Á.C.; Ruiz-Téllez, T.; Centeno, F. In Silico Research of New Therapeutics Rotenoids Derivatives against Leishmania amazonensis Infection. Biology 2022, 11, 133.
Vicente-Barrueco, A.; Román, Á.C.; Ruiz-Téllez, T.; Centeno, F. In Silico Research of New Therapeutics Rotenoids Derivatives against Leishmania amazonensis Infection. Biology2022, 11, 133.
Vicente-Barrueco, A.; Román, Á.C.; Ruiz-Téllez, T.; Centeno, F. In Silico Research of New Therapeutics Rotenoids Derivatives against Leishmania amazonensis Infection. Biology 2022, 11, 133.
Abstract
Yearly, 1,500,000 cases of leishmaniasis are diagnosed, causing thousands of deaths. To advance in its therapy, we present an interdisciplinary protocol that unifies ethnobotanical knowledge of natural compounds and the latest bioinformatics advances to respond to an orphan disease such as leishmaniasis and specifically the one caused by Leishmania amazonensis. The use of ethnobotanical information serves as a basis for the development of new drugs, a field in which computer-aided drug design (CADD) has been a revolution. Taking this information from Amazonian communities, located in the area with the highest prevalence of this disease, a protocol has been designed to verify new leads. Moreover, a method has been developed that allows the evaluation of lead molecules, and the improvement of their affinity and specificity against therapeutic targets. Through this approach, deguelin has been identified as a good lead to treat the infection due to its potential as an ornithine decarboxylase (ODC) inhibitor, a key enzyme in Leishmania development. Using an in silico-generated combinatorial library followed by docking approaches, we have found deguelin derivatives with better affinity and specificity against ODC than the original compound, suggesting that this approach could be adapted for developing new drugs against leishmaniasis.
Keywords
Leishmania amazonensis; CADD; ODC; docking; deguelin; protein modeling.
Subject
Biology and Life Sciences, Biology and Biotechnology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
