TY - JOUR
T1 - Kinetic and Molecular Docking Studies to Determine the Effect of Inhibitors on the Activity and Structure of Fused G6PD::6PGL Protein from Trichomonas vaginalis
AU - Martínez-Rosas, Víctor
AU - Hernández-Ochoa, Beatriz
AU - Navarrete-Vázquez, Gabriel
AU - Martínez-Conde, Carlos
AU - Gómez-Chávez, Fernando
AU - Morales-Luna, Laura
AU - González-Valdez, Abigail
AU - Arreguin-Espinosa, Roberto
AU - Enríquez-Flores, Sergio
AU - de la Cruz, Verónica Pérez
AU - Aguayo-Ortiz, Rodrigo
AU - Wong-Baeza, Carlos
AU - Baeza-Ramírez, Isabel
AU - Gómez-Manzo, Saúl
N1 - Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant Trichomonas vaginalis (T. vaginalis), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused T. vaginalis G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite’s energy production. We found four compounds: JMM-3, CNZ-3, CNZ-17, and MCC-7, which inhibited the TvG6PD::6PGL protein by more than 50%. Furthermore, we determined the IC50, the inactivation constants, and the type of inhibition. Our results showed that these inhibitors induced catalytic function loss of the TvG6PD::6PGL enzyme by altering its secondary and tertiary structures. Finally, molecular docking was performed for the best inhibitors, JMM-3 and MCC-7. All our findings demonstrate the potential role of these selected hit compounds as TvG6PD::6PGL enzyme selective inhibitors.
AB - Trichomoniasis is a sexually transmitted disease with a high incidence worldwide, affecting 270 million people. Despite the existence of a catalog of available drugs to combat this infection, their extensive use promotes the appearance of resistant Trichomonas vaginalis (T. vaginalis), and some side effects in treated people, which are reasons why it is necessary to find new alternatives to combat this infection. In this study, we investigated the impact of an in-house library comprising 55 compounds on the activity of the fused T. vaginalis G6PD::6PGL (TvG6PD::6PGL) protein, a protein mediating the first reaction step of the pentose phosphate pathway (PPP), a crucial pathway involved in the parasite’s energy production. We found four compounds: JMM-3, CNZ-3, CNZ-17, and MCC-7, which inhibited the TvG6PD::6PGL protein by more than 50%. Furthermore, we determined the IC50, the inactivation constants, and the type of inhibition. Our results showed that these inhibitors induced catalytic function loss of the TvG6PD::6PGL enzyme by altering its secondary and tertiary structures. Finally, molecular docking was performed for the best inhibitors, JMM-3 and MCC-7. All our findings demonstrate the potential role of these selected hit compounds as TvG6PD::6PGL enzyme selective inhibitors.
KW - Alterations on 3D
KW - Docking studies
KW - Fused G6PD::6PGL
KW - Inhibitors
KW - Trichomoniasis
UR - http://www.scopus.com/inward/record.url?scp=85124617743&partnerID=8YFLogxK
U2 - 10.3390/molecules27041174
DO - 10.3390/molecules27041174
M3 - Artículo
C2 - 35208965
AN - SCOPUS:85124617743
SN - 1420-3049
VL - 27
JO - Molecules
JF - Molecules
IS - 4
M1 - 1174
ER -