TY - JOUR
T1 - Esters of quinoxaline-7-carboxylate-1,4-di-N-oxide as Trichomonas vaginalis triosephosphate isomerase inhibitors
AU - Palos, Isidro
AU - Moo-Puc, Rosa
AU - Vique-Sánchez, José Luis
AU - Benítez-Cardoza, Claudia G.
AU - Monge, Antonio
AU - Villalobos-Rocha, Juan Carlos
AU - Paz-Gonzalez, Alma D.
AU - Rivera, Gildardo
N1 - Publisher Copyright:
© 2021 Isidro Palos et al., published by Sciendo.
PY - 2021/9/1
Y1 - 2021/9/1
N2 - Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic ineffectiveness occurs in 5 to 20 % of the cases. Therefore, it is essential to propose new pharmacological agents against this disease. In this work, esters of quinoxaline-7-carboxylate-1,4-di-N-oxide (EQX-NO) were evaluated in in vitro assays as novel trichomonicidal agents. Additionally, an in vitro enzyme assay and molecular docking analysis against triosephosphate isomerase of Trichomonas vaginalis to confirm their mechanism of action were performed. Ethyl (compound 12) and n-propyl (compound 37) esters of quinoxaline-7-carboxy-late-1,4-di-N-oxide derivatives showed trichomonicidal activity comparable to nitazoxanide, whereas five methyl (compounds 5, 15, 19, 20 and 22), four isopropyl (compounds 28, 29, 30 and 34), three ethyl (compounds 4, 13 and 23) and one npropyl (compound 35) ester derivatives displayed activity comparable to albendazole. Compounds 6 and 20 decreased 100 % of the enzyme activity of recombinant protein triosephosphate isomerase.
AB - Trichomoniasis is a public health problem worldwide. Trichomoniasis treatment consists of the use of nitroimidazole derivatives; however, therapeutic ineffectiveness occurs in 5 to 20 % of the cases. Therefore, it is essential to propose new pharmacological agents against this disease. In this work, esters of quinoxaline-7-carboxylate-1,4-di-N-oxide (EQX-NO) were evaluated in in vitro assays as novel trichomonicidal agents. Additionally, an in vitro enzyme assay and molecular docking analysis against triosephosphate isomerase of Trichomonas vaginalis to confirm their mechanism of action were performed. Ethyl (compound 12) and n-propyl (compound 37) esters of quinoxaline-7-carboxy-late-1,4-di-N-oxide derivatives showed trichomonicidal activity comparable to nitazoxanide, whereas five methyl (compounds 5, 15, 19, 20 and 22), four isopropyl (compounds 28, 29, 30 and 34), three ethyl (compounds 4, 13 and 23) and one npropyl (compound 35) ester derivatives displayed activity comparable to albendazole. Compounds 6 and 20 decreased 100 % of the enzyme activity of recombinant protein triosephosphate isomerase.
KW - 4-di-N-oxide
KW - quinoxaline 1
KW - trichomoniasis
KW - triosephosphate isomerase inhibitor
UR - http://www.scopus.com/inward/record.url?scp=85110153731&partnerID=8YFLogxK
U2 - 10.2478/acph-2021-0032
DO - 10.2478/acph-2021-0032
M3 - Artículo
AN - SCOPUS:85110153731
SN - 1330-0075
VL - 71
SP - 485
EP - 495
JO - Acta Pharmaceutica
JF - Acta Pharmaceutica
IS - 3
ER -