TY - JOUR
T1 - Antiparasitic activity of furanyl N-acylhydrazone derivatives against Trichomonas vaginalis
T2 - In vitro and in silico analyses
AU - Alves, Mirna Samara Dié
AU - Das Neves, Raquel Nascimento
AU - Sena-Lopes, Ângela
AU - Domingues, Micaela
AU - Casaril, Angela Maria
AU - Segatto, Natália Vieira
AU - Nogueira, Thaís Cristina Mendonça
AU - De Souza, Marcus Vinicius Nora
AU - Savegnago, Lucielli
AU - Seixas, Fabiana Kömmling
AU - Collares, Tiago
AU - Borsuk, Sibele
N1 - Publisher Copyright:
© 2020 The Author(s).
PY - 2020/2/11
Y1 - 2020/2/11
N2 - Background: Trichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexually transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with serious complications such as HIV transmission and acquisition, pelvic inflammatory disease and preterm birth. Although trichomoniasis is treated with oral metronidazole (MTZ), the number of strains resistant to this drug is increasing (2.5-9.6%), leading to treatment failure. Therefore, there is an urgent need to find alternative drugs to combat this disease. Methods: Herein, we report the in vitro and in silico analysis of 12 furanyl N-acylhydrazone derivatives (PFUR 4, a-k) against Trichomonas vaginalis. Trichomonas vaginalis ATCC 30236 isolate was treated with seven concentrations of these compounds to determine the minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50). In addition, compounds that displayed anti-T. vaginalis activity were analyzed using thiobarbituric acid reactive substances (TBARS) assay and molecular docking. Cytotoxicity analysis was also performed in CHO-K1 cells. Results: The compounds PFUR 4a and 4b, at 6.25 μM, induced complete parasite death after 24 h of exposure with IC50 of 1.69 μM and 1.98 μM, respectively. The results showed that lipid peroxidation is not involved in parasite death. Molecular docking studies predicted strong interactions of PFUR 4a and 4b with T. vaginalis enzymes, purine nucleoside phosphorylase, and lactate dehydrogenase, while only PFUR 4b interacted in silico with thioredoxin reductase and methionine gamma-lyase. PFUR 4a and 4b led to a growth inhibition (< 20%) in CHO-K1 cells that was comparable to the drug of choice, with a promising selectivity index (> 7.4). Conclusions: Our results showed that PFUR 4a and 4b are promising molecules that can be used for the development of new trichomonacidal agents for T. vaginalis.[Figure not available: see fulltext.]
AB - Background: Trichomonas vaginalis is the causative agent of trichomoniasis, which is one of the most common sexually transmitted diseases worldwide. Trichomoniasis has a high incidence and prevalence and is associated with serious complications such as HIV transmission and acquisition, pelvic inflammatory disease and preterm birth. Although trichomoniasis is treated with oral metronidazole (MTZ), the number of strains resistant to this drug is increasing (2.5-9.6%), leading to treatment failure. Therefore, there is an urgent need to find alternative drugs to combat this disease. Methods: Herein, we report the in vitro and in silico analysis of 12 furanyl N-acylhydrazone derivatives (PFUR 4, a-k) against Trichomonas vaginalis. Trichomonas vaginalis ATCC 30236 isolate was treated with seven concentrations of these compounds to determine the minimum inhibitory concentration (MIC) and 50% inhibitory concentration (IC50). In addition, compounds that displayed anti-T. vaginalis activity were analyzed using thiobarbituric acid reactive substances (TBARS) assay and molecular docking. Cytotoxicity analysis was also performed in CHO-K1 cells. Results: The compounds PFUR 4a and 4b, at 6.25 μM, induced complete parasite death after 24 h of exposure with IC50 of 1.69 μM and 1.98 μM, respectively. The results showed that lipid peroxidation is not involved in parasite death. Molecular docking studies predicted strong interactions of PFUR 4a and 4b with T. vaginalis enzymes, purine nucleoside phosphorylase, and lactate dehydrogenase, while only PFUR 4b interacted in silico with thioredoxin reductase and methionine gamma-lyase. PFUR 4a and 4b led to a growth inhibition (< 20%) in CHO-K1 cells that was comparable to the drug of choice, with a promising selectivity index (> 7.4). Conclusions: Our results showed that PFUR 4a and 4b are promising molecules that can be used for the development of new trichomonacidal agents for T. vaginalis.[Figure not available: see fulltext.]
KW - Antiparasitic
KW - Lipid peroxidation
KW - Molecular docking
KW - Trichomonacidal
KW - Trichomoniasis
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U2 - 10.1186/s13071-020-3923-8
DO - 10.1186/s13071-020-3923-8
M3 - Article
C2 - 32046788
AN - SCOPUS:85079337974
SN - 1756-3305
VL - 13
JO - Parasites and Vectors
JF - Parasites and Vectors
IS - 1
M1 - 59
ER -