In vitro and in silico trichomonacidal activity of 2,8-bis(trifluoromethyl) quinoline analogs against Trichomonas vaginalis

Alves, Mirna Samara Dié; Sena-Lopes, Ângela; Neves, Raquel Nascimento das; Casaril, Angela Maria; Domingues, Micaela; Birmann, Paloma T.; Silva, Emerson Teixeira da; Souza, Marcus V. N. de; Savegnago, Lucielli; Borsuk, Sibele

doi:10.1007/s00436-022-07598-1

Cited by 3 publications

(2 citation statements)

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“…However, with effective concentrations of 50 and 100 µM [25]. The other compounds are 2,8-bis(trifluoromethyl) quinoline analogs (QDA-1 and QDA-2) with an IC 50 of 113.8 µM [26] and N-acylhydrazone derivatives [27]; two of them had IC 50 values of 1.69 µM and 1.98 µM. These last compounds, as well as the O 2 N-BZM7 and O 2 N-BZM9 compounds proposed in this study, are promising antiparasitic compounds, since our results generally demonstrate the potential of O 2 N-BZM7 and O 2 N-BZM9 to affect both the enzymatic activity of TvG6PD::6PGL and the viability of T. vaginalis trophozoites, establishing a basis upon which to propose O 2 N-BZM7 and O 2 N-BZM9 as possible antitrichomonal and antigiardial drugs.…”

Section: In Vitro Assays Over T Vaginalis Trophozoitesmentioning

confidence: 99%

Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents against Giardia lamblia and Trichomonas vaginalis

et al. 2022

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Protozoan parasites, such as Giardia lamblia and Trichomonas vaginalis, cause the most prevalent infections in humans in developing countries and provoke significant morbidity and mortality in endemic countries. Despite its side-effects, metronidazole is still the drug of choice as a giardiacidal and trichomonacidal tissue-active agent. However, the emergence of metronidazole resistance and its evolved strategies of parasites to evade innate host defenses have hindered the identification and development of new therapeutic strategies against these parasites. Here, we tested five synthesized benzimidazole derivatives as possible drugs for treating giardiasis and trichomoniasis, probing the bifunctional enzyme glucose 6-phosphate dehydrogenase::6-phosphogluconolactone from G. lamblia (GlG6PD::6PGL) and T. vaginalis (TvG6PD::6PGL) as a drug target. The investigated benzimidazole derivatives were H-B2M1, H-B2M2, H2N-BZM6, O2N-BZM7, and O2N-BZM9. The recombinant enzymes were used in inhibition assays, and in silico computational predictions and spectroscopic studies were applied to follow the structural alteration of the enzymes and identify the possible mechanism of inhibition. We identified two potent benzimidazole compounds (O2N-BZM7 and O2N-BZM9), which are capable of inhibiting both protozoan G6PD::6PGL enzymes and in vitro assays with these parasites, showing that these compounds also affect their viability. These results demonstrate that other therapeutic targets of the compounds are the enzymes GlG6PD::6PGL and TvG6PD::6PGL, which contribute to their antiparasitic effect and their possible use in antigiardial and trichomonacidal therapies.

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Section: In Vitro Assays Over T Vaginalis Trophozoitesmentioning

confidence: 99%

Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents against Giardia lamblia and Trichomonas vaginalis

et al. 2022

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“…[23][24][25] They possess antimalarial, 26 antibacterial, 27 antiprotozoal, 28 antiproliferative, 29 antihypertensive, 30 and anti-HIV properties. 31 In addition, many clinical drugs contain the quinoline moiety (Fig. 2).…”

Section: Introductionmentioning

confidence: 99%