Melinda Gomes Victor

BHT-functionalized thiazolidin-4-ones were synthesized via multicomponent strategies, with N-3 substitution influencing antioxidant activity. Compounds 4a, 4b, and 4d showed consistent radical-scavenging and oxidative stress protection.

Infections caused by the protozoan Trichomonas gallinae affect birds worldwide and represent a significant health concern in poultry production and wild bird populations. Current treatment relies primarily on the use of 5-nitroimidazoles, such as metronidazole. However, the emergence of resistant isolates and the lack of safe therapeutic alternatives have driven the search for new trichomonacidal agents. In this study, the antiparasitic activity of synthetic 1,3-thiazolidin-4-one derivatives (10a-e, 4a-g and 7h) against T. gallinae has been investigated. The compounds were obtained via a multicomponent reaction and evaluated in vitro and in silico in parasite trophozoites. Among the derivatives tested, compounds 10a, 10b, 10d, 4f, and 7h demonstrated high trichomonacidal activity in the screening assay (>90%), along with low IC₅₀ values, and no evidence of cytotoxicity in VERO CCL-81 cells. Based on these results, growth curve assays were subsequently performed, in which compounds 4f and 10b stood out, completely eliminating trophozoites within 24 h at concentrations of 125 and 250 μg/mL, respectively. Molecular docking analyses revealed that the most active compounds exhibit high binding affinity toward key enzymes involved in T. gallinae energy metabolism, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Fe-hydrogenase (FeH), and TATA-box binding protein (TBP). These interactions suggest a potential mechanism of action related to the disruption of essential metabolic and transcriptional pathways in the parasite. Our findings demonstrate that heterocyclic compounds derived from 1,3-thiazolidin-4-ones exhibit antiparasitic activity and represent promising prototypes for the development of new therapeutic agents against T. gallinae.

Background: Infections caused by the protozoan Trichomonas vaginalis affect millions of people worldwide and are responsible for one of the most common sexually transmitted diseases. Despite the efficacy of 5-nitroimidazoles like metronidazole, concerns regarding widespread resistance and the absence of viable alternatives for specific patient populations necessitate the development of structurally diverse pharmacological agents. In this study, we investigated the antiparasitic activity of 1,3-thiazolidin-4-one derivatives against T. vaginalis. Methods: Thiazolidines were synthesized via multicomponent reaction (MCR) using one-pot methodology and tested in vitro against the parasite and mammalian cell lines. Results: Seventy percent of the compounds showed more than 80% antiparasitic activity at 100 μM, with compounds 4a, 4b, and 4f exhibiting IC₅₀ ≤ 20 µM. None of the molecules exhibited cytotoxic against Vero CCL-81 and HeLa cells. Evaluation of the structure–activity relationship (SAR) indicates that the substituent at the nitrogen position of the heterocycle may be involved in the antiparasitic effect of these compounds. In silico studies also revealed that the three compounds possess adequate oral bioavailability and do not present mutagenic, tumorigenic or irritating risks. Finally, molecular docking predicted strong interactions of compounds 4a, 4b, and 4f with T. vaginalis enzymes lactate dehydrogenase and purine nucleoside phosphorylase; compound 4f also interacted with methionine Ƴ-lyase. Conclusions: These preliminary results suggest that 1,3-thiazolidin-4-ones are promising scaffolds for developing new trichomonacidal agents.

Alzheimer’s Disease (AD) is characterized by memory decline, dysregulation in cholinergic and purinergic signaling, neuroinflammation, and oxidative stress. Current treatments are limited, highlighting the need for new compounds to prevent or delay AD progression. Thiazolidinones have emerged as promising candidates due to their antioxidant, anti-inflammatory, and anticholinesterase properties. The aim of this study was to evaluate the effects of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) in a rat model of scopolamine-induced memory deficits. Male rats were divided into groups: I - Control, II - Scopolamine (SCO) (1 mg/kg), III - SCO and DS27 (5 mg/kg), IV - SCO and DS27 (10 mg/kg), V - SCO and donepezil (5 mg/kg). The animals were treated orally with DS27 or donepezil for seven days. On the 8th day, they underwent the open field test and inhibitory avoidance training, followed by intraperitoneal administration SCO. Twenty-four hours later, an inhibitory avoidance test was conducted. Acetylcholinesterase (AChE) activity, oxidative stress, and inflammatory and purinergic parameters were analyzed in the cerebral cortex, hippocampus, cerebrospinal fluid, serum, lymphocytes, and liver. DS27 prevented memory deficits, alterations in AChE activity, and oxidative damage induced by SCO in brain structures. Additionally, DS27 prevented SCO-induced decrease in IL-10 levels, and increase in IL-6, and TNF-α expression in the cerebral cortex, and normalized ATP and ADP hydrolysis in cerebrospinal fluid and lymphocytes. DS27 did not induce oxidative stress in the liver or alter serum biochemical parameters. These findings suggest that DS27 has significant neuroprotective properties and could be a promising alternative for treating neurodegenerative diseases like AD. Graphical Abstract