Effect of Thiazolidin-4-one Against Lipopolysaccharide-Induced Oxidative Damage, and Alterations in Adenine Nucleotide Hydrolysis and Acetylcholinesterase Activity in Cultured Astrocytes.

Astrocytes play multiple important roles in brain physiology. However, depending on the stimuli, astrocytes may exacerbate inflammatory reactions, contributing to the development and progression of neurological diseases. Therefore, therapies targeting astrocytes represent a promising area for the development of new brain drugs. Thiazolidinones are heterocyclic compounds that have a sulfur and nitrogen atom and a carbonyl group in the ring and represent a class of compounds of great scientific interest due to their pharmacological properties. The aim of this study was to investigate the effect of 3-(3-(diethylamino)propyl)-2-(4-(methylthio)phenyl)thiazolidin-4-one (DS27) on cell proliferation and morphology, oxidative stress parameters, activity of the enzymes ectonucleotidases and acetylcholinesterase (AChE) and interleukin 6 (IL-6) levels in primary astrocyte cultures treated with lipopolysaccharide (LPS), to model neuroinflammation. The astrocyte culture was exposed to LPS (10 µg/ml) for 3 h and subsequently treated with compound DS27 for 24 and 48 h (concentrations ranging to 10-100 µM). LPS induced an increase in astrocyte proliferation, AChE activity, IL-6 levels, oxidative damage, ATP and ADP and a reduction in AMP hydrolysis in rat primary astrocyte cultures. DS27 treatment was effective in reversing these alterations induced by LPS. Our findings demonstrated that DS27 is able to modulate cholinergic and purinergic signaling, redox status, and the levels of pro-inflammatory cytokines in LPS-induced astrocyte damage. These glioprotective effects of DS27 may be very important for improving neuroinflammation, which is associated with many brain diseases.

Therapeutic potential of blackberry extract in the preventing memory deficits and neurochemical alterations in the cerebral cortex, hippocampus and cerebellum of a rat model with amnesia.

The blackberry (Rubus sp.) is a popular fruit that has a high concentration of phenolic compounds. Pharmacological investigations have demonstrated the important biological activities of the blackberry extract, such as neuroprotective actions. This study aimed to evaluate the effects of blackberry extract on memory and neurochemical parameters in rats subjected to scopolamine (SCO)-induced amnesia. Male rats were divided into five groups: I, control (saline); II, SCO; III, SCO + Rubus sp. (100 mg/kg); IV, SCO + Rubus sp. (200 mg/kg); and V, SCO + donepezil (5 mg/kg). Blackberry extract and donepezil were orally administered for 10 days. On day 11, group I received saline, and groups II, III, IV, and V received SCO (1 mg/kg) intraperitoneally after object recognition behavioral training. Twenty-four hours after the training session, animals were subjected to an object recognition test. Finally, the animals were euthanized, and the cerebral cortex, hippocampus, and cerebellum were collected to evaluate the oxidative stress and acetylcholinesterase (AChE) activity. Rubus sp. extract prevented memory impairment induced by SCO in a manner similar to that of donepezil. Additionally, Rubus sp. extract and donepezil prevented the increase in AChE activity induced by SCO in all the evaluated brain structures. SCO induced oxidative damage in the cerebral cortex, hippocampus, and cerebellum, which was prevented by Rubus sp. and donepezil. Our results suggest that the antioxidant and anticholinesterase activities of Rubus sp. are associated with memory improvement; hence, it can potentially be used for the treatment of neurodegenerative diseases.

Thiazolidine-2,4-dione derivative exhibits antitumoral effect and reverts behavioral and metabolic changes in a model of glioblastoma.

The aim of the present study was to evaluate the anti-glioma activity of 3-(4-fluorobenzyl)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione (AV23) in a preclinical model of glioblastoma, as well as behavioral parameters and toxicological profile. The implantation of C6 cells in the left striatum of male Wistar rats was performed by stereotaxic surgery. After recovery, animals were treated with vehicle (canola oil) or AV23 (10 mg/kg/day) intragastrically for 15 days. It was found that AV23 reduced tumor volume by 90%. Serum biochemical parameters such as triglycerides, cholesterol, HDL-cholesterol, LDL-cholesterol, albumin, aspartate aminotransferase, urea, creatinine and total proteins were not changed; however, there was a slight increase in alanine aminotransferase. The compound AV23 reverted the hypoglycemia and the reduction in body weight caused by glioblastoma. Additionally, AV23 was able to revert the reduction of locomotion caused by the tumor implantation. Therefore, the compound AV23 can be considered a promising candidate in the treatment of glioblastoma.

Multitarget Effect of 2-(4-(Methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one in a Scopolamine-Induced Amnesic Rat Model.

Cholinergic system dysfunction, oxidative damage, and alterations in ion pump activity have been associated with memory loss and cognitive deficits in Alzheimer's disease. 1,3-thiazolidin-4-ones have emerged as a class of compounds with potential therapeutic effects due to their potent anticholinesterase activity. Accordingly, this study investigated the effect of the 2-(4-(methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one (DS12) compound on memory, cholinergic and oxidative stress parameters, ion pump activity, and serum biochemical markers in a scopolamine-induced memory deficit model. Male Wistar rats were divided into four groups: I-Control; II-Scopolamine; III-DS12 (5 mg/kg) + scopolamine; and IV-DS12 (10 mg/kg) + scopolamine. The animals from groups III and IV received DS12 diluted in canola oil and administered for 7 days by gavage. On the last day of treatment, scopolamine (1 mg/kg) was administered intraperitoneally (i.p.) 30 min after training in an inhibitory avoidance apparatus. Twenty-four hours after scopolamine administration, the animals were subjected to an inhibitory avoidance test and were thereafter euthanized. Scopolamine induced memory deficits, increased acetylcholinesterase activity and oxidative damage, and decreased Na+/K+-ATPase activity in cerebral cortex and hippocampus. Pretreatment with DS12 prevented these brain alterations. Scopolamine also induced an increase in acetylcholinesterase activity in lymphocytes and whereas butyrylcholinesterase in serum and treatment with DS12 prevented these changes. In animals treated with DS12, no changes were observed in renal and hepatic parameters when compared to the control group. In conclusion, DS12 emerged as an important multitarget compound capable of preventing neurochemical changes associated with memory deficits.

Three -(pyridin-2-yl)-2-(pyridin-2-ylimino)thiazolidin-4-one as a novel inhibitor of cerebral MAO-B activity with antioxidant properties and low toxicity potential.

Some brain diseases are associated with oxidative stress and altered monoamine oxidase (MAO) activity. The objective of this study was to evaluate the antioxidant and neuroprotective actions through MAO inhibition of 3-(pyridin-2-yl)-2-(pyridine-2-ylimino) thiazolidin-4-one (PPIT, a synthetic molecule containing a thiazolidinone nucleus), as well as its effects on toxicity parameters in Swiss female mice. Five in vitro assays were carried out to verify the PPIT antioxidant capacity: protein carbonylation (PC), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picryl-hydrazil (DPPH), ferric ion (Fe3+ ) reducing antioxidant power (FRAP), and superoxide dismutase (SOD)-like activity. The results showed that PPIT reduced the level of PC in the homogenate of the brain. This compound did not demonstrate SOD mimetic activity, but it acted as a free radical scavenger (ABTS and DPPH) and exhibited reducing activity in the FRAP assay. In addition, the effects of PPIT on cerebral MAO activity (MAO-A and B isoforms) were investigated in vitro. Our data revealed inhibition of the MAO-B activity by PPIT with no effects on MAO-A. Lastly, an acute oral toxicity test was conducted in mice. No changes in food intake, body weight, and biochemical markers of kidney and liver damage were detected in mice treated with a high dose of PPIT (300 mg/kg). In conclusion, the present study demonstrated that PPIT exhibits antioxidant activity and selectively inhibits the MAO-B isoform without causing apparent toxicity. These findings suggest PPIT as a potential therapeutic candidate to be tested in preclinical models of brain diseases involving perturbations of MAO-B activity and redox status.

In Vitro Effects of 2-{4-[Methylthio(methylsulfonyl)]phenyl}-3-substitutedthiazolidin-4-ones on the Acetylcholinesterase Activity in Rat Brain and Lymphocytes: Isoform Selectivity, Kinetic Analysis, and Molecular Docking.

This work evaluated the in vitro effect of thiazolidin-4-ones on the activity of AChE (total and isoforms) isolated from the cerebral cortex, hippocampus, and lymphocytes. Kinetic parameters were evaluated and molecular docking was performed. Our results showed that thiazolidinones derived from 4-(methylthio)benzaldehyde (1) and from 4-(methylsulfonyl)benzaldehyde (2) were capable of inhibiting the AChE activity in vitro. Three compounds, two with a propylpiperidine (1b and 2b) moiety and one with a 3-(diethylamino)propyl (1c) moiety showed IC50 values of 13.81 µM, and 3.13 µM (1b), 55.36 µM and 44.33 µM (1c) for cerebral cortex and hippocampus, respectively, and 3.11 µM for both (2b). Enzyme kinetics revealed that the type of AChE inhibition was mixed. Compound 1b inhibited the G1 and G4 AChE isoforms, while compounds 1c and 2b selectively inhibited the G4 isoform. Molecular docking showed a possible three-dimensional fit into the enzyme. Our findings showed that these thiazolidin-4-ones, especially those containing the propylpiperidine core, have a potential cholinesterase inhibitory activity and can be considered good candidates for future Alzheimer's therapy.

Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors.

The present study describes the synthesis of a novel series of thiazolidin-4-one and thiazinan-4-one using 1-(2-aminoethyl)pyrrolidine as amine precursor. All compounds were synthesised by one-pot three component cyclocondensation reaction from the amine, a substituted benzaldehyde and a mercaptocarboxylic acid. The compounds were obtained in moderate to good yields and were identified and characterised by 1H, 13 C, 2 D NMR and GC/MS techniques. The compounds also were screened for their in vitro acetylcholinesterase (AChE) activity in hippocampus and cerebral cortex on Wistar rats. The six most potent compounds have been investigated for their cytotoxicity by cell viability assay of astrocyte primary culture, an important cell of central nervous system. We highlighted two compounds (6a and 6k) that had the lowest IC50 in hippocampus (5.20 and 4.46 µM) and cerebral cortex (7.40 and 6.83 µM). These preliminary and important results could be considered a starting point for the development of new AChE inhibitory agents.

2-(2-Methoxyphenyl)-3-((Piperidin-1-yl)ethyl)thiazolidin-4-One-Loaded Polymeric Nanocapsules: In Vitro Antiglioma Activity and In Vivo Toxicity Evaluation.

Among gliomas types, glioblastoma is considered the most malignant and the worst form of primary brain tumor. It is characterized by high infiltration rate and great angiogenic capacity. The presence of an inflammatory microenvironment contributes to chemo/radioresistance, resulting in poor prognosis for patients. Recent data show that thiazolidinones have a wide range of pharmacological properties, including anti-inflammatory and antiglioma activities. Nanocapsules of biodegradable polymers become an alternative to cancer treatment since they provide targeted drug delivery and could overcome blood-brain barrier. Therefore, here we investigated the in vitro antiglioma activity and the potential in vivo toxicity of 2- (2-methoxyphenyl) -3- ((piperidin-1-yl) ethyl) thiazolidin-4-one-loaded polymeric nanocapsules (4L-N). Nanocapsules were prepared and characterized in terms of particle size, polydispersity index, zeta potential, pH, molecule content and encapsulation efficiency. Treatment with 4L-N selectively decreased human U138MG and rat C6 cell lines viability and proliferation, being even more efficient than the free-form molecule (4L). In addition, 4L-N did not promote toxicity to primary astrocytes. We further demonstrated that the treatment with sub-therapeutic dose of 4L-N did not alter weight, neither resulted in mortality, toxicity or peripheral damage to Wistar rats. Finally, 4L as well as 4L-N did not alter makers of oxidative damage, such as TBARS levels and total sulfhydryl content, and did not change antioxidant enzymes SOD and CAT activity in liver and brain of treated rats. Taken together, these data indicate that the nanoencapsulation of 4L has potentiated its antiglioma effect and does not cause in vivo toxicity.

Synthesis and biological evaluation of benzothiazin-4-ones: a possible new class of acetylcholinesterase inhibitors.

A series of nineteen benzothiazin-4-ones from N-(3-aminopropyl) piperidine, 4-(2-aminoethyl)morpholine or 1-(2-aminoethyl)piperidine, aliphatic or aromatic aldehyde and thiosalicylic acid, were synthesized in good yields by multicomponent one-pot reactions. The solvent was toluene and this efficient procedure afforded the desired heterocycles in 5 h. Identification and characterization were achieved by NMR and GC-MS techniques. In vitro AChE activities of all compounds were evaluated in cerebral cortex and hippocampus of rats and in general, the results in cortex were more promising than hippocampus. The benzothiazinone 5Bd showed the best AChE inhibition activity IC50 8.48 µM (cortex) and IC50 39.80 µM (hippocampus). The cytotoxicity of seven compounds in MCR-5 human fibroblast cell by SRB test in 24 h were evaluated and 5Bd suggest preliminary safety, showing no cytotoxicity at 100 µM. Finally, these important findings could be a starting point for the development of new AChE inhibitors agents and will provide the basis for new studies.

Ovicidal in vitro activity of 2-aryl-3-(2-morpholinoethyl)thiazolidin-4-ones and 2-aryl-3-(3-morpholinopropyl)thiazolidin-4-ones against Fasciola hepatica (Linnaeus, 1758).

Although there is a variety of biological activity reports regarding compounds derived from thiazolidin-4-ones, no data related to ovicidal activity against trematodes, particularly Fasciola hepatica are available. Since there are reports about anthelmintic resistance in F. hepatica, new drugs are required. Thus, this study evaluated ovicidal action in vitro against F. hepatica eggs in two systematic series of thiazolidin-4-ones: 2-aryl-3-(2-morpholinoethyl)thiazolidin-4-ones (1a-h) and 2-aryl-3-(3-morpholinopropyl)thiazolidin-4-ones (2a-h) at different concentrations (20, 2, 0.2, 0.02 and 0.002 µg/ml). The egg hatch assay (EHA) was used to evaluate the ovicidal action property of such compounds. In addition, potential negative effects of the compounds on metabolic activity of bovine kidney (MDBK) cells were evaluated by determining mitochondrial dehydrogenase activity. The eggs used in the EHA were obtained from parasites removed from the liver of cattle, which were discarded by slaugh after sanitary inspection. The results of EHA showed that compounds 2a-h exhibited ovicidal activity, especially compounds 2b which showed 90% ovicidal activity and viability of 93% MDBK cells at the concentration of 2 µg/ml; and 2e with 96-99% ovicidal activity at 0.2 µg/ml, 0.02 µg/ml and 0.002 µg/ml. The results show the potential of compound 2b to continue the studies in the production of new compounds with anthelmintic action.

Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms.

BACKGROUND: Primaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes. RESULTS: All primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro. Sera from mice pretreated with the test compounds thus assumed to have drug metabolites, caused no in vitro haemolysis of human erythrocytes, whereas sera from mice pretreated with primaquine did cause haemolysis. The ability of the PQ-TZs to block malaria transmission was evaluated based on the oocyst production and percentage of mosquitoes infected after a blood meal in drug pre-treated animals with experimental malaria caused by either Plasmodium gallinaceum or Plasmodium berghei; four and five PQ-TZs significantly inhibited sporogony in avian and in rodent malaria, respectively. Selected PQ-TZs were tested for their inhibitory activity on P. berghei liver stage development, in mice and in vitro, one compound (4m) caused a 3-day delay in the malaria pre-patent period. CONCLUSIONS: The compound 4m was the most promising, blocking malaria transmissions and reducing the number of exoerythrocytic forms of P. berghei (EEFs) in hepatoma cells in vitro and in mice in vivo. The same compound also caused a 3-day delay in the malaria pre-patent period.

(7-Chloroquinolin-4-yl)arylhydrazones: Candida albicans enzymatic repression and cytotoxicity evaluation, Part 2.

OBJECTIVE: This work describes the anti-enzymatic activity of (7-chloroquinolin-4-yl)arylhydrazones against Candida albicans and examines their cytotoxicity. MATERIAL AND METHODS: Ten C. albicans strains [nine isolates and one azole-resistant standard strain (ATCC 62342)] were used to assess the anti-enzymatic activity. Fifteen compounds at sub-antifungal concentrations ranging from 12.5 to 100 µg/ml were assessed after a 30-min exposure. The strains were seeded onto petri dishes with selective agar media for aspartyl proteases (Saps) and phospholipases (PLs). Enzymatic inhibition was measured by the reduction of the precipitation zone (Pz) against untreated strains (positive control). A colorimetric MTT assay was used with 3T3/NIH mouse fibroblasts to evaluate cytotoxicity. Cells were exposed to 15 compounds in concentrations from 6.25 to 100 µg/ml for 24 and 48 h. RESULTS: Four hydrazones showed enzymatic repression values over 40% to Pl and three over 20% to Saps. The cell viability was over 50% at hydrazone concentrations of 25-100 µg/ml. CONCLUSION: These results revealed that select (7-chloroquinolin-4-yl)arylhydrazones may be potential antifungal agents for the control of C. albicans infections.

Synthesis and antioxidant activity of 3-(Pyridin-2-ylmethyl)-1,3-thiazinan(thiazolidin)-4-ones.

The antioxidant properties of two series of thiazolidinones and thiazinanones were reported. The novel six-membered thiazinanones were synthesized from the efficient multicomponent reaction of 2-picolylamine (2-aminomethylpyridine), arenaldehydes, and the 3-mercaptopropionic acid in moderate to excellent yields. These novel compounds were fully identified and characterized by NMR and GC-MS techniques. In vitro antioxidant activities of all compounds were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) tests. The antioxidant assays of thiobarbituric acid reactive species and total thiol content levels in the cerebral cortex and liver of rats were also performed. Thiazinanone 5a showed the best radical scavenging activity in DPPH and ABTS tests, as well as reduced lipid peroxidation and increased total thiol group in biological systems. Altogether, the results may be considered a good starting point for the discovery of a new radical scavenger.

Efficient synthesis and antioxidant evaluation of 2-aryl-3-(pyrimidin-2-yl)-thiazolidinones.

In the present study, we reported the efficient synthesis of 11 3-(pyrimidin-2-yl)-thiazolidinones in good yields using molecular sieve as the desiccant agent. In addition, we have evaluated the antioxidant capacity of the synthesized compounds by the 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH•) and the 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS(+•) ) radicals scavenging assay. Six compounds showed antioxidant activity towards DPPH• (EC50 between 16.13 and 49.94 µg/mL) and also demonstrated excellent activity regarding ABTS(+•) (TEAC: 10.32-53.52). These results showed that compounds 3-(pyrimidin-2-yl)-thiazolidinones may be easily synthesized by a less expensive procedure and could be a good starting point to the development of new antioxidant compounds.

Thiazolidin-4-one prevents against memory deficits, increase in phosphorylated tau protein, oxidative damage and cholinergic dysfunction in Alzheimer disease model: Comparison with donepezil drug.

Alzheimer's disease (AD) is characterized mostly by memory decline. The current therapeutic arsenal for treating AD is limited, and the available drugs only produce symptomatic benefits, but do not stop disease progression. The search for effective therapeutic alternatives with multitarget actions is therefore imperative. One such a potential alternative is thiazolidin-4-one, a compound that exhibits anti-amnesic, anticholinesterase, and antioxidant activities. The aim of this study was evaluated the effects of 2-(4-(methylthio)phenyl)- 3-(3-(piperidin-1-yl)propyl) thiazolidin-4-one (DS12) on memory and neurochemical parameters in a model of AD induced by an intracerebroventricular injection of streptozotocin (STZ). Adult male rats were divided into five groups: I, control (saline); II, DS12 (10 mg/kg); III, STZ; IV, STZ + DS12 (10 mg/kg); V, STZ + donepezil (5 mg/kg). The rats were orally treated with DS12 and donepezil for a period of 20 days. Memory, acetylcholinesterase (AChE) activity, phosphorylated tau protein levels and oxidative stress were analyzed in the cerebral cortex, hippocampus, and cerebellum. Biochemical and hematological parameters were evaluated in the blood and serum. Memory impairment and the increase in AChE activity and phosphorylated tau protein level induced by STZ were prevented by DS12 and donepezil treatment. Streptozotocin induces an increase in reactive oxygen species levels and a decrease in catalase activity in the hippocampus, cerebral cortex, and cerebellum. DS12 treatment conferred protection from oxidative alterations in all brain structures. No changes were observed in serum biochemical parameters (glucose, triglycerides, cholesterol, uric acid, and urea) or hematological parameters, such as platelets, lymphocytes, hemoglobin, hematocrit, and total plasma protein. DS12 improved memory and neurochemical changes in an AD model and did not show toxic effects, suggesting the promising therapeutic potential of this compound.

Synthesis and Biological Evaluation of Novel 2-imino-4-thiazolidinones as Potential Antitumor Agents for Glioblastoma.

AIMS: The purpose of our study was to explore the molecular hybridization between 2- imino-4-thizolidione and piridinic scaffolds and its potential antitumor activity. BACKGROUND: Glioblastoma is the most aggressive glioma tumor clinically diagnosed malignant and highly recurrent primary brain tumor type. The standard of treatment for a glioblastoma is surgery, followed by radiation and chemotherapy using temozolomide. However, the chemoresistance has become the main barrier to treatment success. 2-imino-4-thiazolidinones are an important class of heterocyclic compounds that feature anticancer activity; however the antiglioblastoma activity is yet to be explored. OBJECTIVE: To synthesize and characterize a series of novel 2-imino-4-thiazolidinones and evaluate their antiglioblastoma activity. METHODS: The 2-imino-4-thiazolidinone (5a-p) was synthesized according to the literature with modifications. Compounds were identified and characterized using spectroscopic analysis and X-ray diffraction. The antitumor activity was analyzed by 3-(4,5- dimethyl)-2,5-diphenyltetrazolium bromide (MTT) assay both in primary astrocyte and glioma (C6). Apoptosis and cell cycle phase were determined by flow cytometry analysis. The expression of caspase-3/7 was measured by luminescence assay. Oxidative stress parameters as: Determination of Reactive Oxygen Species (ROS), Superoxide Dismutase (SOD) activity, Catalase (CAT) activity and total sulfhydryl content quantification were analyzed by colorimetric assays according to literature. RESULTS: Among sixteen synthesized compounds, three displayed potent antitumor activities against tested glioblastoma cell line showed IC50 values well below the standard drug temozolomide. Therefore, compounds 5a, 5l and 5p were evaluated using cell cycle and death analysis, due to potent toxicity (2.17±1.17, 6.24±0.59, 2.93±1.12µM, respectively) in C6 cell line. The mechanism of action studies demonstrated that 5a and 5l induced apoptosis significantly increase the percentage of cells in Sub-G1 phase in the absence of necrosis. Consistent with these results, caspase-3/7 assay revealed that 5l presents pro-apoptotic activity due to the significant stimulation of caspases-3/7. Moreover, 5a, 5l and 5p increased antioxidant defense and decreased reactive oxygen species (ROS) production. CONCLUSION: The compounds were synthesized with good yield and three of these presented (5a, 5l and 5p) good cytotoxicity against C6 cell line. Both affected cell cycle distribution via arresting more C6 cell line at Sub-G1 phase promoting apoptosis. Furthermore, 5a, 5l and 5p modulated redox status. These findings suggest that these compounds can be considered as promising lead molecules for further development of potential antitumor agents.

7-chloroquinolin-4-yl arylhydrazone derivatives: synthesis and antifungal activity.

Fifteen 7-chloro-4-arylhydrazonequinolines have been evaluated for their in vitro antifungal activity against eight oral fungi: Candida albicans, C. parapsilosis, C. lipolytica, C. tropicalis, C. famata, C. glabrata, Rhodutorula mucilaginosa, and R. glutinis. Several compounds exhibited minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) activities comparable with the first-line drug fluconazole. These results could be considered as an important starting point for the rational design of new antifungal agents.

3-(2H-1,3-Benzodioxol-5-ylmeth-yl)-2-(2-meth-oxy-phen-yl)-1,3-thia-zolidin-4-one.

The title mol-ecule, C(18)H(17)NO(4)S, features a 1,3-thia-zolidine ring that is twisted about the S-C(methyl-ene) bond. With reference to this ring, the 1,3-benzodioxole and benzene rings lie to either side and form dihedral angles of 69.72 (16) and 83.60 (14)°, respectively, with the central ring. Significant twisting in the mol-ecule is confirmed by the dihedral angle of 79.91 (13)° formed between the outer rings. Linear supra-molecular chains along the a-axis direction mediated by C-H⋯O inter-actions feature in the crystal packing.

N-{(2S)-3-Hy-droxy-4-[(5-methyl-1,3,4-thia-diazol-2-yl)sulfan-yl]-1-phenyl-2-but-yl}-4-methyl-benzene-sulfonamide.

The thia-diazoyl and sulfonyl-benzene rings in the title compound, C(20)H(23)N(3)O(3)S(3), are aligned to the same side of the mol-ecule, forming a twisted 'U' shape [dihedral angle = 77.6 (5)°]. The benzyl-benzene ring is orientated in the opposite direction from the mol-ecule but projects approximately along the same axis as the other rings [dihedral angle between benzene rings = 28.2 (5)°] so that, overall, the mol-ecule has a flattened shape. The hy-droxy and amine groups are almost syn which enables the formation of inter-molecular hy-droxy-OH⋯N(thia-diazo-yl) and amine-H⋯O(sulfon-yl) hydrogen bonds leading to a supra-molecular chain aligned along the a axis.

2,4-Thiazolidinedione as Precursor to the Synthesis of Compounds with Anti-glioma Activities in C6 and GL261 Cells.

BACKGROUND: Thiazolidinediones (TZDs) represent an important class of heterocyclic compounds that have versatile biological activities, including anticancer activity. Glioma is one of the most common primary brain tumors, and it is responsible for most of the deaths caused by primary brain tumors. In the present work, 2,4-thiazolidinediones were synthesized via a multicomponent microwave one-pot procedure. The cytotoxicity of compounds was analyzed in vitro using rat (C6) and mouse (GL261) glioblastoma cell lines and primary cultures of astrocytes. OBJECTIVE: This study aims to synthesize and characterize 2,4-thiazolidinediones and evaluate their antitumor activity. METHODS: TZDs were synthesized from three components: 2,4-thiazolidinedione, arene-aldehydes, and aryl chlorides. The reactions were carried out inside a microwave and monitored using thinlayer chromatography (TLC). Compounds were identified and characterized using gas chromatography coupled to mass spectrometry (CG-MS) and hydrogen (1H-NMR) and carbon nuclear magnetic resonance spectroscopy (13C-NMR). The antitumor activity was analyzed using the 3-(4,5- dimethyl)-2,5-diphenyltetrazolium bromide (MTT) reduction test, in which cell viability was verified in the primary cultures of astrocytes and in rat and mouse glioblastoma cells exposed to the synthesized compounds. The cytotoxicity of all derivatives was analyzed at the 100 µM concentration, both in astrocytes and in the mouse and rat glioblastoma cell lines. The compounds that showed the best results, 4CI and 4DI, were also tested at concentrations 25, 50, 100, 175, and 250 µM to obtain the IC50. RESULTS: Seventeen TZD derivatives were easily obtained through one-pot reactions in 40 minutes with yields ranging from 12% to 49%. All compounds were cytotoxic to both glioblastoma cell lines without being toxic to the astrocyte primary cell line at 100 µM, thus demonstrating a selective activity. Compounds 4CI and 4DI showed the best results in the C6 cells: IC50 of 28.51 µM and 54.26 µM, respectively. CONCLUSION: The compounds were not cytotoxic in astrocyte culture, demonstrating selectivity for malignant cells. Changes in both rings are important for anti-glioma activity in the cell lines tested. TZD 4CI had the best anti-glioma activity.