Synthesis and Evaluation of New Phytotoxic Fluorinated Chalcones as Photosystem II and Seedling Growth Inhibitors.

The development of novel phytotoxic compounds has been an important aim of weed control research. In this study, we synthesized fluorinated chalcone derivatives featuring both electron-donating and electron-withdrawing groups. These compounds were evaluated both as inhibitors of the photosystem II (PSII) electron chain as well as inhibitors of the germination and seedling growth of Amaranthus plants. Chlorophyll a (Chl a) fluorescence assay was employed to evaluate their effects on PSII, while germination experiments were conducted to assess their impact on germination and seedling development. The results revealed promising herbicidal activity for (E)-3-(4-bromophenyl)-1-(4-fluorophenyl)prop-2-en-1-one (7 a) and (E)-1-(4-fluorophenyl)-3-phenylprop-2-en-1-one (7 e). Compounds 7 a and 7 e exhibited a reduction in Chl a parameters associated with performance indexes and electron transport per reaction center. This reduction suggests a decrease in PSII activity, attributed to the blockage of electron flow at the quinone pool. Molecular docking analyses of chalcone derivatives with the D1 protein of PSII revealed a stable binding conformation, wherein the carbonyl and fluorine groups interacted with Phe265 and His215 residues, respectively. Additionally, at a concentration of 100 µM, compound 7 e demonstrated pre- and post-emergent herbicidal activity, resulting in a reduction of the seed germination index, radicle and hypocotyl lengths of Amaranthus weeds.

The C-glucosyl flavone isoorientin pretreatment attenuates the methylglyoxal-induced mitochondrial dysfunction in the human neuroblastoma SH-SY5Y cells: role for the AMPK-PI3K/Akt/Nrf2/γ-GCL/GSH axis.

The reactive dicarbonyl methylglyoxal (MG) behaves as a pro-oxidant agent, causing redox dysfunction and cell death by different mechanisms in mammalian cells. MG is also a mitochondrial toxicant, impairing the oxidative phosphorylation (OXPHOS) system and leading to bioenergetics and redox collapses. MG induces glycation and exerts an important role in neurodegenerative and cardiovascular diseases. Isoorientin (ISO), a C-glucosyl flavone found in Aspalathus linearis, Fagopyrum esculentum, and Passiflora edulis, among others, is an antioxidant and anti-inflammatory molecule. ISO is a potent inducer of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), the master modulator of the redox environment in mammals. We investigated here whether ISO would prevent the mitochondria-related redox and bioenergetics impairments induced by MG in the human neuroblastoma SH-SY5Y cells. The cells were administrated with ISO at 20 µM for 18 h prior to the exposure to MG at 500 µM for further 24 h. It was observed that ISO efficiently prevented the mitochondrial impairments caused by MG. ISO upregulated the activity of the enzyme γ-glutamate-cysteine ligase (γ-GCL), consequently stimulating the synthesis of glutathione (GSH). The inhibition of γ-GCL, adenosine monophosphate-activated protein kinase (AMPK), and phosphoinositide 3-kinase/Akt (PI3K/Akt) suppressed the beneficial effects induced by ISO on the MG-challenged cells. Moreover, silencing of Nrf2 blocked the ISO-dependent γ-GCL and GSH upregulation and the effects on the mitochondria of the MG-challenged cells. Then, ISO caused mitochondrial protection by an AMPK-PI3K/Akt/Nrf2/γ-GCL/GSH-dependent manner in MG-administrated SH-SY5Y cells.

The isothiocyanate sulforaphane prevents mitochondrial impairment and neuroinflammation in the human dopaminergic SH-SY5Y and in the mouse microglial BV2 cells: role for heme oxygenase-1.

Sulforaphane (SFN) promotes protective effects in different cell types. Nonetheless, it remains to be clarified by which mechanism SFN exerts benefits in mammalian cells. Mitochondria are a major source of adenosine triphosphate (ATP) and reactive species in nucleated cells. Mitochondrial impairment result in cellular redox biology disruption, bioenergetic status collapse, and inflammation. Evidence suggest that mitochondrial dysfunction plays a role in neurological disorders. Since a cure was not discovered yet to some of these diseases, investigating strategies to promote mitochondrial protection is pharmacologically relevant and may improve life quality of patients suffering from these maladies. Natural molecules, such as SFN, are potent inducers of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) and, consequently, stimulate the expression of genes whose products, such as heme oxygenase-1 (HO-1), induce cytoprotective actions in mammalian tissues. In this work, we investigated whether SFN (5 µM) would be capable to prevent the dysfunctions caused by chlorpyrifos (CPF) on the human dopaminergic SH-SY5Y cells. Moreover, we examined the effects of a pretreatment with SFN at the same concentration on the mouse microglial BV2 cells stimulated by lipopolysaccharide (LPS) in an experimental model of neuroinflammation. SFN prevented the mitochondrial impairment and the neuroinflammation caused by the chemical stressors in both cell types. Inhibition of heme oxygenase-1 (HO-1) suppressed the mitochondrial protection and anti-inflammatory action afforded by SFN in this experimental model. Overall, SFN promoted cytoprotection by a mechanism dependent on the HO-1 enzyme in the SH-SY5Y and BV2 cells.

A Pretreatment with Isoorientin Attenuates Redox Disruption, Mitochondrial Impairment, and Inflammation Caused by Chlorpyrifos in a Dopaminergic Cell Line: Involvement of the Nrf2/HO-1 Axis.

The C-glucosyl flavone isoorientin (ISO) is obtained by humans from the diet and exhibits several cytoprotective effects, as demonstrated in different experimental models. However, it was not previously shown whether ISO would be able to prevent mitochondrial impairment in cells exposed to a chemical stressor. Thus, we treated the human neuroblastoma SH-SY5Y cells with ISO (0.5-20 µM) for 18 h before a challenge with chlorpyrifos (CPF) at 100 µM for additional 24 h. We observed that ISO prevented the CPF-induced lipid peroxidation and protein carbonylation and nitration in the membranes of mitochondria extracted from CPF-treated cells. ISO also attenuated the CPF-elicited increase in the production of reactive species in this experimental model. Moreover, ISO prevented the CPF-induced disruption in the activity of components of the oxidative phosphorylation (OXPHOS) system in the SH-SY5Y cells. ISO also promoted an anti-inflammatory action in the cells exposed to CPF. CPF caused a decrease in the activity of the enzyme heme oxygenase-1 (HO-1), a cytoprotective agent. On the other hand, ISO upregulated HO-1 activity in SH-SY5Y cells. Inhibition of HO-1 by zinc protoporphyrin-IX (ZnPP-IX) suppressed the cytoprotection induced by ISO in the CPF-treated cells. Besides, silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) abolished the ISO-induced HO-1 upregulation and mitochondrial benefits induced by this flavone on the CPF-challenged cells. Thus, ISO protected mitochondria of the CPF-treated cells by an Nrf2/HO-1-dependent fashion in the SH-SY5Y cells.

Suppression of Mitochondria-Related Bioenergetics Collapse and Redox Impairment by Tanshinone I, a Diterpenoid Found in Salvia miltiorrhiza Bunge (Danshen), in the Human Dopaminergic SH-SY5Y Cell Line Exposed to Chlorpyrifos.

Tanshinone I (T-I, C18H12O3) is a diterpene found in Salvia miltiorrhiza Bunge (Danshen) and promotes cytoprotection in several experimental models. Chlorpyrifos (CPF) is an agrochemical that causes bioenergetics failure, redox impairment, inflammation, and cell death in animal tissues. Here, we investigated whether T-I would be able to prevent the consequences resulting from the exposure of the human dopaminergic SH-SY5Y cells to CPF. We found that a pretreatment with T-I at 2.5 µM for 2 h suppressed lipid peroxidation and protein carbonylation and nitration on the membranes of mitochondria extracted from the CPF-treated cells. Also, T-I reduced the production of radical superoxide (O2-•) by the mitochondria of the CPF-challenged cells. The production of nitric oxide (NO•) and hydrogen peroxide (H2O2) was also decreased by T-I in the cells exposed to CPF. The CPF-induced decrease in the activity of the complexes I-III, II-III, and V was abolished by a pretreatment with T-I. Loss of mitochondrial membrane potential (ΔΨm) and reduction in the production of adenosine triphosphate (ATP) were also prevented by T-I in the CPF-treated cells. T-I also induced anti-inflammatory effects in the CPF-treated cells by decreasing the levels of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) and the activity of the nuclear factor-κB (NF-κB). Inhibition of heme oxygenase-1 (HO-1) or silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) blocked the T-I-promoted mitochondrial protection and anti-inflammatory action. Overall, T-I depended on the Nrf2/HO-1 axis to prevent the deleterious effects caused by CPF in this experimental model.

Pinocembrin pretreatment counteracts the chlorpyrifos-induced HO-1 downregulation, mitochondrial dysfunction, and inflammation in the SH-SY5Y cells.

Chlorpyrifos (CPF), an insecticide, induces pro-oxidant, pro-inflammatory, and pro-apoptotic effects in animal cells. Contamination with CPF occurs not only in farms, since CPF is found in the food consumed in homes. Recently, it was demonstrated that CPF affects the mitochondria, inhibiting components of the electron transfer chain (ETC), causing loss of mitochondrial membrane potential (MMP), and reducing the synthesis of adenosine triphosphate (ATP) by the Complex V. Pinocembrin (PB) is found in propolis and exhibits antioxidant, anti-inflammatory, and anti-apoptotic effects in mammalian cells. PB is a potent inducer of the nuclear factor erythroid 2-related factor 2 (Nrf2), which is a major transcription factor controlling the expression of heme oxygease-1 (HO-1), among others. In the present work, we investigated whether PB would be able to prevent the mitochondrial and immune dysfunctions in the human neuroblastoma SH-SY5Y cells exposed to CPF. PB was tested at 1-25 µM for 4 h before the administration of CPF at 100 µM for additional 24 h. We found that PB prevented the CPF-induced inhibition of ETC, loss of MMP, and decline in the ATP synthesis. PB also promoted anti-inflammatory actions in this experimental model. Silencing of Nrf2 or inhibition of HO-1 suppressed the PB-induced effects in the CPF-challenged cells. Thus, PB promoted beneficial effects by a mechanism dependent on the Nrf2/HO-1/CO + BR axis in the CPF-treated cells.

Astaxanthin prevents mitochondrial impairment in the dopaminergic SH-SY5Y cell line exposed to glutamate-mediated excitotoxicity: Role for the Nrf2/HO-1/CO-BR axis.

Mitochondrial dysfunction has been viewed in several diseases, including neurological disorders. In the glutamate (GLU)-mediated excitotoxicity, it has been described mitochondrial impairment, disrupted redox environment, and increased rates of cell death in the affected brain areas. Astaxanthin (AST) is a potent antioxidant and anti-inflammatory xanthophyll that also promotes beneficial mitochondria-related effects in brain cells. However, it is not completely clear how AST would be able to promote mitochondrial protection in those cell types. Thus, we investigated here how AST would protect mitochondria in the dopaminergic SH-SY5Y cell line exposed to GLU. AST was administrated to the cells at 1-40 µM for 24 h prior to the exposure to GLU at 80 mM for additional 24 h. AST prevented the GLU-induced impairment in the activity of the Complexes I and V, the loss in mitochondrial membrane potential (MMP), and the decline in the synthesis of ATP. AST also induced an antioxidant effect in the membranes of mitochondria obtained from the GLU-treated SH-SY5Y cells. Inhibition of the enzyme heme oxygenase-1 (HO-1) or silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) suppressed the AST-promoted cellular and mitochondrial protection. Either tricarbonyldichlororuthenium(II) dimer (CORM-2, a source of carbon monoxide - CO) or bilirubin (BR), that are products of the HO-1-biliverdin reductase (BVR) axis, blocked some of the effects caused by GLU in the SH-SY5Y cells. Overall, our data demonstrate that AST prevented mitochondrial dysfunction by a mechanism related to the Nrf2/HO-1 axis in GLU-challenged cells.

The signaling pathway PI3K/Akt/Nrf2/HO-1 plays a role in the mitochondrial protection promoted by astaxanthin in the SH-SY5Y cells exposed to hydrogen peroxide.

The mitochondria are the major source of reactive species in the mammalian cells. Hydrogen peroxide (H2O2) is a potent inducer of redox impairment by a mechanism, at least in part, dependent on its ability to impair mitochondrial function. H2O2 plays an important role in several pathological conditions, including neurodegeneration and cardiovascular diseases. Astaxanthin (AST) is a xanthophyll that may be found in microalgae, crustaceans, and salmon and exhibits antioxidant and anti-inflammatory effects in different cell types. Even though there is evidence pointing to a role for AST as mitochondrial protectant agent, it was not clearly demonstrated how this xanthophyll attenuates mitochondrial stress. Therefore, we investigated here whether and how AST would be able to prevent the H2O2-induced mitochondrial dysfunction in the human neuroblastoma SH-SY5Y cells. We found that AST (20 µM) prevented the H2O2-induced loss of mitochondrial membrane potential (MMP) and decrease in the activity of the Complexes I and V. AST pretreatment blocked the mitochondria-related pro-apoptotic effects elicited by H2O2. AST upregulated the enzyme heme oxygenase-1 (HO-1) and the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) by a mechanism dependent on the phosphoinositide 3-kinase/Akt (PI3K/Akt) signaling pathway. Inhibition of the PI3K/Akt or of the HO-1 enzyme abolished the AST-induced mitochondrial protection in cells challenged with H2O2. Silencing of Nrf2 caused similar effects. Thus, we suggest that AST promotes mitochondrial protection by a mechanism dependent on the PI3K/Akt/Nrf2/HO-1 signaling pathway in SH-SY5Y cells exposed to H2O2.

Rational Design, Synthesis and Evaluation of Indole Nitrogen Hybrids as Photosystem II Inhibitors.

We report the synthesis of twelve indole derivatives bearing nitro or amide groups via Fischer indole methodology followed by reduction/acetylation and amidation reactions. After thorough characterization, these indoles were subjected to a number of studies in order to evaluate their bioactive potential as photosynthesis and plant growth inhibitors. Firstly, these molecular hybrids were evaluated as photosystem II (PSII) inhibitors through chlorophyll a (Chl a) fluorescence measurement. In this study, 6-chloro-8-nitro-2,3,4,9-tetrahydro-1H-carbazole (15a) and 5-chloro-2,3-dimethyl-7-nitro-1H-indole (15b) showed the best results by reducing the phenomenological parameters of reaction centers ABS/RC, TR0 /RC and ET0 /RC of PSII. Electron chain blockage by these compounds may lead to diminished ATP synthesis and CO2 fixation which interrupt the plant development. The compounds 15a and 15b both act as postemergent herbicides, reducing the dry biomass of Ipomoea grandifolia and Senna alata weeds by an average of 40% and 37%, respectively, corroborating the fluorescence results. Additionally, the molecular docking study revealed that the presence of strong electron-withdrawing groups at the indole phenyl ring is important for the ligand's interaction with the binding pocket of protein D1 on PSII. The optimization of these molecular features is the goal of our research group in further understanding and development of new potent herbicides.

Synthesis and evaluation of indole derivatives as photosynthesis and plant growth inhibitors.

Indole derivatives were synthetized based on the Fischer indole methodology using different phenyl hydrazine hydrochlorides and either cyclohexanone or 2-butanone. The pre- and post-emergent herbicidal activities were evaluated against Ipomoea grandifolia. A carbazole, 6-chloro-2,3,4,9-tetrahydro-1H-carbazole (3b), decreased the PIabs parameter by 32% and increased the cross-section related parameters, indicating the inactivation of the reaction center on photosystem II. Compound 3b acts as a post-emergent herbicide prototype since dry biomass was reduced by 50%, corroborating the fluorescence results. Comparing instead with a germination experiment, 2,3,4,9-tetrahydro-1H-carbazole (3a) was found to be the most effective agent, inhibiting seed germination by 22% and decreasing root length by 50%. The tetrahydrocarbazoles showed better results than indole derivatives potentially due to the presence of methylene groups at structures, which increase the compounds' lipophilicity and may facilitate their access to the plant. In addition, electron withdrawing groups on the aromatic ring were found to correlate with increased herbicide activity. Further optimization of this series towards the development of herbicides is ongoing.

Acute and subchronic antihyperglycemic activities of Bowdichia virgilioides roots in non-diabetic and diabetic rats.

AIM: The present study was undertaken to evaluate the acute and subchronic antihyperglycemic effects of methanolic extract of Bowdichia virgilioides root bark of B. virgilioides in streptozotocin (STZ)-induced diabetic rats. MATERIALS AND METHODS: The extract (100, 250 or 500 mg/kg) was orally administered to male Wistar diabetic (STZ, 42 mg/kg i.v.) and non-diabetic rats into two main protocols: (i) subchronic experiments, where animals were treated for 21 days with B. virgilioides extract and the following parameters were evaluated: Body weight, fluid and food intake (determined daily), urinary glucose and urea (every 3 days) and glycemia (every 5 days). At the end of the experimental period, skeletal muscles (extensor digitorum longus [EDL] and soleus), retroperitoneal and epididymal white adipose tissues were collected and weighed; liver samples were used for the determination of the lipid and glycogen contents; (ii) acute experiments, which evaluated the alterations on fasting and post-prandial glycemia and on glucose tolerance using the oral glucose tolerance test (OGTT). RESULTS: In subchronic experiments, the treatment with B. virgilioides extract did not change any parameter evaluated in diabetic and non-diabetic animals. On fasting and post-prandial glycemia, the extract treatment did not promote changes in the glycemia values in diabetic or non-diabetic animals. In OGTT, the treatment with 500 mg/kg B. virgilioides extract reduced the hyperglycemia peak after a glucose overload, when compared with non-treated diabetic animals, resulting in a lower area under curve. CONCLUSION: The results of our work indicate that B. virgilioides root extract promotes an acute antihyperglycemic effect in STZ-diabetic rats; this effect probably occurs through an inhibition of the intestinal glucose absorption. The continuity of the research is necessary to elucidate these possibilities.

Evaluation of toxicity of Calophyllum brasiliense stem bark extract by in vivo and in vitro assays.

ETHNOPHARMACOLOGICAL RELEVANCE: Calophyllum brasiliense Camb., Clusiaceae, is commonly known as "guanandi" and its stem bark is used in Brazilian traditional medicine to treat rheumatism, vein problems, hemorrhoids and gastric ulcers. The aim of this study was to evaluate the toxicity of hexane extract of Calophyllum brasiliense stem bark (HECb) using in vitro and in vivo experimental models. MATERIALS AND METHODS: In vitro toxicity was evaluated by Alamar Blue cytotoxicity assay and micronucleus test, using Chinese hamster ovary (CHO-k1) epithelial cells. in vivo toxicity was evaluated by oral acute and subchronic toxicity assays. In the oral acute toxicity screening, a single dose of HECb was administered to mice at doses ranging from 250 to 1000 mg/kg. In the subchronic study, HECb was administered orally for 30 days to Wistar rats at doses of 100 mg/kg and 500 mg/kg. Phytochemical analyses were performed by HPLC/UV-vis, secondary metabolites were quantified by spectrophotometric methods. RESULTS: HECb presented IC50=119.94±4.31 µg/mL after a 24 h cytotoxicity test using CHO-k1 cells, showing low cytotoxicity. However, when the cells were exposed to HECb for 72 h, the IC50 value was 8.39±2.00 µg/mL, showing in this case, a pronounced cytotoxic effect. In the oral acute toxicity studies, doses up to 500 mg/kg of HECb did not cause any changes in both male and female mice. At 1000 mg/kg, male mice showed signs typical of depression and stimulation that were reversed at 72 h. Besides, female mice were more sensitive to the toxic effect of HECb at 1000 mg/kg, which initially presented typical agitation signals, followed by depression signals, leading to death of all the animals at 24h. In subchronic assay with rats, HECb administered orally at doses of 100 and 500 mg/kg did not cause significant changes in all clinical parameters evaluated. Histopathological analyses showed no deleterious effect in the vital organs of rats. Preliminary phytochemical analysis revealed the presence of phenolic compounds, steroids, and volatile coumarins. Analysis by HPLC showed two major peaks characteristic of chromanones. CONCLUSIONS: In vitro toxicological tests showed that HECb exhibited cytotoxicity especially after 72 h of exposition, and mutagenicity on the highest tested dose. The in vivo studies demonstrated that HECb produced some toxicity signs at the highest dose tested, particularly, in the acute toxicity test but showed no significant signs of toxicity in the subchronic assay. Based on these and previous pharmacological studies, it is possible to say that HECb did not exhibit significant toxicity at its effective dose. This suggests that HECb is relatively safe in humans at its effective dose.

Evaluation of antiulcer activity of chromanone fraction from Calophyllum brasiliesnse Camb.

ETHNOPHARMACOLOGICAL RELEVANCE: Calophyllum brasiliense Camb. (Clusiaceae), popularly known as 'guanandi', is found in the tropical areas and swampy lands. The latex exuding from its bark is used in the treatment of gastric ulcer in folk medicine. Several active compounds have been isolated from its stem bark among them, are the chromanone acids. Therefore, this study aimed to evaluate antiulcer activity and probable mechanism(s) of action of a fraction containing a mixture of chromanone acids (BI), derived by column chromatography fractionation of the hexane extract of the stem bark of Calophyllum brasiliense (HECb), using experimental in vitro and in vivo models. MATERIALS AND METHODS: Ulcer was induced by oral administration of ethanol (75%, v/v) and indomethacin (50mg/kg). Malondialdehyde, reduced glutathione and catalase activity was measured in stomach tissue after ethanol induced ulcer. In order to evaluate the effect of BI on nitric oxide, ulcer was induced by ethanol in l-NAME pretreated animals. Anti-Helicobacter pylori activity was verified in disk diffusion and broth microdilution in vitro assays, using cagA+ and vacA+ Helicobacter pylori strains. RESULTS: BI prevented the gastric ulceration caused by ethanol and indomethacin treatments. Its gastroprotective mechanism in ethanol-induced ulcer was partly due to reduction of MDA and CAT levels in the gastric tissue. BI did not affect the GSH levels and its gastroprotective effect was not reversed by pretreatment with l-NAME. BI showed anti-Helicobacter pylori in the both assays. CONCLUSION: The results indicate that BI is partly responsible for the HECb antiulcer and anti-Helicobacter pylori effects.

Mechanism of anti-hyperglycemic action of Vatairea macrocarpa (Leguminosae): investigation in peripheral tissues.

AIM OF THE STUDY: Previous studies in our laboratory have demonstrated that the treatment of diabetic rats during 21 days with V. macrocarpa stem-bark ethanolic extract (VmE), reduced glycemia, urinary glucose and urea, increased liver glycogen content and improved other parameters diabetes related. The objective of this study was to evaluate if the anti-hyperglycemic mechanisms of VmE could be caused by improvement in the insulin signaling pathway in the peripheral tissues (liver, adipose and skeletal muscle). MATERIAL AND METHODS: Streptozotocin-diabetic rats were separated into two groups: diabetic control (DC) and diabetic treated with VmE (DT) during 21 days. The alterations on the insulin signaling in liver, retroperitoneal adipose tissue (RET) and extensor digitorum longus (EDL) muscles were investigated through determination of insulin receptor (IR), protein kinase B/AKT content and AKT phosphorylation levels using Western blotting analysis. This same methodology was used to evaluate the phosphoenolpyruvate carboxykinase (PEPCK) levels in the liver from these animals. RESULTS: The treatment with the extract increased the content of IR and the basal phosphorylation of AKT in the three tissues. In the liver from diabetic treated group, the insulin-stimulated AKT phosphorylation was higher and the PEPCK protein levels were reduced. CONCLUSIONS: Data from this work suggest that the anti-hyperglycemic activity of stem-bark extract of V. macrocarpa can occur through stimulation of insulin signaling pathways in peripheral tissues from diabetic rats, mainly in liver and adipose tissue, probably promoting increase in the glucose uptake and liver glycogen synthesis. The concomitant decreasing in hepatic PEPCK levels could be associated to inhibition of gluconeogenesis, which can also contribute to glycemia reduction.

Diaqua-bis[2,5-dichloro-N-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)benzene-sulfonamidato-κN]zinc(II).

In the title compound, [Zn(C(17)H(14)Cl(2)N(3)O(3)S)(2)(H(2)O)(2)], the Zn(II) ion has a tetra-hedral coordination formed by the two N atoms of the sulfonamide groups and the two water mol-ecules. Two inter- and two intra-molecular O-H⋯O hydrogen bonds are observed in the crystal structure.

N-(1,5-Dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-methyl-benzene-sulfonamide.

In the title compound, C(18)H(19)N(3)O(3)S, the phenyl ring and the pyrazole ring are twisted with respect to each other by an angle of 49.11 (7)°. The C-N-S-C torsion angle is -122.5 (2)°. The methyl group bonded to the N atom of the pyrazole ring has a large deviation from the mean ring plane of 0.603 (3) Å. One inter-molecular N-H⋯O and two non-classical inter-molecular C-H⋯O hydrogen bonds are observed in the crystal structure.