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Objective: Microbial infections and the cancer are the biggest health concerns now days. It has been reported that 19.3 million new cancer cases and approximately 10 million deaths occurred due to cancer. The pyrimidine and their derivatives have been investigated a lot by the researchers due to their versatile chemotherapeutic effects. The unmet demand for the new antimicrobial and anticancer chemotherapeutic agents and the versatile pharmacological applications of pyrimidine derivatives prompted us to perform the synthesis and biological assessment of some novel 3-(substitued)-6-(substituted)pyrimidin-2-yl)-2-phenylthiazolidin-4-one. Methods: As a part of or investigation to find out some novel antimicrobial and anticancer agents, in this paper we focused on the synthesis of some novel 3-(substitued)-6-(substituted)pyrimidin-2-yl)-2-phenylthiazolidin-4-one derivatives. Additionally, the compounds were screened virtually for the drug likeness properties and characterized by FT-IR and NMR. Antimicrobial and anticancer studies were performed using the methods of disc diffusion, macro dilution and MTT assay. Results and Discussion: The virtual screening results revealed that all the compounds were found under the zone of inhibition for an active drug molecule. It was observed that the analytical data strongly supported the structure of the aimed compounds. Among all the synthesized compounds, the compounds (IX–XII), (XIV–XVI) were possessed very good antimicrobial effects. Some of these members represented even better antimicrobial potential against some specific pathogens. The compound (XII) was observed to be the most active compound of the series against almost all bacterial pathogens. The MTT findings revealed that the compounds (III), (IX), (X), (XII) were possessed similar IC50 to the reference drug doxorubicin. Conclusions: The antimicrobial and anticancer findings were promising and it was believed that further studies with these compounds aiming in vivo analysis will be helpful in producing the novel antimicrobial and anticancer agents. [ABSTRACT FROM AUTHOR]

Herein we report the synthesis and biological evaluation of a new series of thiazolidin-4-one derivatives. The C4 and C5 functionalized, 5-arylidene/alkylidene, 5-bromo, 5-pyridinium, and 4-arylimino analogs of thiazolidine-4-one were prepared efficiently using appropriate synthetic routes and characterized by IR, NMR and Mass spectrometry. Results of antimicrobial evaluation showed that compounds 4 and 8 had significant antibacterial activity comparable to that of the reference drug gentamicin. Compound 5a showed promising antifungal activity compared to amphotericin B as a reference drug. The antitumor activity revealed that compound 4 was the most active analog among the tested series with IC50 values of 28.4 and 12.6 µg/mL against both HCT-116 and HepG-2 cell lines, respectively, compared to standard drug doxorubicin. Results from the biological evaluation, in-silico molecular docking studies, and ADMET analyses confirmed that thiazolidin-4-one is a promising scaffold that can be used to design potential lead compounds for the antibacterial and antitumor agents. [ABSTRACT FROM AUTHOR]

In this contribution, new derivatives of bicyclic fused rings with a bridgehead nitrogen atom were synthesized from the imidazo[1,2-a]pyridine derivatives C1 by reacting two moles of 2-aminopyridine and 4-aminoacetophenone with iodine in a one-pot reaction. This compound (C1) was then condensed with 2- nitrobenzaldehyde and 2,4-dichlorobenzaldehyde to form new derivatives of Schiff bases (C2 and C3). These Schiff bases were then cyclized to synthesize thiazolidin4-one derivatives (C4 and C5), tetrazole derivatives (C6 and C7), and aza-β-lactam derivatives (C8 and C9) through the reactions with thioglycolic acid, sodium azide, and 1-naphthylisocyanate, respectively. FT-IR, 1H NMR, and 13C NMR spectroscopy were used to characterize these new compounds. In the second part of this work, the antioxidants of these compounds were measured, and results ranged from good to medium. [ABSTRACT FROM AUTHOR]

Thiazolidin-4-ones have a broad range of medical and clinical implementation, which is important for pharmaceutical and medicinal chemistry. This heterocyclic core has been reported to possess a diversity of bioactivities, including antimicrobial and antibiofilm-forming potential. The resistance of biofilms to antibiotics or disinfectants is a serious medical problem. Therefore, there is a natural need to discover new effective structures with properties that inhibit biofilm formation. This review aims to analyze the antibiofilm features of thiazolidin-4-ones described in the literature over the last two decades. The information gathered in this review could benefit the rational design of new effective antibiofilm small molecules with thiazolidin-4-one cores. [ABSTRACT FROM AUTHOR]

Thiazolidin‐4‐one is a versatile nucleus that has been reported to exhibit a diverse array of biological activities, including anticancer and antimicrobial activities. In the current research study, a series of C2‐(p‐substituted phenyl)‐thiazolidin‐4‐one compounds conjugated with anilines were designed and tested for drug‐likeness behaviour. Subsequently, the designed compounds were synthesized, characterized, and tested for anticancer activity against three cancer cell lines, namely liver (HEP−G2 cells), breast (MDA‐MB‐231), and glioblastoma (U87MG cells), with gemcitabine as the reference positive control drug. Initially, the compounds were tested at 50 micromolar, while the MIC was determined for the selected active compounds. Among the three cell lines, MDA‐MB‐231 showed relatively higher sensitivity towards the tested compounds. Four compounds of the series exhibited comparable or superior cytotoxicity to the reference drug gemcitabine. Particularly, N‐(p‐tolyl)‐2‐(2‐(4‐methoxyphenyl)‐4‐oxothiazolidin‐3‐yl)acetamide (6 d) displayed highest cytotoxicity among the series. The anticancer activity of the selected compounds was also tested against 3D spheroid models, in which compound N‐(4‐chlorophenyl)‐2‐(2‐(4‐methoxyphenyl)‐4‐oxothiazolidin‐3‐yl)acetamide (6 a) induced apoptosis in brain tumour spheroids (MTS). Docking studies of compound 6 d were performed against different targets, namely dihydrofolate reductase, phosphoinositide 3‐kinase, epidermal growth factor receptor, dihydroorotate dehydrogenase, and murine double minute 2, which illustrated inhibition of dihydroorotate dehydrogenase as a possible mechanism of toxicity. The compounds were also evaluated in vitro for antibacterial activity against two bacterial strains (E. coli and P. aeruginosa) and a Candida albicans fungal strain. [ABSTRACT FROM AUTHOR]

Antibiotic resistance has emerged as a formidable public health challenge, being recognized as a paramount priority demanding urgent resolution. Consequently, to augment the therapeutic armamentarium in combating recalcitrant microorganisms, the synthesis of novel molecules derived from pre-existing drugs has demonstrated substantial promise as an alternative approach. Herein, five novel thiazolidin-4-one derivatives based on sulfamethoxazole were successfully synthesized. The chemical structures were well characterized using FT-IR, 1H NMR, and 13C NMR and CHNS. Adjectives are predicted for ADMET properties and study the molecular docking for synthesis derivatives, percentage hemolysis ratio was within range (2.5–60%). Biological activity was also evaluated against two types of bacteria, Pseudomonas aeruginosa and Staphylococcus aureus, the results show that the synthesis compounds have good activity against Pseudomonas aeruginosa. Liver enzymes results show that synthesis compounds have a significant effect on raising liver enzymes compared with the reference and the healthy person. [ABSTRACT FROM AUTHOR]

This study reports a facile mechanochemical conversion of N-phenylthiosemicarbazone derivatives of 1-tetralone analogs into thiazolidin-4-ones, thiazolidin-5-ylidene-acetates, and dihydrothiazoles by their condensation with chloroacetic acid, DMAD, and phenacyl bromide, respectively. Triethylammonium hydrogen sulfate [Et3NH]+ [HSO4]− is employed as solid catalyst for this prompt and ecological conversion through which the target products are formed within 10–30 minutes in quantitative yields. The products have been characterized on the basis of spectroscopic data. X-ray diffraction studies of thiazolidin-5-ylidene-acetate 5b, supported by DFT calculations of E/Z isomers of 5b, are presented. Compounds 4, 5, and 7 are assayed for their antibacterial prospects against Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) bacterial stains. Some derivatives show highly promising antibacterial activities. [ABSTRACT FROM AUTHOR]

In this innovative research, a novel series of thiazolidin-4-one analogues having a 1,3,4-oxadiazole/thiadiazole moiety were derived and the structures of all the newly obtained molecules were established using different physicochemical and analytical means (1H-NMR, FTIR, mass spectra, and elemental analyses). The synthesized molecules were then investigated for their antiproliferative, antimicrobial, and antioxidant potential. The cytotoxicity screening studies revealed that analogues D-1, D-6, D-15, and D-16 possessed comparable efficacy, within the IC50 range (1 to 7 μM), when taking doxorubicin as a reference drug (IC50 = 0.5 μM). The antimicrobial activity was assessed using different Gram-(+) and Gram-(−) bacterial and fungal strains and the results revealed that molecules D-2, D-4, D-6, D-19, and D-20 possessed potent activity against selective strains of microbes with MIC ranges of 3.58 to 8.74 µM. The antioxidant evaluation was performed using the DPPH assay and the screening results revealed that analogue D-16 was the most potent derivative (IC50 = 22.3 µM) when compared with the positive control, ascorbic acid (IC50 = 111.6 µM). Structure–activity relationship (SAR) studies of the synthesized novel derivatives revealed that para-substituted halogen and hydroxy derivatives have remarkable potential against the MCF-7 cancer cell line and antioxidant potential. Similarly, electron-withdrawing groups (Cl/NO2) and -donating groups at the para position possess moderate to promising antimicrobial potential. [ABSTRACT FROM AUTHOR]

In this study, 16 new compounds were synthesized starting from methylparaben. These new compounds consist of eight arylidenehydrazide derivatives and eight thiazolidin‐4‐on derivatives. All compounds were tested against MCF‐7 breast cancer cells and MCF10A breast healthy tissue to determine their anti‐cancer activity. Molecular docking studies were also carried out against receptor proteins related to the growth factor of cancer cells to understand inhibition mechanism. According to the results, 4‐furan‐2‐ylmethoxy)‐N‐(4‐oxo‐2‐phenylthiazolidin‐3‐yl)benzamide (5 a) and 4‐(furan‐2‐ylmethoxy)‐N‐(2‐(4‐nitrophenyl)‐4‐oxothiazolidin‐3‐yl)benzamide (5 e) were found as the highest selective and most active compounds against breast cancer cells. [ABSTRACT FROM AUTHOR]

A new design of thiazolidin-4-one derivatives were evaluated for their cytotoxicity on CHO (Chinese Hamster ovary cells), SKOV3 (Human Ovarian cancer) and HeLa (Human cervical) cancer cell lines. All these compounds exhibited moderate cytotoxicity against CHO cells but showed potent anticancer activity against both SKOV3 and HeLa cell lines. A high antiproliferative activity of compound (Va), (Vd) and (Vm) against SKOV3 and (Va), (Vm) and (Vq) against HeLa cell lines were observed. It is interesting to note that (Vq) and (Vc) are comparatively lesser toxic to the normal CHO cells but highly cytotoxic against HeLa and SKOV3 cells. In the antimicrobial activity (Vb), (Vc) and (Vq) compounds displayed a moderately antifungal activity against Aspergillus niger and A. flavus at 150 μg/mL concentration. Moreover, molecular docking and molecular dynamics analysis over 100 ns with target FGFR2 (4j96): (Vq) retained good acceptable profiles for stability of this complex. Based on these bioactivity studies, it is indicated that (Vb) and (Vq) compounds can be potential substitutes for the treatment of ovarian and cervical cancer respectively because of their high specificity to both types of ovarian and cervical cancers with minimal toxicity to normal cells. [ABSTRACT FROM AUTHOR]

The preparation, characterization, and catalytic investigation of NiFe2O4@SiO2 grafted 3-(propyl azanediyl)bis(ethane-2,1-diyl) bis(hydrogen sulfate) nanoparticles (A) is described. The catalyst was characterized by FT-IR, XRD, FE-SEM, and DLS techniques. The main particle size by the DLS technique was determined as 52 nm. The catalyst was found to be efficient for the condensation of 9-methyl-9H-carbazol-3-amine, thioglycolic acid, and aldehydes lead to the formation of 3-(9-methyl-9H-carbazol-3-yl)-2-arylthiazolidin-4-one derivatives (1d-11d) under reflux in DMF DMF (Time: 1–2 h; Yields: 76–98%) and ultrasonic irradiation in DMF (Time: 0.8–1 h; Yields: 85–97%). The effect of solvent, temperature, and catalyst dosage on the reaction was studied. The catalyst can be recovered and reused 11 times. [ABSTRACT FROM AUTHOR]

Thiazolidin-4-ones is a versatile and privileged nucleus comprising of a five five-membered heterocyclic ring system possessing sulphur heteroatom and a cyclic amide bond. Extensive research and review studies mainly published in the last decade explored the diverse types of biological activities of this nucleus with potential therapeutic applications. Various silent features like drug likeness behaviour, suitability for diversity-oriented synthesis, and its sensitivity toward the redox tumour microenvironment makes it an attractive scaffold for anti-cancer drug discovery. Thiazolidine-2,4-dione and thiazolidine-4-ones are the two classical variants of thiazolidine scaffold, the former is more explored in comparison to thiazolidine-4-one. However, thiazolidine-4-one nucleus is also getting the attention of researchers, evident by the various research studies, mainly published in the last few years. The current comprehensive review focuses on its anti-cancer potential, covering structural diversity and substitution patterns among diverse derivatives containing this nucleus as a core skeleton. This review also gives impetus to the different enzymatic targets, exploited for drug discovery, relative selectivity in cancerous tissue compared to healthy counterpart cells, structure-activity relationship (SAR), and future perspectives for translational research. To generate potential lead candidates with the translational outcome next level studies like pharmacokinetic and metabolic stability are suggested. [ABSTRACT FROM AUTHOR]

The overexpression of Rab proteins was linked to cancer development, making this family of proteins an attractive drug target for the identification of novel inhibitors against tumor diseases. In this study, novel triazole-based azomethine/thiazolidin-4-one hybrid analogs were designed, prepared and structurally confirmed by using elemental and spectral techniques, these include FT-IR, MS, and NMR spectra. In addition, in vitro cytotoxic activity was assessed against NCI-60 cancer cell lines. To understand the possible mode of action and drugability, molecular docking studies and drug-likeness were achieved. The docking simulations were performed against various Rab family proteins Rab2a, Rab25, Rab5, and Rab35; promising targets for cancer medication to support the cytotoxicity findings and to further validate the action of new molecules. Furthermore, in silico ADMET screening of the molecules was within the recommended values stated by Lipinski’s rule of five (Ro5), indicating their oral bioavailability and therapeutic potentials. Among the newly prepared analogs tested, compounds 4d and 3d exhibited significant antitumor activity against breast, ovarian, lung, and leukemia cancer cell lines. Our findings suggested that azomethine/thiazolidin-4-one moieties incorporated triazole analogs are a promising class of molecular entities for the development of new anticancer therapies, through targeting of some Rab proteins. [ABSTRACT FROM AUTHOR]

The article presents the synthesis and liquid crystalline properties of some of new bent and linear core compounds containing a 1,3,4-oxadiazole, piperazine and thiazolidin-4-one rings as a central core. The new synthesized compounds were characterized by elemental analysis and FTIR, 1HNMR and mass spectroscopy). The liquid crystalline properties were studied by polarized optical microscopy and differential scanning calorimetry. All Schiff bases compounds with 1,3,4-oxadiazole and piprzaine ring in central core presented liquid crystalline properties. The liquid crystallinity of compounds containing 1,3,4-oxadiazole and thiazolidin-4-one rings as a central core were found depending on the type of terminal substituents. [ABSTRACT FROM AUTHOR]

Introduction: Aurora-A kinase is associated with the Aurora kinase family which has been considered a striking anticancer target for the treatment of human cancers. Objective: To design, synthesize, anticancer evaluation, and docking studies of novel 2-(1-isonicotinoyl-3-phenyl-1H-pyrazol-4-yl)-3-phenylthiazolidin-4-one derivatives as Aurora-A Kinase inhibitors. Method: A total of 21 Pyrazole derivatives P (1–21) were synthesized by using the Vilsmeier Haack reagent which was characterized by FT-IR, 1H NMR, 13C NMR, and Mass spectroscopy. The synthesized derivatives were evaluated for their potential in vitro anticancer activity by MTT assay and Aurora-A kinase inhibition assay. Results: The cytotoxicity assay (MTT assay) showed that compound P-6 exhibited potent cytotoxicity (IC50 = 0.37–0.44 μM) against two cancer (HCT 116 and MCF-7) cell lines, which were comparable to the standard compound, VX-680. Compound P-6 also showed inhibition of Aurora-A kinase with an IC50 value of 0.11 ± 0.03 µM. A Docking study was done to compound P-6 and P-20 into the active site of Aurora A kinase, in order to get the probable binding model for further study. Conclusion: A series of 21 novel pyrazole derivatives P(1–21) were designed, synthesized, in vitro anticancer evaluation, and docking studies for Aurora A kinase inhibition. The results established that P-6 is a prospective aspirant for the development of anticancer agents targeting Aurora-A kinase. [ABSTRACT FROM AUTHOR]

• Synthesis and testing of 1,4-benzodioxin derivatives containing the thiazolidin-4-one skeleton for antimicrobial activity: This finding is of great significance in the search for new antimicrobial drugs, providing potential candidate compounds for effective antimicrobial agents. • Revealing the antimicrobial mechanism through molecular docking with FabH: This discovery contributes to a deeper understanding of the antimicrobial mechanism of carbazole compounds and offers guidance for further optimization and design of compounds with higher antimicrobial activity. • Evaluation of compound's inhibition and disruption of biofilms: This finding is of significant importance as bacterial biofilms pose a serious challenge to antimicrobial drugs, and 1,4-benzodioxin derivatives may provide a new therapeutic strategy to overcome this challenge. In this study, we synthesized a variety of 1,4-benzodioxin derivatives containing the thiazolidin-4-one skeleton and evaluated their antimicrobial properties. Several of the newly synthesized compounds exhibited potent inhibitory effects against the Gram-negative bacteria Escherichia coli. By conducting molecular docking simulations and molecular dynamics with the fatty acid synthesis enzyme FabH, we unveiled the potential antimicrobial activity of these compounds, suggesting they interfered with fatty acid biosynthesis pathways. Additionally, we optimized compound 3b and assessed its ability to disrupt biofilms using live/dead cell staining techniques. The results highlighted significant biofilm disruption, enhancing the compounds' antimicrobial efficacy. These findings provided valuable insights for the development of novel antimicrobial agents and presented a promising avenue for addressing antimicrobial resistance through innovative therapeutic approaches. [ABSTRACT FROM AUTHOR]

A variety of novel thiazolidin‐4‐one himachalene derivatives were designed and synthesized through hetero‐cyclization of thiosemicarbazone analogs that have previously exhibited strong anticancer activity. The synthesized products 2 a–4 f were completely characterized by 1H NMR, 13C NMR, IR, and HRMS and were later submitted for in vitro evaluation of their anticancer activity and cytotoxicity on a panel of four human cancer cell lines (i.eHT‐1080, MCF‐7, A‐549, and MDA‐MB‐231). Most of the evaluated compounds showed potent antiproliferative activities against the four human cancer cell lines with tested IC50 values ranging from 5.25±0.32 to 9.26±0.73 μM. The mechanism of action revealed that compounds 2 b and 4 b induced caspase‐3/7‐activated apoptosis and cell cycle arrest in the G0/G1 stage in HT‐1080 and A‐549 cells. Furthermore, molecular docking studies were conducted to evaluate the binding affinities and the possible binding modes of the top‐performing compounds 2 b and 4 b. This was later supported by Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis predicting their prospective pharmacological profiles. The outcome of this study supports the validity of our strategy and presents 2 b and 4 b as a pattern for the discovery of novel cancer therapeutics. [ABSTRACT FROM AUTHOR]

Aseries of compounds based on 1-thia-4,8-diazaspiro[4.5]decan-3-one was synthesized. Their activity as new anti-ulcer agents was investigated in vivo. 8-Benzyl-4-[3-(dimethylamino)propyl]-1-thia-4,8-diazaspiro-[4,5]decan-3-one, 8-benzyl-4-[2-(dimethylamino)ethyl]-1-thia-4,8-diazaspiro[4,5]decan-3-one, 4,8-dibenzyl-1-thia-4,8-diazaspiro[4,5]decan-3-one, and 8-benzyl-4-[3-(dibutylamino)propyl]-1-thia-4,8-diazaspiro[4,5]-decan-3-one were found to possess anti-ulcer activity comparable with that of omeprazole. [ABSTRACT FROM AUTHOR]

The article presents the synthesis and liquid crystalline properties of some of new bent and linear core compounds containing a 1,3,4-oxadiazole, piperazine and thiazolidin-4-one rings as a central core. The new synthesized compounds were characterized by elemental analysis and FTIR, 1HNMR and mass spectroscopy). The liquid crystalline properties were studied by polarized optical microscopy and differential scanning calorimetry. All Schiff bases compounds with 1,3,4-oxadiazole and piprzaine ring in central core presented liquid crystalline properties. The liquid crystallinity of compounds containing 1,3,4-oxadiazole and thiazolidin-4-one rings as a central core were found depending on the type of terminal substituents. [ABSTRACT FROM AUTHOR]

The hydrothermal synthesis of ZnO–NiO–NiFe2O4 nano-composite is reported. The sample was utilized to characterize via XRD, FE-SEM, EDS, FT-IR, UV–Vis, and BET techniques. The sample consisted of three different phases as ZnO (hexagonal), NiO (cubic), and NiFe2O4 (cubic) with the average particle size as 34 nm and specific surface area, average pore diameter, and pore volume as 64.35 m2 g−1, 13.02 nm, and 0.201 cm3 g−1, respectively. Catalytic behavior of the nano-composite was investigated on the synthesis of thiazolidin-4-one derivatives under thermal and ultrasonic irradiation condition. Our results show that the catalytic activity of ZnO–NiO–NiFe2O4 nano-composite is much higher than ZnO, NiO, and NiFe2O4 metal oxides. All products were prepared in high yields with short reaction times. In addition, the catalyst was recovered for at least five times. [ABSTRACT FROM AUTHOR]

Aim. Synthesis, structure determination, in vivo study of anti-inflammatory (anti-exudative) and ulcerogenic activity, estimation of an impact of novel pyrazolin-5-one bearing thiazolidin-4-ones on liver function. Methods. Organic synthesis: multicomponent reactions (MCRs), [2+3]-cycloaddition reactions. Spectral methods: IR, LC-MS, 1H NMR. Biological methods: study of anti-cancer activity (NCI NIH, USA) protocol for 3-cell line panel); carrageenin-induced inflammatory paw edema model of white rats, biochemical laboratory tests (ALT, AST, ALP, γ-GGT levels determination); evaluation of ulcerogenic action. Results. The series of novel C-5 and N-3 substituted 2-[(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) amino/imino]thiazolidin-4-ones had been synthesized using MCR and [2+3]-cycloaddition reactions as potential biologically active compounds. The results of screening anti-exudative activity revealed that the tested derivatives possess promising anti-inflammatory effect. The SARs were formed and possible mechanisms of their action were discussed. Conclusions. The results presented in paper suggest that the design and synthesis of new pyrazolin-5-on/thiazolidin-4-one hybrids as potential molecules are an attractive area for the search for novel agents with promising pharmacological properties. [ABSTRACT FROM AUTHOR]

The present study enumerates the discovery and development of novel thiazolidin‐4‐one‐1,3,5‐triazine as neuro‐protective agent against cerebral ischemia–reperfusion injury in mice. These compounds showed significant inhibition of NF‐ĸB transcriptional activity in LPS‐stimulated RAW264.7 cells, displaying compound 8k as most potent inhibitor among the tested derivative. The compound 8k was further studied in in vivo middle cerebral artery occlusion (MCAO) mice model for neuro‐protective action. Results suggest that compound 8k causes attenuation of inflammation (TNF‐α, IL‐β, and IL‐6), oxidative stress (SOD, GSH, and MDA), and apoptosis (Bcl‐2, Bax, and cleaved caspase‐3) in MCAO mice in concentration‐dependent manner. Collectively, our results documented that compound 8k pre‐treatment protects cerebral I/R. This novel lead scaffold may be helpful for investigation of new neuro‐protective agent by inactivation of NF‐ĸB. [ABSTRACT FROM AUTHOR]

A library of novel naphthyl bearing 2‐iminothiazolidin‐4‐ones (2‐ITZDs) (2 a–2 q) was designed and synthesized through a facile route involving regioselective heterocyclization of unsymmetrical thioureas (1 a–1 q). The synthesis was achieved at ambient temperature in good to excellent yields under catalyst free conditions. The molecular structures of 2‐ITZDs were elucidated by spectroscopic techniques such as FT‐IR, 1H‐NMR and 13C‐NMR. X‐ray structural data was used to establish the structure (2 o) unequivocally and to define the geometry of exo double bond. The in vitro anticancer activity of 2‐ITZDs (2 a–2 q) was investigated in several human cancer cell lines (A549, LNCap, PC‐3, MDA‐MB‐231, BxPC3, MIA PaCa2). All compounds showed cytotoxicity with IC50 values ranging from 6–23 μM in the tested cancer cell lines except MDA‐MB‐231. Compound 2 k (IC50=7 μM) and the homologous analog 2 q (IC50=6 μM) were found to be equipotent to 2 k and showed moderate cytotoxicity against human breast cell line (DA‐MB‐231). Furthermore, compound 2 k exhibited a medium permeability, enough metabolic stability and no significant inhibition of hERG channel. Compound 2 k inhibited cytochrome P450 activity below 50 % in 1 A2, 3 A4 and 2 C19, but not in 2 C9 and 2D6 at 10 μM. Structure‐activity relationships (SAR) provided useful insights towards this class of compounds and tiled a way to design novel analogues with increased potency. [ABSTRACT FROM AUTHOR]

A series of new antipyrine derivatives containing thiazolidin-4-one ring system were synthesized via the cycloaddition reaction of a series of Schiff bases 1a-e with mercaptoacetic acid under reflux conditions. The structure of the new antipyrine derivatives 2a-e was confirmed by spectral data. In addition, the cytotoxic activity of the target compounds 2a-e was investigated in vitro against breast carcinoma cell line (MCF-7). In general, the bioassay results revealed that the synthesized compounds 2a-e have a promising reducing tumor growth comparison to the normal cells. [ABSTRACT FROM AUTHOR]

In the current project, three pharmacophores; 1,2,3-triazole, furan and thiazolidin-4-one were combined in the same matrix via a multi-step reaction. The key starting materials 5-methyl-1-phenyl-1H-1,2,3-triazole-4-carbohydrazide derivatives 3a-d were synthesized via reaction of their corresponding esters 2a-d with hydrazine hydrate. A condensation reaction of compounds 3a-d with furfural afforded the intermediate compounds 4a-d that were cyclized with thioglycolic acid under reflux condition to obtain N-(2-(furan-2-yl)-4-oxothiazolidin-3-yl)-5-methyl-1-(phenyl)-1H-1,2,3-triazole-4-carboxamide derivatives 5a-d. All the synthesized compounds were characterized by FT-IR, ¹H-NMR, 13NMR and Mass spectroscopies. The final compounds 5a-d were screened for their in vitro antioxidant activity by using DPPH radical scavenging assay. [ABSTRACT FROM AUTHOR]

Aim. Synthesis and in vivo study of acute toxicity, anti-inflammatory (anti-exudative) activity and side effects of pyrazoline-thiazolidin-4-one hybrid Les-5581 under conditions of therapeutic use in experimental animals. Methods. Traditional organic synthesis. The Litchfield- Wilcoxon method. Carrageenin- and formaldehyde-induced inflammatory paw edema models of white rats. Clinical laboratory tests: study of general blood parameters and biochemical profile of liver function (ALT, AST, LF and γ-GGT levels). Evaluation of ulcerogenic action. Results. The target hybrid Les-5581 has been synthesized in a convenient and efficient aminolysis of 5-etoxymethylidenerhodanine by 3,5-bis-(4-chloro-phenyl)-4,5-dihydro-1H-pyrazole. The LD50 value for Les-5581 was determined with intraperitoneal use and it was 510 mg/kg. Les-5581 exhibits significant anti-inflammatory activity at a dose of 50 mg/kg (intraperitoneal use) in an experiment on carrageenin- and formaldehyde-induced inflammatory models in white rats. The use of Les-5581 does not provoke a negative impact on the blood pattern, the liver enzymes function and has no ulcerogenic effect. Conclusions. The pyrazoline-thiazolidine- 4-one hybrid Les-5581 is a good molecular platform for development of new potential lowtoxicity anti-inflammatory drugs without ulcerogenic action. [ABSTRACT FROM AUTHOR]

A dry benzene solution of the Schiff base, N-(2-hydroxyphenyl)- 3‘-carboxy-2‘-hydroxybenzylideneimine upon reacting with mercaptoacetic acid undergoes cyclization and forms N-(2-hydroxyphenyl)-C-(3‘-carboxy-2‘- hydroxyphenyl) thiazolidin-4-one, LH3 (I). A MeOH solution of I reacts with CoII and CdII ions and forms the monomeric coordination compounds, [Co(LH)(MeOH)3](II) and [Cd(LH)(MeOH)](III). The coordination compounds have been characterized on the basis of elemental analyses, molar conductance, molecular weight, spectral (IR, reflectance, NMR) studies and magnetic susceptibility measurements. I behaves as a dibasic tridentate OOS donor ligand in these compounds. The compounds are nonelectrolytes (LM = 5.1-7.8 mho cm2 mol-1) in DMF. A tetrahedral structure for III and an octahedral structure for II are suggested. The ligand (I) and its coordination compounds shows antibacterial and antifungual activities towards bacteria, E. Coli. (Gram Negative) and S. Aureus (Gram Positive) as well as towards fungus, Candida Albicans. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Novel thiazolidin-4-one urea analogues were designed and synthesized. • 17b was identified as a FLT3/VEGFR2 dual inhibitor. • 17b induced cytotoxicity and suppression of migration, antiproliferation, apoptosis. Abstract A series of novel thiazolidine-4-one urea analogues were designed, synthesized and biologically evaluated. The structure-activity relationship (SAR) at several positions of the scaffolds was investigated and its binding mode was analyzed by molecular modeling studies. Compound 17b proved to be the most potent one, and IC 50 values against A549 and HT-29 cancer cell lines were 0.65 μM and 0.11 μM, respectively. The results of kinase profile demonstrated that compound 17b is a multikinase inhibitor that potently inhibits FLT3 (IC 50 = 8.6 nM) and VEGFR2 (IC 50 = 18.7 nM). The results of real-time live-cell imaging indicated that compound 17b showed excellent cytotoxicity and anti-proliferative activity against HT-29 cancer cells in a time- and dose-dependent manner, which was significantly potent than that of Cabozantinib. In addition, in vitro antitumor activity was associated with inducing cancer cell apoptosis and suppression of cancer cell migration. [ABSTRACT FROM AUTHOR]

In the centrosymmetric (racemic) title compound, chlorido­(3-cyclo­hexhyl-2-phenyl-1,3-thia­zolidin-4-one-κO)tri­phenyl­tin(IV), [Sn(C6H5)3Cl(C15H19NOS)], the tin(IV) atom exhibits a trigonal–bipyramidal coordination geometry with the three phenyl groups in equatorial positions and the chloride anion and ligand oxygen atom present at axial sites [O—Sn—Cl = 175.07 (14)°]. The thia­zolidinone ring of the ligand adopts an envelope conformation with the S atom as the flap. The dihedral angles between the heterocycle ring plane (all atoms) are 44.3 (9)° with respect to the pendant C-phenyl plane and 34.3 (11)° to the N-cyclo­hexyl ring (all atoms). The C-phenyl and N-cyclo­hexyl ring are close to orthogonal to each other, with a dihedral angle of 81.1 (4)° between them. In the crystal, mol­ecules are linked by weak C—H···Cl hydrogen bonds to generate [001] chains [ABSTRACT FROM AUTHOR]

Abstract: The three novel compounds of thiazolidin-4-one were synthesized by the reaction of essential oil of Anethum graveolens seeds (containing carvone) with thiosemicarbazide and acetylenic esters. The essential oil of A. graveolens seeds were analyzed by GC-MS after extraction that were containing high amount of carvone (37%). Carvonethiosemicarbazone was produced by the reaction of carvone with thiosemicarbazide that this compound in the reaction with acetylenic esters produced thiazolidin-4-one derivatives. The synthetic compounds 6a-c was confirmed by FT-IR, 1H-NMR, 13C-NMR and mass spectral data. Antimicrobial and antifungal activities of the synthetic compounds were assessed against 9 Gram-positive and 7 Gram-negative pathogenic bacteria as well as three fungal strains. The activities were reported as inhibition zone diameter, minimum inhibitory concentration, minimum bactericidal concentration and minimum fungicidal concentration values.Graphical abstract: [ABSTRACT FROM AUTHOR]

Hit, Lead & Candidate Discovery A series of 2‐(2‐substituted benzylidenehydrazinyl‐2‐oxopropyl)‐3‐(4‐[4‐oxo‐2‐phenylthiazolo din‐3‐yl]phenyl)quinazolin‐4(3H)‐one 7a‐7l were synthesized and characterized by IR, 1H‐NMR, 13C‐NMR, mass spectroscopy and elemental analyses. In this present study, the density functionality theory was performed to identify drug stability. Further we introduced graph theoretical analysis by utilised Kyoto Encyclopedia of Genes and Genomes (KEGG) database and Cytoscape software to identify drug target. Based on the observed drug target insilico modeling was executed to know effective drug. The antiepileptic effects of title compounds were evaluated by using MES and subcutaneous pentylenetetrazole (scPTZ) test. Acute neurological toxicity of title compounds was studied by using standardized rotorod test. After 0.5 hr of period many of the compounds showed anticonvulsant activity at MES or scPTZ test. Comparison of the biological activity of test compounds with its chemical structures indicates that, compounds possessing electron donating group exhibited superior activity than the analogs having electron withdrawing moieties. Among the electron donating group tested, amino derivative exhibited good activity than rest of derivatives. From the study it was concluded that, the compound 7j was established as very potent compared with rest of the compounds and standard drugs subjected to biological studies. Thus the compound 2‐(2‐[4‐aminobenzylidene]hydrazinyl‐2‐oxopropyl)‐3‐(4‐[4‐oxo‐2‐phenylthiazolidin‐3‐yl]phenyl) quinazolin‐4(3H)‐one (7j) came out as pilot derivative without any neurotoxicity with a wide spectrum of antiepileptic activity. Highlights: The performed work is having great significance in terms of Graph theoretical analysis used to identify drug targetIn silico modeling used to identify designed drug interaction with identify targetDensity functionality studies used to identify synthesized compound energy band gap which is correlate with enhancement of its biological activityAntiepileptic effects of entire synthesized quinazolinone scaffolds were evaluated by MES and scPTZ test2‐(2‐[4‐aminobenzylidene]hydrazinyl‐2‐oxopropyl)‐3‐(4‐[4‐oxo‐2‐phenylthiazolidin‐3‐yl]phenyl) quinazolin‐4(3H)‐one (7j) was established as very potent compared to the rest of the compounds and standard drugs which were subjected to biological studies [ABSTRACT FROM AUTHOR]

A series of 4-(2-(4-substituted phenyl)-4-oxoquinazolin-3(4H)-yl)-N-(2-(4 fluorophenyl)-4-oxo-5- (arylidene)thiazolidin-3-yl) benzamides (VIa-n) have been synthesized by condensation of N-(2-(4- fluorophenyl)-4-oxothiazolidin-3-yl)-4-(4-oxo-2-(4-substituted phenyl)quinazolin 3(4H)-yl)benzamides (Va-b) with various aryl/heteroaryl aldehydes using conventional methodology. All compounds were screened for their in vitro anticancer activity against the human breast cancer cell lines (MCF-7), human lung cancer cell lines (A549) using MTT assay method and doxorubicin is used as standard drug. Compound VId, VIk and VIn showed high potency against A549 cell lines with IC50 values 0.035±0.002 μM, 0.031±0.002 μM and 0.030±0.002 μM respectively compared to 0.023±0.002 μM showed by the standard. However, highest activity against MCF-7 cell lines was exhibited by Va, Vb, VIk and VIn with IC50 values between 0.040 - 0.050 μM. All the remaining compounds showed moderate anticancer activity against both the MCF-7 and A549 cell lines. To understand the interactions with active binding site of receptor, molecular docking study was also performed. [ABSTRACT FROM AUTHOR]

Abstract: Accessible chiral syntheses of 3 types of (R)‐2‐sulfanylcarboxylic esters and acids were performed: (R)‐2‐sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and acid (39%, 96%ee), (R)‐2‐sulfanylsucciinic diester (59%, 96%ee), and (R)‐2‐mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and robust method involves (i) clean SN2 displacement of methanesulfonates of (S)‐2‐hydroxyesters by using commercially available AcSK with tris(2‐[2‐methoxyethoxy])ethylamine and (ii) sufficiently mild deacetylation. The optical purity was determined by the corresponding (2R,5R)‐trans‐thiazolidin‐4‐one and (2S,5R)‐cis‐thiazolidin‐4‐one derivatives based on accurate high‐performance liquid chromatography analysis with high‐resolution efficiency. Compared with the reported method utilizing AcSCs (generated from AcSH and CsCO3), the present method has several advantages, that is, the use of odorless AcCOSK reagent, reasonable reaction velocity, isolation procedure, and accurate, reliable optical purity determination. The use of accessible AcSK has advantages because of easy‐to‐handle odorless and hygroscopic solid that can be used in a bench‐top procedure. The Ti(OiPr)4 catalyst promoted smooth trans‐cyclo‐condensation to afford (2R,5R)‐trans‐thiazolidin‐4‐one formation of (R)‐2‐sulfanylcarboxylic esters with available N‐(benzylidene)methylamine under neutral conditions without any racemization, whereas (2S,5R)‐cis‐thiazollidin‐4‐ones were obtained via cis‐cyclo‐condensation and no catalysts. Direct high‐performance liquid chromatography analysis of methyl (R)‐mandelate was also performed; however, the resolution efficiency was inferior to that of the thaizolidin‐4‐one derivatizations. [ABSTRACT FROM AUTHOR]

• Moiety was synthesized, characterized, and investigated by In-silico studies. • Crystal structure elucidation was done using single-crystal X-ray crystallography. • 2D fingerprint plots quantified all interactions via Hirshfeld surface analysis. • 3D energy framework calculations for intermolecular interaction energies were done. • Molecular docking and anti-lung cancer activity of synthesized compound were done. Ever since the disease of cancer was discovered, man has been mystified by both its mysterious origin and the even more mystifying mechanisms by which it spreads. Although advances in surgery and radiotherapy have significantly impacted cancer treatment, the idea of systemic chemotherapy which is targeted specifically at cancer cells and has minimal side effects remains a strategic goal for the future. A novel thiazolidin-4-one analogue was synthesized by the reaction of 1,2,4,5-tetraazaspiro[5.5]undecane-3-thione with chloroacetic acid. The newly synthesized compound was investigated theoretically as well as experimentally by FT-IR, 1H, 13C NMR and UV–Vis spectra and biologically screened in vitro for its anti-lung cancer activity against A549 cancer cell line. The crystal structure of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has been determined by single crystal X-ray diffraction and revealed that it belongs to monoclinic system with cell dimensions: a = 18.9393 (16) Å, b = 5.2747 (4) Å, c = 10.9518 (9) Å, α = 90°, β = 90.214 (3), γ = 90° and V = 1082.85 (15) Å3. Hirshfeld surface analysis was performed to study the nature of intermolecular interactions within the crystal structure via 3D and 2D fingerprint surfaces and to demonstrate H-bonding with close contacts in crystal via d norm surface. A descriptive study of (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one was done by using density functional theory at DFT/B3LYP/6–311 ++ G (d,p) basis set. Results of NLO analysis, ELF, LOL, NCI, AIM, HOMO-LUMO, first hyperpolarizability and molecular electrostatic potential were reported. Theoretical calculation of ADMET properties suggested that the synthesized compounds have a good pharmacokinetic profile. The results of cytotoxic evaluation indicated that (Z)-3-amino-2-(cyclohexylidenehydrazono)thiazolidin-4-one has broad-spectrum cytotoxic activity with IC 50 values of 240 μM against Human lung carcinoma cell line (A549). [Display omitted] [ABSTRACT FROM AUTHOR]

• The new HER2 inhibitors was synthesized with a thiazolidine-4-one structure. • Compound 7g is the most potent against MCF7 cells with IC 50 values 4.38 µM. • The selectivity of 7g is 9-fold higher than doxorubicin against MCF7 cells. • The in vitro tests were supported by in silico and 7g was found as the most active. In this study, 16 new hybrid compounds 6(a-h) and 7(a-h) were synthesized starting from methylparaben. These new compounds consist of eight 1,2,3-triazole-arylidenehydrazide derivatives and eight 1,2,3-triazole-thiazolidin-4-one derivatives. All compounds were tested against MCF-7 breast cancer cells and MCF10A breast healthy tissue to determine their anti-cancer activity. Molecular docking studies were also carried out against receptor proteins (HER2, EGFR, and VEGFR1) that are related to the growth factor of cancer cells to understand the inhibition mechanism. According to the results of in silico and in vitro activity studies, compounds 6g and 7g were found as the highest selective and active against breast cancer cells. The IC 50 values of compounds 6g and 7g against MCF7 cells were found as 8.48 and 4.38 µM, respectively. In addition, the IC 50 values of compounds 6g and 7g against MCF10A cells were found as 114.80 and 170.60 µM. When comparing the selectivity of the 6g and 7g to the reference drug doxorubicin, 6g and 7g had higher selectivity (13.5 and 39 respectively) compared to doxorubicin (4). The compound 7g also showed activity against cancer cells at lower doses and was found to be safe against healthy cells at high doses. Molecular docking results showed that both 6g and 7g had higher binding scores for all 3 target enzymes and especially for HER2 protein related to breast cancer with binding scores of -8.059 kcal and -9,008 kcal respectively, while doxorubicin had a binding score of -7.854 kcal. According to the results of the in vitro, and in silico study, compound 7g which was synthesized in this study is a promising, potent, and selective anti-cancer drug candidate for the treatment of breast cancer. All the tested compounds were very well characterized by spectroscopic methods and they have at least 95% HPLC purity. [Display omitted] [ABSTRACT FROM AUTHOR]

Thiazolidin-4-one derivative 3 was synthesized by the transformation of chloroacetamide derivative 2 with NH4SCN.The condensation of 3 with p-anisaldehyde afforded the corresponding arylidene derivative 4. Also, the alkylation of chloroacetamide derivative 2 with different heterocyclic compounds was investigated. Annulation of 5-amino-3-methylisoxazole ( 1) with α-halocarbonyl compounds 12 and 14 furnished pyrrolo[3,2-d]isoxazole and isoxazolo[5,4-b]azepin-6-one derivatives 13 and 15, respectively, while reaction of 1 with 1-chloro-4-(chloromethyl)benzene gave the monoalkylated product 17. The newly synthesized compounds were screened for their antitumor activity, and the geometry optimizations are in a good agreement with the experimentally observed data. [ABSTRACT FROM AUTHOR]

Both quinacrine, which contains a 9-aminoacridine scaffold, and thiazolidin-4-one are promising anticancer leads. In an attempt to develop effective and potentially safe anticancer agents, we synthesized 23 novel hybrid compounds by linking the main structural unit of the 9-aminoacridine ring with the thiazolidin-4-one ring system, followed by examination of their anticancer effects against three human breast tumor cell lines and matching non-cancer cells. Most of the hybrid compounds showed good activities, and many of them possessed the preferential killing property against cancer over non-cancer cells. In particular, 3-[3-(6-chloro-2-methoxy-acridin-9-ylamino)-propyl]-2-(2,6-difluoro-phenyl)-thiazolidin-4-one ( 11 ; VR118) effectively killed/inhibited proliferation of cancer cells at IC 50 values in the range of 1.2–2.4 μM. Furthermore, unlike quinacrine or cisplatin, compound 11 showed strong selectivity for cancer cell killing, as it could kill cancer cells 7.6-fold (MDA-MB231 vs MCF10A) to 14.7-fold (MCF7 vs MCF10A) more effectively than matching non-cancer cells. Data from flow cytometry, TUNEL and Western blot assays showed that compound 11 kills cancer cells by apoptosis through the down-regulation of Bcl-2 (but not Bcl-X L ) survival protein and up-regulation of Bad and Bax pro-apoptotic proteins. Thus, compound 11 is a highly promising lead for an effective and potentially anticancer therapy. [ABSTRACT FROM AUTHOR]

It was shown that 2-(1,3-thiazolidin-2-ylidene)acetamides can be used as 2-enamides in cyclocondensation reactions with oxalyl chloride, leading to the formation of new heterocyclic assemblies - 4-(4-oxo-1,3-thiazolidin-2-ylidene)pyrrolidine-2,3,5-triones in 50-88% yields. [ABSTRACT FROM AUTHOR]

In the title compound, C24H19N3O5S, the thiazole ring (r.m.s. deviation = 0.012 Å) displays a planar geometry and is surrounded by three fragments, two methoxyphenyl and one nitrophenyl. The thiazole ring is almost in the same plane as the nitrophenyl ring, making a dihedral angle of 20.92 (6)°. The two methoxyphenyl groups are perpendicular to the thiazole ring [dihedral angles of 79.29 (6) and 71.31 (7)° and make a dihedral angle of 68.59 (7)°. The molecule exists in an Z,Z conformation with respect to the C = N imine bond. In the crystal, a series of C--H...N, C--H...o and C--H...S hydrogen bonds, augmented by several π-π(ring) interactions, produce a three-dimensional architecture of molecules stacked along the b-axis direction. The experimentally derived structure is compered with that calculated theoretically using DFT(B3YLP) methods. [ABSTRACT FROM AUTHOR]

A series of reactions that result in the synthesis of novel thiazolidynones based on 4-chloro-3-nitrobenzopyran-2-one is presented in this study. During the condensation reaction of 4-chloro-3-nitrobenzopyran-2-one 2 and benzene-1,4-diamine, 4-(4-Amino-phenylamino)-3-nitro-chromen-2-one 3 is synthesized in high yield. By catalytic condensation of product 3 and benzaldehyde, salicylaldehyde and 3-nitrobenzaldehyde, novel derivatives of 4-[4-(Benzylideneamino)-phenylamino]-3-nitrobenzopyran-2-one, 4(a-c), as condensation products are synthesized. In the following series of reactions, by cyclization of the products 4(a-c) and 2-mercaptopropionic acid, corresponding substituted thiazolidinones 5(a-c) are synthesized. Determination of structure of the synthesized products is done on the basis of spectrometric data. Compounds 4(a-c) and 5(a-c) are examined for their antibacterial activity against S. aureus, E. coli and Klebsiella by measuring the zones of inhibition around the disks impregnated with the corresponding solutions of compounds in N,N-DMF concentration 2 mg/mL, 4 mg/mL and 6 mg/mL. Compounds of series 4 have shown moderate antibacterial activity against these microorganisms, whereas compounds of series 5 have shown significant activity. The impact of substitutions in antmicrobial activity is also explored. [ABSTRACT FROM AUTHOR]

• Two novel series of thiazolidin-4-one derivatives (9a–e and 10a–e) constituting ten compounds were synthesized under ultrasound irradiation. • The synthesized thiazolidin-4-one derivatives were evaluated for their in vitro cytotoxicity against the human esophageal cancer SKGT-4 cell line. • Thiazolidin-4-one derivatives 9e and 10b exerted the most potent cytotoxic activity. • The most active derivatives 9e and 10b were further evaluated for their apoptosis induction. • Molecular docking for the derivatives 9e and 10b was performed. In this work, two novel series of thiazolidin-4-one derivatives (9a–e and 10a–e) constituting ten compounds were synthesized under batch and ultrasound irradiation. It is found that the use of sonochemical methodology in the thiazolidin-4-ones synthesis offers several ecological advantages such as an effective, inexpensive, easy applicable, eco-friendly, and waste-free chemicals than the batch method. Different techniques including NMR (1H and 13C), mass spectra, and infrared radiation (FTIR) were employed to characterize the chemical structures of all the synthesized thiazolidin-4-one derivatives. The purified derivatives were tested for their anti-esophageal cancer activity against a panel of human esophageal cancer cell line (SKGT-4). The in vitro cytotoxic and apoptotic activities of these derivatives were evaluated by MTT and AO/EB assays, respectively. Among these derivatives, thiazolidin-4-one derivatives 9e and 10b were found to have the most potency toward SKGT-4 human esophageal cells. When compared to the reference standard (cisplatin, IC 50 5.21±0.41 µg/mL), the values (IC 50) of the derivatives 9e and 10b were found as 17.6 ± 0.06 and 18.5 ± 0.01 μg/mL, respectively. The collected data from AO/EB assay revealed these derivatives are able to stimulate the apoptotic effect in the SKGT-4 cells with a selective pathway compared to their behaviors in the normal Vero cells. Moreover, DFT-assisted calculations with theoretical level: B3LYP/6–31G(d,p) were adopted to optimize the geometrical structures of the derivatives 9e and 10b. To elucidate the possible binding mechanisms of these derivatives 9e and 10b with the active sites of human esophageal proteins (PDB ID: 6DUK , 2LEO , and 5HZN), the docking study was accomplished. According to the docking analysis, the derivatives 9e and 10b showed efficient interactions with the target receptors with low values of binding affinity. Thus, the biological tests and docking scores suggested that the synthesized thiazolidin-4-one derivatives 9e and 10b may be considered as a potential candidate for esophageal cancers treatments. [Display omitted] [ABSTRACT FROM AUTHOR]

Ammonium persulfate can be used as a homogeneous catalyst for three-component one-pot synthesis of some 1,3-thiazolidin-4-one derivatives from aldehydes, amines and mercaptoacetic acid under solvent-free conditions with good yields. The characterization of products was generally achieved by IR and NMR techniques. Inexpensive catalyst, high yields, simple product isolation and high atom economy are the noteworthy aspects of the protocols. [ABSTRACT FROM AUTHOR]

To develop novel antimycobacterial agents, a new series of thiazolidinone-azole hybrids 4a-b, 5a-b and 6-13 were designed and synthesized. Thiazolidin-4-ones (4a-b and 5a-b) were obtained by the reaction of Schiff bases and hydrazones (2a-b and 3a-b) with mercaptoacetic acid. 5-Benzylidene derivatives (6-13) were gained by treatment of 5a-b with appropriate benzaldehydes according to Knoevenagel condensation. To evaluate their structures ¹H NMR, IR, mass spectrometry and elemental analysis data were used. The target compounds were screened for their antimycobacterial activity against M. tuberculosis H37Rv strain using the microplate alamar blue assay method. Among them, 6, 10 and 12 (MIC: 14.27-14.74 µM) were found as most active compounds in the series. It was seen that both phenylamino and benzylidene substitutions on thiazolidin-4-one ring caused an improvement in the antimycobacterial activity. [ABSTRACT FROM AUTHOR]

Background The replacement of the thiazolidinedione moiety with a thiazolidinone may yield antidiabetic compounds with similar pleiotropic effects. Hence, the aim of the present study was to explore the dose-related antihyperglycemic and hypolipidemic effects of two synthesized novel thiazolidin-4-one derivatives, one with a nicotinamide and the other with a p-chlorophenoxyacetamide substitution at the N3 position of the thiazolidinone ring (NAT1 and PAT1, respectively), in a rodent model of metabolic syndrome (MetS). Methods Metabolic syndrome was induced in Wistar rats by neonatal administration of monosodium glutamate (i.p.) on 4 consecutive days followed by high-sucrose diet feeding for 6 months. The effects of NAT1 (33 and 66 mg/kg) and molar equivalent doses of PAT1 (40 and 80 mg/kg) on relevant biochemical parameters were evaluated. Because MetS is a state of chronic low-grade inflammation, we also evaluated the effects of these compounds on proinflammatory markers, namely interleukin (IL)-6, tumor necrosis factor (TNF)-α, reactive oxygen species (ROS), and nitric oxide (NO). Results Both NAT1 and PAT1 attenuated hyperglycemia, hypertriglyceridemia, hypoalphalipoproteinemia, and glucose intolerance. PAT1 exhibited superior antihyperglycemic and antihypoalphalipoproteinemic effects than NAT1. However, NAT1 had a better triglyceride-lowering effect. At the lower dose tested, both compounds significantly reduced elevated malondialdehyde levels. In addition, PAT1 (80 mg/kg) restored hepatic superoxide dismutase enzyme levels. There was a tendency for NAT1 and PAT1 to inhibit elevated hepatic IL-6 and TNF-α levels, but the differences did not reach statistical significance. In addition, PAT1 exhibited in vitro anti-inflammatory activity by reducing proinflammatory ROS and NO levels in RAW264.7 macrophages. Conclusions The novel thiazolidin-4-ones NAT1 and PAT1 could be potential pleiotropic drug candidates targeting MetS. [ABSTRACT FROM AUTHOR]

The title compound (Z)-5-(4-chlorobenzylidene)-3-(2-ethoxyphenyl)-2-thioxothiazolidin-4-one (CBBTZ) was characterized by X-ray single crystal diffraction, 1H NMR and 13C NMR spectra. Theoretical investigations were carried out using HF and DFT levels of theory at 6-31G(d,p) basis set. The X-ray structure is compared with that computed. The calculated geometrical parameters are in good agreement with those determined by X-ray diffraction. The dihedral angle between the two benzene rings is 16.89(5)° indicating that the structure is non planar. The molecule exhibits intraand intermolecular contacts of type C–H···O, C–H···S and C–H···Cl. The intercontacts in the crystal structure are explored using Hirshfeld surfaces analysis method. [ABSTRACT FROM AUTHOR]

The promising role of thiazolidin-4-ones (TZOs) against inflammatory conditions has been reported. From our lab, one of the TZO derivatives, compound 4C, exerted anti-inflammatory potential via inhibition of locally released cytokines and prostaglandin. In continuance, a detailed study was undertaken for the preclinical profiling of this promising TZO derivative against polyarthritis in rats, along with assessment of risk associated with the treatment. Male Sprague-Dawley rats were used for the adjuvant-induced arthritis (AIA) model. Based on the development of secondary lesion, the animals were randomized into different treatment groups. To establish the efficacy of the test compound, parameters such as inflammation, pain, disease progression, cytokines and prostaglandin (PG)-E 2 levels and complete blood cell profile were recorded along with radiological and histological examinations of joints. The study also focused on evaluating the side effect of test compound on gastric, liver, renal, blood and cardiovascular components. Compound 4C exerted promising therapeutic effect against secondary lesions in polyarthritis in rats. It limited the progression of chronic inflammation and associated pain in rats. Modulation of cytokine signalling and arachidonate metabolism by 4C was evident from inhibition of interleukin (IL)-6, tumor necrosis factor (TNF)-α and PGE 2 generation in AIA rats. Comparatively, compound 4C was safer than diclofenac to cause gastric, liver, renal, blood and cardiovascular toxicities. These finding supports the efficacy and safety profile of 4C, a TZO derivative in limiting the progression of arthritis when administered orally. [ABSTRACT FROM AUTHOR]

Novel seven-membered iminosugars fused thiazolidin-4-one and benzthiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. Benzoyl group (Bz) migrations were found in the synthesis of 8c and 9b using D-galactoside or D-mannoside as starting materials, respectively, which was suggested by HMBC and X-ray. The new bi/tricyclic iminosugars 3~4 ( a–d ) and 5 ( b–d ) were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that all compounds except 5b could effectively inhibit RT activity. Among them, compounds 3c and 4c were the best ones with the IC 50 values of RT inhibitory activities of 2.11 µM and 2.73 µM, respectively. Structure–activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was beneficial for their anti-HIV RT activity. [ABSTRACT FROM AUTHOR]

A simple, efficient, and eco-friendly procedure for the synthesis of thiazolidin-4-one derivatives in water from cyclocondensation reaction of thiosemicarbazone derivatives and dimethylacetylene dicarboxylate (DMAD) in good yield is reported. The regiochemistry of the cyclized products is established by elemental analysis, IR, NMR, and mass spectral data. A single crystal X-ray diffraction study of a representative compound,3f, is reported. [ABSTRACT FROM PUBLISHER]

Barium molybdate (BaMoO4) nanopowder was successfully synthesizedviaa simple precipitation route without any surfactant. The prepared nanopowder was applied for the facile synthesis of 2,3-diarylthiazolidin-4-one derivatives using cyclization reaction of aromatic aldehydes, aromatic amines, and thioglycolic acid under ambient condition. [ABSTRACT FROM PUBLISHER]

An eco-friendly procedure for synthesis of 2-(2-oxo-2H-chromen-4-yl)-3-arylthiazolidin-4-one derivatives by three-component reaction of 2-oxo-2H-chromene-4-carbaldehydes, aromatic amines and thioglycolic acid, with tetramethylbutane-1,4-diammonium acetate as a low-cost ionic liquid catalyst under reflux condition is described. The use of an ionic liquid as a catalyst has the advantages of high yields, short reaction time and environmentally friendly reaction media. [ABSTRACT FROM PUBLISHER]