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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]

In this study, we synthesized 5-alkyl/arylidene-2-(morpholin/thiomorpholin-4-yl)-1,3-thiazol-4(5H)-one through a one-pot reaction using all starting materials in a microwave oven. The presence of the solid base MgO catalyzed the reaction in the eco-friendly solvent of ethanol as a green chemistry approach owing to the noticeable advantages of short reaction times to save energy and less toxic starting materials for environmental friendliness. This indicates that the one-pot reaction makes the process simpler, in which the reaction time (1 h) is shorter than that of conventional methods (10 h). The yield of the reactions reached 55–76% for 18 final products consisting of 17 derivatives of morpholine or thiomorpholine with various aldehydes and one extended moiety of the primary amine, of which 13/18 final compounds were new. The purification procedure was performed without using polluting solvents. The structures were confirmed using IR, 1H-NMR, 13C-NMR, and MS analyses.

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]

Cancer is one of the life-threatening diseases accountable for millions of demises globally. The inadequate effectiveness of the existing chemotherapy and its harmful effects has resulted in the necessity of developing innovative anticancer agents. Thiazolidin-4-one scaffold is among the most important chemical skeletons that illustrate anticancer activity. Thiazolidin-4-one derivatives have been the subject of extensive research and current scientific literature reveals that these compounds have shown significant anticancer activities. This manuscript is an earnest attempt to review novel thiazolidin-4-one derivatives demonstrating considerable potential as anticancer agents along with a brief discussion of medicinal chemistry-related aspects of these compounds and structural activity relationship studies in order to develop possible multi-target enzyme inhibitors. Most recently, various synthetic strategies have been developed by researchers to get various thiazolidin-4-one derivatives. In this review, the authors highlight the various synthetic, green, and nanomaterial-based synthesis routes of thiazolidin-4-ones as well as their role in anticancer activity by inhibition of various enzymes and cell lines. The detailed description of the existing modern standards in the field presented in this article may be interesting and beneficial to the scientists for further exploration of these heterocyclic compounds as possible anticancer agents. [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]

Abstract 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.

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]

ABSTRACTThe 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.

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]

Here we report the application of a multi-disciplinary protocol for investigating thiazolidin-4-one-based compounds as new promising anti-inflammatory agents interfering with the eicosanoid biosynthesis pathways. The workflow foresaw the generation of a focused virtual library of ∼4.2 ​× ​104 molecules featuring the thiazolidin-4-one core based on the related one-pot synthetical combinatorial route. The built library was initially screened in silico against the microsomal prostaglandin E2 synthase-1 (mPGES-1) enzyme and, afterwards, 23 selected chemical items were synthesized for the subsequent biological screening, applying the one-pot multicomponent synthetic strategy. Preliminary results highlighted the moderate ability of several tested thiazolidin-4-one-based compounds in inhibiting mPGES-1. On the other hand, further computational repurposing investigations were performed on a set of synthesized compounds, highlighting the promising binding of a several items against the soluble epoxide hydrolase (sEH) enzyme, whose inhibition leads to an increase of epoxyeicosatrienoic acids (EETs) that are anti-inflammatory mediators. Three molecules (3, 9 and 21) were able to inhibit sEH featuring IC50 values in the low micromolar range. In order to further profile their anti-inflammatory properties, additional investigations of the three identified hits highlighted their ability to inhibit 5-lipoxygenase (5-LO) and thus to interfere with leukotriene biosynthesis in neutrophils, devoid of activity against cyclooxygenases (COXs) and cytotoxic effects on human monocytes. Our results, obtained by applying a multidisciplinary approach, highlight the thiazolidin-4-one-core as a valuable template for developing novel anti-inflammatory compounds able to synergistically inhibit different targets involved in the arachidonic acid cascade.

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.

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]

Abstract Background Tuberculosis is evidently a major health threat among human populations worldwide. The current study presents the synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs (4a–o) as potential Mycobacterium tuberculosis DNA gyrase inhibitors. DNA gyrase regulates DNA topology in MTB and has been a target of choice for antibacterial therapy. With this in mind, the synthesized derivatives (4a–o) were subjected to in vitro antitubercular evaluation by the MABA method and were tested for MTB DNA gyrase inhibition by supercoiling assay. Results All the synthesized compounds displayed inhibition of MTB within the MIC range of 1.56–12.5 μM. Further, out of the selected compounds that underwent DNA gyrase inhibition, compound 4o proved to be a potent lead molecule by displaying 82% of enzyme inhibition at 1 μM. All the synthesized derivatives also underwent molecular docking studies to comprehend their hypothetical binding interactions with Mycobacterium smegmatis GyrB. Conclusion All the results suggested that most of the synthesized derivatives inhibited Mycobacterium tuberculosis, and some 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs could act as leads for the development of antitubercular agents.

Abstract The first report about antimicrobial resistance was published in the 1940s. And today, the antimicrobial resistance has become a worldwide problem. Because of this problem, there is a need to develop new drugs. That’s why we synthesized some novel thiazolidine-4-one derivatives and evaluated their antimicrobial activity. The final compounds were obtained by reacting 2-[(4,5-diphenylthiazol-2-yl)imino]thiazolidin-4-one with some aryl aldehydes. The synthesized compounds were investigated for their antimicrobial activity against four Candida species, five gram-negative and four gram-positive bacterial species. The lead compounds (4a- h) were obtained with a yield of at least 70%. All compounds showed antimicrobial activity. Compound 4f (MIC: 31.25 µg/ml) exhibited more efficacy than the other compounds against C. glabrata (ATCC 24433). Compound 4b (MIC: 62.5 µg/ml) was the most active compound against all bacterial species, particularly K. pneumoniae (NCTC 9633). Whereas, compound 4c (MIC:

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]

New sets of functionalized thiazolidinone and thiadiazole derivatives were synthesized, and their cytotoxicity was evaluated on HepG2, MCF-7, HTC-116, and WI38 cells. The synthetic approach is based on the preparation of 4-(4-acetamidophenyl)thiosemicarbazide (4) and their thiosemicarbazones 5 a-e, which are converted to the corresponding thiazoldin-4-one compounds 6 a-e upon cyclization with ethyl bromoacetate. The thiadiazole compounds 9 and 12 were obtained by reacting 4-(4-acetamidophenyl)thiosemicarbazide with isothiocyanates and/or ethyl 2-cyano-3,3-bis(methylthio)acrylate, respectively. The thiazolidinone compounds 6 c and 6 e exhibited strong cytotoxicity against breast cancer cells, with an IC 50 (6.70±0.5 μM) and IC 50 (7.51±0.8 μM), respectively, very close to that of doxorubicin (IC 50 : 4.17±0.2 μM). In addition, the anti-cancer properties of the tested thiazolidinone and thiadiazole scaffolds were further explored by the molecular docking program (MOE)-(PDB Code-1DLS). Compounds 5 d, 5 e, 6 d, 6 e, and 7 have the best binding affinity, ranging from -8.5386 kcal.mol -1 to -8.2830 kcal.mol -1 ., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

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]

Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a DNA repair enzyme that plays a key role in repairing damage caused by various antitumor drugs. It is a promising target in medicinal chemistry for the creation of cancer adjuvant therapy. Inhibition of this enzyme together with the use of anticancer chemotherapy enhances the effect of the latter. The natural mutant of TDP1, TDP1(H493R), causes severe neurodegenerative disease spinocerebellar ataxia syndrome with axonal neuropathy (SCAN1). Inhibition of TDP1(H493R) appears to be useful in containment the progression of the disease. A library of compounds was synthesized starting from dehydroabietylamine including heterocyclic pharmacophore groups in the core. To obtain the desired products, the starting dehydroabietylamine was introduced sequentially in reaction with isothiocyanate and ethyl bromoacetate. Different classes of heterocyclic derivatives—2-iminothiazolidin-4-ons and 2-thioxoimidazolidin-4-ones—were obtained depending on the addition order of reagents. 2-Iminothiazolidin-4-thiones were obtained from 2-iminothiazolidin-4-ones under the action of the Lawesson's reagent. Effective TDP1 inhibitors were found among the obtained compounds that work in submicromolar concentrations. The inhibitor of TDP1(H493R) was also detected. [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.

Background and Aim: In an effort of drug development in the area of HIV, present work deals with development of 2D and 3D QSAR of thiazolidinone derivatives against HIV-RT activity as a powerful method for elucidation the relationships between structure and activity. Materials and Methods: 2D QSAR and 3D QSAR were performed using MLR and SA kNN method respectively. Models which had higher predictability were generated as indicated from their statistical parameters. Results and Discussion: Best models generated showed correlation coefficient r²= 0.9256 and q² =0.8623 for 2D QSAR and q² =0.8444 for 3D QSAR. The models indicated the requirement of electro topological, electrostatic and steric descriptors which would significantly contribute to HIV-RT inhibitory activity. Further a few compounds were designed using the outcome of QSAR studies. [ABSTRACT FROM AUTHOR]

In recent years for the development of novel anticancer hybrids with two or more pharmacophores of bioactive scaffolds to produce a single molecule by blending or linking has emerged as a simple strategy by providing an effective control on malignant process with improved biological potential. In this view, Sesamol being an active scaffold with important biological activities was modified and linked with various substitutions to afford thiazolidin-4-one derivatives. Herein, we report the synthesis, characterization of around twenty one compounds and their evaluation for antioxidant and anticancer potentials. The structures of these compounds were established by IR, 1H NMR, 13C NMR, and Mass. The compounds 1–15 were evaluated for in vitro cytotoxicity against three human lung cancer cell lines (A549, MCF-7 and HeLa), respectively. In preliminary MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] cytotoxicity studies compounds 9 and 12 were found most effective. In A549 cancer cells the CTC50 (50% of cytotoxicity inhibition) were observed at 84.27 ± 2.7 & 91.98 ± 4.2 µg/ml, respectively. Moreover, in MCF-7 and HeLa cells the CTC50 values were observed at 174.3 ± 4 4.1, 69.15 ± 3.4 and 42.90 ± 3.5, 180.77 ± 4.6 µg/ml, respectively. Compounds 9 and 12 also exhibited best DNA damage activity via cell apoptosis when screened against Human breast cancer cell lines A549 and MCF-7 when compared to standard doxorubicin. In this study, Compounds 1, 9, 11 and 12 (at concentration 100 mg/kg/body wt.) were selected for in vivo anticancer activity against Dalton’s Lymphoma Ascites bearing mice. Among the tested compounds all has shown modest antitumor activity and merited anti-cancer activity due to its cytotoxic properties when compared with standard methotrexate.

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]

A library of pyran-2H-one-3-ylmethylidene and chromene-2H-one-3-ylmethylidene derivatives of the titled heterocyclic framework was synthesized from 3-acyl-4-hydroxypyran/chromene-2H-one via sequential reaction with thiosemicarbazide and dialkyl acetylenedicarboxylates. The syntheses were carried out under efficient catalysis of a new binary ionic liquid mixture [l-prolinium chloride][1-methylimidazolium-3-sulfonate] in one pot and solvent-free conditions. Calculations based on density functional theory displayed that the barrier energy for interconversion of the two possible diastereomeric isomers of each product is less than the thermal energy of molecules at room temperature, as only one product can be resolved from a given reaction mixture. This seems to be the case for the previously reported hydrazonothiazolidines. The binary ionic liquid mixture melts at near room temperature and can be considered as a solution of HCl in 1:1 mixture of two zwitterionic species. It proved to be more efficient than its constituents in catalyzing the above synthesis in one-pot operation. Some of the synthesized products have shown pronounced antibacterial activities. The ionic liquid is virtually stable in air and moisture, as can be retrieved several times without appreciable decrease in its catalytic activity. [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 new methyl [3-(4-chlorophenyl)-2-{[(2,4-dichloro-1,3-thiazol-5-yl)methylidene]hydrazinylidene}-4-oxo-1,3-thiazolidin-5-ylidene]acetate was synthesized from 4-(4-chlorophenyl)-1-(2,4-dichloro-1,3-thiazol-5-yl)methylidene-3-thiosemicarbazide using dimethyl acetylenedicarboxylate as thia-Michael reaction acceptor. New compounds (3 and 4) were characterized by IR, 1H and 13C NMR spectroscopy methods.

The present study deals with the synthesis, spectroscopic characterization, antibacterial and antifungal activities of novel series five-membered ring heterocyclic compounds containing nitrogen and sulfur heteroatoms. The synthetic routes have been divided into two parts: The first one includes synthesis of compounds (4a-c) through one pot operation three component reaction of 2-naphthol (1), substituted benzaldehyde (2a-c) and thiourea (3) in 1,2-dichloromethane, using a catalytic amount of ZrOCl2.8H2O and compound (6) was synthesized using semicarbazide (5) in absolute ethanol and indium (III) chloride as catalyst. The second part is the hetero-cyclization reactions of the compounds (4a-c and 6) to obtain the heterocyclic compounds (7a-c, 8, and 9). The structures of the synthesized products are verified on the basis of (FT-IR, 1H-NMR and 13C-NMR) spectroscopy. The synthesized compounds antibacterial activities were screened against Staphylococcus aureus (Gram positive) and Escherichia coli (Gram negative) bacteria as compared to standard amikacin and antifungal activity against Candida albicans fungi as compared to standard Nystatin, well diffusion method is used. The antibacterial and antifungal activities of synthesized compounds (7a-c, 8 and 9) were higher than the antibacterial and antifungal activities of synthesized compounds (4a-c and 6).

The crystal structures of two closely related compounds, 1-cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one, C15H18N2O3S, (1) and 1-cyclohexyl-2-(2-nitrophenyl)-1,3-thiazolidin-4-one 1,1-dioxide, C15H18N2O5S, (2), are presented. These compounds are comprised of three types of rings: thiazolidinone, nitrophenyl and cyclohexyl. In both structures, the rings are close to mutually perpendicular, with interplanar dihedral angles greater than 80° in each case. The thiazolidinone rings in both structures exhibit envelope puckering with the S atom as flap and the cyclohexyl rings are in their expected chair conformations. The two structures superpose fairly well, except for the orientation of the nitro groups with respect to their host phenyl ring, with a difference of about 10° between 1 and 2. The extended structure of 1 has two kinds of weak C—H...O interactions, giving rise to a closed ring formation involving three symmetry-related molecules. Structure 2 has four C—H...O interactions, two of which are exclusively between symmetry-related thiazolidinone dioxide moieties and have a parallel `give-and-take-fashion' counterpart. In the other two interactions, the nitrophenyl ring and the cyclohexane ring each offer an H atom to the two O atoms on the sulfone group. Additionally, a C—H...π interaction between a C—H group of the cyclohexane ring and the nitrophenyl ring of an adjacent molecule helps to consolidate the structure.

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]

The crystal structures of two (oxothiazolidin-2-ylidene)acetamides, namely (Z)-2-[2-(morpholin-4-yl)-2-oxoethylidene]thiazolidin-4-one, C9H12N2O3S, (I), and (Z)-N-(4-methoxyphenyl)-2-(4-oxothiazolidin-2-ylidene)acetamide, C12H12N2O3S, (II), are described and compared with a related structure. The Z conformation was observed for both the compounds. In (I), the morpholin-4-yl ring has a chair conformation and its mean plane is inclined to the thiazolidine ring mean plane by 37.12 (12)°. In (II), the benzene ring is inclined to the mean plane of the thiazolidine ring by 20.34 (14)°. In the crystal of (I), molecules are linked by N—H...O hydrogen bonds, forming C(6) chains along the b-axis direction. The edge-to-edge arrangement of the molecules results in short C—H...O and C—H...S interactions, which consolidate the chain into a ribbon-like structure. In the crystal of (II), two N—H...O hydrogen bonds result in the formation of C(8) chains along the b-axis direction and C(6) chains along the c-axis direction. The combination of these interactions leads to the formation of layers parallel to the bc plane, enclosing R44(28) rings involving four molecules.

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.

Mycobacteria regulate the synthesis of mycolic acid through the fatty acid synthase system type 1 (FAS I) and the fatty acid synthase system type-2 (FAS-II). Because mammalian cells exclusively utilize the FAS-I enzyme system for fatty acid production, targeting the FAS-II enzyme system could serve as a specific approach for developing selective antimycobacterial drugs. Enoyl-acyl carrier protein reductase enzyme ( Mt InhA), part of the FAS-II enzyme system, contains the NADH cofactor in its active site and reduces the intermediate. Molecular docking studies were performed on an in-house database (∼2200 compounds). For this study, five different crystal structures of MtInhA (PDB Code: 4TZK, 4BQP, 4D0S, 4BGE, 4BII) were used due to rotamer difference, mutation and the presence of cofactors. Molecular dynamics simulations (250 ns) were performed for the novel 2-acylhydrazono-5-arylmethylene-4-thiazolidinones derivatives selected by molecular docking studies. Twenty-three compounds selected by in silico methods were synthesized. Antitubercular activity and Mt InhA enzyme inhibition studies were performed for compounds whose structures were elucidated by IR, 1 H-NMR, 13 C-NMR, HSQC, HMBC, MS and elemental analysis.Communicated by Ramaswamy H. Sarma.

In this study, novel 3-(phenylamino)thiazolidin-4-one 2 a-d and 3-(phenyl)thiazolidin-4-one 3 a-g derivatives which are having benzimidazole moiety were synthesized and their tyrosinase inhibitory activity were investigated. The structures of the target compounds were elucidated using 1 H/ 13 C-NMR, IR and MS. The structure of 2 b was also characterized using HSQC NMR technique. Among the target compounds, 3 b-g demonstrated stronger tyrosinase inhibitory activity (IC 50 values for 3 b-g ranged from 80.93 to 119.20 μM), compared to the positive control kojic acid (IC 50 : 125.08 μM). With IC 50 value of 80.93 μM, 5-(2-(4-(1H-benzimidazol-1-yl)phenyl)-4-oxothiazolidin-3-yl)-2-methylbenzenesulfonamide 3 g was found to be the most active derivative of the series. Molecular docking studies were conducted to elucidate the binding interactions between compounds and tyrosinase. The MTT assay studies used to determine the cytotoxicity of 3 b-g showed that 3 c, 3 d, 3 f and 3 g were not cytotoxic in the range of 0-200 μM. Considering its tyrosinase inhibitory activity and cytotoxic effect, 3 g exhibits promising potential for further research and development as a novel tyrosinase inhibitor., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

The present study aims to examine the structural requirements governing α-amylase inhibitory activity of 5-(3-arylallylidene)-2-(arylimino)thiazolidin-4-one derivatives and their precursors by employing a multifaceted approach combining in vitro and in silico studies. The in vitro assay findings revealed strong inhibitory effect of this class of compounds against α-amylase and compound 20 exhibited maximum percentage inhibition of 88.54 ± 0.69, 84.98 ± 0.40, 77.26 ± 0.75, 67.80 ± 0.54, and 62.93 ± 1.17 at 200, 100, 50, 25, and 12.5 µg mL -1 , respectively. Multiple CORAL QSAR models were developed from the randomly distributed eight splits by employing two target functions (TF 1 , TF 2 with W CII = 0.0 and = 0.3, respectively), and the quality of predictions by the produced models was validated with the help of various statistical parameters. The model M-4 ( R 2 Val = 0.8799 ) and model M-11 ( R 2 Val = 0.9064 ) were the leading models developed by using TF 1 and TF 2 . We designed five new congeneric inhibitors (D-1 to D-5) by incorporating SMILES features positively correlating with the activity. Molecular docking experiments were carried out to confirm the binding of these new inhibitors with the biological receptor α-amylase ( PDB ID: 7TAA ). Furthermore, molecular dynamic simulations provided a thorough knowledge of the binding process by shedding insight into the dynamic behavior and stability of the ligand-receptor complex over time. The results of this study highlight the key structural characteristics needed for improved α-amylase inhibitory efficacy and provide a rational basis for the development of more effective inhibitors.Communicated by Ramaswamy H. Sarma.