141-84-4Relevant articles and documents
Systems biology approaches based discovery of a small molecule inhibitor targeting both c-Met/PARP-1 and inducing cell death in breast cancer
Chen, Jie,Cheng, Lijia,Dong, Hongbo,He, Gang,Shi, Zheng,Tang, Yong,Xiong, Hang,Xu, Guangya,Yan, Xueling,Yu, Tian,Zhou, Hui
, p. 2656 - 2666 (2020)
Breast cancer is the second most common types of cancer worldwide. Molecular strategies have developed rapidly; however, novel treatments strategies with high efficacy and lower toxicity are still urgently demanded. Notably, biological networks estimated from microarray data and functional activity network analysis could be utilized to identify and validate potential targets. In this study, two microarray data (GSE13477, GSE31192) were firstly selected, and analyzed by multi-functional activity network analysis to generate the core protein-protein-interaction (PPI) network. Several potential targets were subsequently identified and c-Met and poly (ADP-ribose) polymerase-1 (PARP-1) were manually chosen as the key targets in breast cancer. Furthermore, virtual screening and molecular dynamics (MD) simulations were utilized to recognize novel c-Met/PARP-1 inhibitors in Specs products database. Three small molecules, namely, ZINC19909930, ZINC20032678 and ZINC13562414 were selected. Additionally, these compounds were synthesized, and two breast cancer cell lines, MDA-MB-231 and MCF-7 cells were used to validate our bioinformatic findings in vitro. MTT assay and Hoechst staining showed that ZINC20032678 significantly induced breast cancer cell death, which was mediated through apoptosis by flow cytometry. Furthermore, ZINC20032678 was shown to target the active sites of the both targets and recruitment of downstream apoptotic signaling pathways, eventually inducing breast cancer cell apoptosis. Collectively, our findings not only offer systems biology approaches based drug target identification, but also provide the new clues for developing novel inhibitors for future breast cancer research.
Comparative study of the structure of rhodanine, isorhodanine, thiazolidine-2,4-dione, and thiorhodanine
Enchev,Chorbadjiev,Jordanov
, p. 1110 - 1120 (2002)
Ab initio (HF and MP2 level) and semiempirical (AM1, PM3, MNDO) calculations on the relative stabilities and structures of the potential tautomeric forms of rhodanine, isorhodanine, thiazolidine-2,4-dione, and thiorhodanine are reported. Ab initio calculations predict that the thiooxo, oxothio, dioxo, and dithio tautomers are the most stable. These results correspond to the known experimental data. Infrared spectra of the investigated compounds were recorded for the region 4000-150 cm-1, and the characteristic bands were compared with ab initio calculated frequencies at the HF/3-21G(*)* level.
A New Synthesis Strategy for Rhodanine and Its Derivatives
Pan, Zhenliang,An, Wankai,Wu, Lulu,Fan, Liangxin,Yang, Guoyu,Xu, Cuilian
, p. 1131 - 1134 (2021/05/25)
Rhodanine and its derivatives have been known as privileged structures in pharmacological research because of their wide spectrum of biological activities, but the synthesis method of rhodanine skeleton is limited. In this paper, not only rhodanine skeleton, but also N -aryl rhodanines can be directly prepared via the reaction of thioureas and thioglycolic acid in one step catalyzed by protic acid, which provides a new approach of the synthesis of rhodanine and its derivatives. The developed strategy is straightforward, efficient, atom economical, and convenient in good yields.
Synthesis, characterization, antibacterial and antioxidant potency of nsubstituted- 2-sulfanylidene-1,3-thiazolidin-4-one derivatives and QSAR study
Brahmbhatt, Harshad,Molnar, Maja,Pavi?, Valentina,Rastija, Vesna
, p. 840 - 849 (2020/01/25)
Background: Rhodanine is known for its potential and important role in the medicinal chemistry since its derivatives exhibit a wide range of pharmacological activities such as antibacterial, antifungal, antidiabetic, antitubercular, anti-HIV, antiparasitic, antioxidant, anticancer, antiproliferative and anthelmintic agents. Objectives: Since N-substituted rhodanine synthons are rarely commercially available, it is desirable to develop a straightforward synthetic approach for the synthesis of these key building blocks. The objective was to synthesize a series of rhodanine derivatives and to investigate their antimicrobial and antioxidant activity. Also, in order to obtain an insight into their structure-activity relationship, QSAR studies on the antioxidant activity were performed. Methods: 1H and 13C FTNMR spectra were recorded on Bruker Avance 600 MHz NMR Spectrometer, mass analysis was carried out on ESI+ mode by LC-MS/MS API 2000. 2,2-Diphenyl-1- picrylhydrazyl radical scavenging activity (% DPPH) was determined in dimethylsulfoxide (DMSO) as a solvent. The antibacterial activity was assessed against Bacillus subtilis, Staphylococcus aureus (Gram positive) and Escherichia coli, Pseudomonas aeruginosa (Gram negative) bacteria in terms of the minimum inhibitory concentrations (MICs) by a modified broth microdilution method. Results: A series of N-substituted-2-sulfanylidene-1,3-thiazolidin-4-ones were synthesized and characterized by 1H NMR, 13C NMR, FTIR, GC MS, LCMS/MS and C,H,N,S elemental analysis. Most of the synthesized compounds showed moderate to excellent antibacterial activity (MIC values from 125 μg/ml to 15.62 μg/mL) and DPPH scavenging activity (from 3.60% to 94.40%). Compound 2-thioxo-3- (4-(trifluoromethyl)-phenyl)thiazolidin-4-one showed the most potent activity against Escherichia coli (3.125 μg/mL), equivalent to antibiotic Amikacin sulphate and against Staphylococcus aureus (0.097 μg/ml), 100 times superior then antibiotic Amikacin sulphate. It has also shown a potent antioxidant activity (95% DPPH scavenging). Two best QSAR models, obtained by GETAWAY descriptor R7p+, Balabans molecular connectivity topological index and Narumi harmonic topological index (HNar), suggest that the enhanced antioxidant activity is related to the presence of pairs of atoms higher polarizability at the topological distance 7, substituted benzene ring and longer saturated aliphatic chain in N-substituents. Conclusion: A series of novel N-substituted-2-thioxothiazolidin-4-one derivatives were designed, synthesized, characterized and evaluated for their antibacterial and antioxidant activity in vitro. Majority of the compounds showed excellent antibacterial activity compared to ampicillin and few of them have an excellent activity as compared to Chloramphenicol standard antibacterial drug. The QSAR study has clarified the importance of presenting a pairs of atoms higher polarizability, such as Cl and S at the specific distance, as well as the substituted benzene ring and a long saturated aliphatic chain in N-substituents for the enhanced antioxidant activity of 2-sulfanylidene-1,3- thiazolidin-4-one derivatives.
Highly efficient microwave synthesis of rhodanine and 2-thiohydantoin derivatives and determination of relationships between their chemical structures and antibacterial activity
Tejchman, Waldemar,Orwat, Bartosz,Korona-G?owniak, Izabela,Barbasz, Anna,Kownacki, Ireneusz,Latacz, Gniewomir,Handzlik, Jadwiga,?es?awska, Ewa,Malm, Anna
, p. 39367 - 39380 (2019/12/14)
Here we report studies on the synthesis of 12 new heterocyclic derivatives that differ in three structural motifs and the simultaneous evaluation of the impact of these three variables on the biological properties. The examined compounds are based on rhodanine and 2-thiohydantoin cores equipped with hydrogen or carboxymethyl substituents at the N-3 position and linked to a triphenylamine moiety through 1,4-phenylene, 1,4-naphthalenylene and 1,9-anthracenylene spacers at the C-5 position of the heterocycles. All the compounds were synthesized very quickly, selectively and in high yields according to the developed microwave-assisted Knoevenagel condensation protocol, and they were characterized thoroughly with NMR, FT-IR and ESI-HRMS techniques. The derivatives were tested for their activity against selected strains of Gram-positive and Gram-negative bacteria and yeast. Two compounds showed good activity against Gram-positive bacteria, and all of them showed low cytotoxicity against three cell lines of the human immune system. Based on membrane permeability assays it was demonstrated that the active compounds do not penetrate the cell membrane, and thus they must act on the bacterial cell surface. Finally, we proved that the evaluated structure modifications had a synergistic effect and the simultaneous presence of a 1,4-phenylene spacer and carboxymethyl group at N-3 caused the highest boost in antimicrobial activity.
2-thiothiazolidine-4-one, derivative and preparation method thereof
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Paragraph 0049; 0051; 0056; 0061, (2018/11/03)
The invention provides 2-thiothiazolidine-4-one, a derivative and preparation method thereof. Mercaptoacetic acid and thiourea are heated to synthesize 2-thiothiazolidine-4-one by taking 95% concentrated sulfuric acid as a catalyst. Under catalysis of active copper, 2-thiothiazolidine-4-one and halohydrocarbon are subjected to thin-layer chromatographic monitoring reaction through microwave irradiation by taking water as a solvent; solid is filtered after reaction is ended, is extracted by ethyl acetate, is dried, evaporated and dissolved to obtain a crude product which is subjected to columnchromatography isolation to obtain a rhodanine substitute; by taking piperidine as a catalyst, rhodanine substitute and aromatic formaldehyde react at the room temperature or under the reflux condition by taking dichloromethane or absolute ethyl alcohol as a solvent; and the reaction system is filtered while hot after reaction is ended to obtain the derivative of 2-thiothiazolidine-4-one. The synthesis route and equipment is simple, operations are simple, raw materials are cheap, the yield is high, the cost is reduced, economic benefits are improved, and is suitable for industrialized production.
Copper(II)-complex functionalized magnetite nanoparticles: a highly efficient heterogeneous nanocatalyst for the synthesis of 5-arylidenthiazolidine-2,4-diones and 5-arylidene-2-thioxothiazolidin-4-one
Akhavan, Malihe,Foroughifar, Naser,Pasdar, Hoda,Khajeh-Amiri, Alireza,Bekhradnia, Ahmadreza
, p. 543 - 552 (2017/08/15)
Abstract: Magnetite nanoparticles (MNPs) have proved to be a useful support for heterogeneous catalysis. We have synthesized Fe3O4 MNPs functionalized with a copper(II) complex, and tested the resulting material as a heterogeneous nanocatalyst. The catalyst was tested for aldol condensation reactions between aliphatic/aromatic aldehydes and rhodanine or thiazolidine-2,4-dione (TZD) derivatives under reflux in ethanol, giving the target products in high yield. Environmentally benign chemistry, short reaction times, simple work-up, excellent yields, and the reusability of the new nanocatalyst are beneficial features of the present study. The nanocatalyst was characterized by scanning electron microscopy, vibrating sample magnetometery, thermogravimetry, X-ray diffraction, and energy-dispersive X-ray analyses. The data showed that the magnetic nanoparticles are super-paramagnetic with a size range of 10–20?nm. Graphical Abstract: [Figure not available: see fulltext.].
Novel tetrazoloquinoline-rhodanine conjugates: Highly efficient synthesis and biological evaluation
Subhedar, Dnyaneshwar D.,Shaikh, Mubarak H.,Nawale, Laxman,Yeware, Amar,Sarkar, Dhiman,Khan, Firoz A. Kalam,Sangshetti, Jaiprakash N.,Shingate, Bapurao B.
supporting information, p. 2278 - 2283 (2016/04/20)
In search of new active molecules against Mycobacterium tuberculosis (MTB) H37Ra and Mycobacterium bovis BCG, a small focused library of rhodanine incorporated tetrazoloquinoline has been efficiently synthesized by using [HDBU][HSO4] acidic ionic liquid. The compound 3c found to be promising inhibitor of MTB H37Ra and M. bovis BCG characterized by lower MIC values 4.5 and 2.0 μg/mL, respectively. The active compounds were further tested for cytotoxicity against HeLa, THP-1, A549 and PANC-1 cell lines using MTT assay and showed no significant cytotoxic activity at the maximum concentration evaluated. Again, the synthesized compounds were found to have potential antifungal activity. Furthermore, to rationalize the observed biological activity data, the molecular docking study also been carried out against a potential target Zmp1 enzyme of MTB H37Ra, which revealed a significant correlation between the binding score and biological activity for these compounds. The results of in vitro and in silico study suggest that these compounds possess ideal structural requirement for the further development of novel therapeutic agents.
[Et3NH][HSO4] catalyzed efficient synthesis of 5-arylidene-rhodanine conjugates and their antitubercular activity
Subhedar, Dnyaneshwar D.,Shaikh, Mubarak H.,Nawale, Laxman,Yeware, Amar,Sarkar, Dhiman,Shingate, Bapurao B.
, p. 6607 - 6626 (2016/07/12)
Abstract: We have described a highly efficient, safer protocol for the synthesis of 5-arylidene-rhodanine conjugates catalyzed by Bronsted acidic ionic liquid [Et3NH][HSO4] in excellent yields. The protocol offers cost-effective, environmentally benign, solvent-free conditions and recycle–reuse of the catalyst. The synthesized 5-arylidene-rhodanine conjugates were characterized on the basis of 1H NMR, 13C NMR and HRMS spectral data. A series of 5-arylidene-rhodanine derivatives 3a–h, 4a–h were synthesized and evaluated for their in vitro antitubercular activity against dormant Mycobacterium tuberculosis H37Ra and M. bovis BCG strains. Moreover, compounds 3a, 3b, 3e, 3f, 3g, 3h and 4f exhibited good antitubercular activity and were also evaluated for anti-proliferative activity against MCF-7, A549 and HCT116 cell lines using modified MTT assay and found to be noncytotoxic. Compounds 3a–h and 4f were further screened for their antibacterial activity against four bacteria strains to assess their selectivity towards M. tuberculosis. Furthermore, in silico ADME prediction of all the tested compounds followed the criteria for orally active drug and, therefore, these compounds may have a good potential for eventual development as oral agents. Graphical Abstract: [Figure not available: see fulltext.]
Synthesis and biological evaluation of new rhodanine analogues bearing 2-chloroquinoline and benzo[h]quinoline scaffolds as anticancer agents
Ramesh, Vadla,Ananda Rao, Boddu,Sharma, Pankaj,Swarna,Thummuri, Dinesh,Srinivas, Kolupula,Naidu,Jayathirtha Rao, Vaidya
, p. 569 - 580 (2014/07/21)
Several rhodanine derivatives (9-39) were synthesized for evaluation of their potential as anticancer agents. Villsmeier cyclization to synthesize aza-aromatic aldehydes, rhodanine derivatives preparation and Knoevenagel type of condensation between the rhodanines and aza-aromatic aldehydes are key steps used for the synthesis of 31 compounds. In vitro antiproliferative activity of the synthesized rhodanine derivatives (9-39) was studied on a panel of six human tumor cell lines viz. HGC, MNK-74, MCF-7, MDAMB-231, DU-145 and PC-3 cell lines. Some of the compounds were capable of inhibiting the proliferation of cancer cell lines at a micromolar concentration. Six compounds are found to be potent against HGC cell lines; compound 15 is found to be active against HGC - Gastric, MCF7 - Breast Cancer and DU145 - Prostate Cancer cell lines; compound 39 is potent against MNK-74; four compounds are found to be potent against MCF-7 cell lines; three compounds are active against MDAMB-231; nine compounds are found to be potent against DU-145; three compounds are active against PC-3 cell lines. These compounds constitute a promising starting point for the development of novel and more potent anticancer agents in future.
