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.
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.
