19241-17-9Relevant academic research and scientific papers
A catalyst-free method for the synthesis of 1,4,2-dithiazoles from isothiocyanates and hydroxylamine triflic acid salts
An, Zhenyu,Liu, Yafeng,Ren, Yi,Wang, Ting,Yan, Rulong
supporting information, p. 6206 - 6209 (2021/07/28)
A catalyst-free method for the preparation of 1,4,2-dithiazoles is developed by reactions of isothiocyanates with hydroxylamine triflic acid salts. This reaction achieves C-S, C-N, and S-N bond formation, and a range of products are obtained in moderate to good yields. The obvious feature is using shelf-stable hydroxylamine triflic acid salts as a N source to synthesize heterocycles under mild conditions.
Design, computational studies, synthesis and biological evaluation of thiazole-based molecules as anticancer agents
Anuradha,Patel, Sagarkumar,Patle, Rajkumar,Parameswaran, Preethi,Jain, Alok,Shard, Amit
, p. 20 - 30 (2019/04/25)
Background: Abolition of cancer warrants effective treatment modalities directed towards specific pathways dysregulated in tumor proliferation and survival. The antiapoptotic Bcl-2 proteins are significantly altered in several tumor types which position them as striking targets for therapeutic intervention. Here we designed, computationally evaluated, synthesized, and biologically tested structurally optimized thiazole-based small molecules as anticancer agents. Methods: The virtually designed 200 molecules were subjected to rigorous docking and in silico ADME-Toxicity studies. Out of this, 23 skeletally diverse thiazole-based molecules which passed pan assay interference compounds (PAINS) filter and were synthetically feasible were synthesized in 3 steps using cheap and readily available reagents. The molecules were in vitro evaluated against Bcl-2-Jurkat, A-431 cancerous cell lines and ARPE-19 cell lines. Molecular Dynamics (MD) simulation studies were performed to analyse conformational changes induced by ligand 32 in Bcl-2. Flow cytometry analysis of compound 32 treated Bcl-2 cells was done to check apoptosis. Results: The molecules exhibited appreciable interactions with Bcl-2 and were having acceptable drug like properties as tested in silico. The multi step synthesis yielded 23 skeletally diverse thiazole-based molecules in up to 80% yield. The molecules simultaneously inhibited Bcl-2 Jurkat cells in vitro without causing detectable toxicity to normal cells (ARPE-19 cells). Among them molecules 32, 50, 53, 57 and 59 showed considerable activities against Bcl-2 Jurkat and A-431cell lines at concentrations ranging from 32–46 μM and 34–52 μM, respectively. The standard doxorubicin exhibited IC50 in Bcl-2 Jurkat and A-431cell lines at 45.87 μM and 42.37 μM, respectively. The molecule 32, almost equipotent in both the cell lines was subjected to molecular dynamics (MD) simulation with Bcl-2 protein (4IEH). It was shown that 32 interacted with protein majorly via hydrophobic interactions and few H-bonding interactions. Fluorescence-activated cell sorting (FACS) analysis established that molecule is dragging cancerous cells towards apoptosis. Discussion and conclusion: The chemical intuition was checked by computation coupled with biological results confirmed that thiazole-based hits have the potential to be developed downstream into potent and safer leads against antiapoptotic Bcl-2 cells.
A block containing nicotinamide diphenyl thiourea compound and its salt preparation method and use of
-
Paragraph 0085; 0086; 0097, (2017/08/02)
The invention relates to a diphenyl thiourea compound containing niacinamide building blocks and salt of the diphenyl thiourea compound. The chemical structure of the diphenyl thiourea compound is as shown in the description. The diphenyl thiourea compound and the salt, pharmaceutically acceptable, of the diphenyl thiourea compound have inhibiting effects on various tumour cell strains and can serve as effective components for preparing tumour treatment medicine.
Synthesis and bioevaluation of N,4-diaryl-1,3-thiazole-2-amines as tubulin inhibitors with potent antiproliferative activity
Sun, Maolin,Xu, Qile,Xu, Jingwen,Wu, Yue,Wang, Yueting,Zuo, Daiying,Guan, Qi,Bao, Kai,Wang, Jian,Wu, Yingliang,Zhang, Weige
, (2017/04/01)
A series of N,4-diaryl-1,3-thiazole-2-amines containing three aromatic rings with an amino linker were designed and synthesized as tubulin inhibitors and evaluated for their antiproliferative activity in three human cancer cell lines. Most of the target compounds displayed moderate antiproliferative activity, and N-(2,4-dimethoxyphenyl)-4-(4-methoxyphenyl)-1,3-thiazol-2-amine (10s) was determined to be the most potent compound. Tubulin polymerization and immunostaining experiments revealed that 10s potently inhibited tubulin polymerization and disrupted tubulin microtubule dynamics in a manner similar to CA-4. Moreover, 10s effectively induced SGC-7901 cell cycle arrest at the G2/M phase in both concentrationand time-dependent manners. The molecular docking results revealed that 10s could bind to the colchicine binding site of tubulin.
Synthesis and biological evaluation of terminal functionalized thiourea-containing dipeptides as antitumor agents
Huang, Ri-Zhen,Zhang, Bin,Huang, Xiao-Chao,Liang, Gui-Bin,Qin, Jian-Mei,Pan, Ying-Ming,Liao, Zhi-Xin,Wang, Heng-Shan
, p. 8866 - 8878 (2017/02/10)
A series of antitumor agents based on terminal functionalized dipeptide derivatives containing the thiourea moiety were synthesized and evaluated for antiproliferative activity using a panel of cancer cell lines, and the effects and mechanism of apoptosis induction were determined. These compounds exhibited significant selectivity to different cancer cell lines with IC50 values at micromolar concentrations. In particular, compound I-11 appeared to be the most potent compound, with an IC50 = 4.85 ± 1.44 μM against the NCI-H460 cell line, at least partly, by the induction of apoptosis. Mechanistically, compound I-11 induced the activation of caspase-12 and CHOP, which triggered apoptotic signalling via the ROS-dependent endoplasmic reticulum pathway and arrested the cell cycle at the S phase. Thus, we concluded that dipeptide derivatives containing the thiourea moiety terminally functionalized by electron-withdrawing substituents may be potential antitumor agents for further investigation.
Design, synthesis and biological evaluation of thiourea and nicotinamide-containing sorafenib analogs as antitumor agents
Kong, Xiangkai,Yao, Zeyu,He, Zuopeng,Xu, Wenfang,Yao, Jianwen
supporting information, p. 867 - 870 (2015/05/27)
A series of thiourea and nicotinamide-containing sorafenib analogs (7a-n) were designed and synthesized and their antiproliferative activities were tested against HCT116, MDA-MB-231, PC-3 and HepG2 cell lines. Most of the compounds showed potent activities against the four cell lines, compound 7h showed better activities than sorafenib against all four cell lines, and compounds 7a and 7e showed better activities against HCT116 and MDA-MB-231 cell lines. The anti-angiogenic activities of 7e and 7h were also better than that of sorafenib in both in vitro HUVEC tube formation assay and ex vivo rat thoracic aorta ring assay.
Design, synthesis and in vitro evaluation of novel ursolic acid derivatives as potential anticancer agents
Hua, Shi-Xian,Huang, Ri-Zhen,Ye, Man-Yi,Pan, Ying-Ming,Yao, Gui-Yang,Zhang, Ye,Wang, Heng-Shan
, p. 435 - 452 (2015/04/14)
A series of novel ursolic acid (UA) derivatives modified at the C-3 and the C-28 positions were designed and synthesized in an attempt to develop potential antitumor agents. The in vitro cytotoxicity were evaluated against five cancer cell lines (MGC-803, HCT-116, T24, HepG2 and A549 cell lines) and a normal cell (HL-7702) by MTT assay. The screening results indicated that some of these target compounds displayed moderate to high levels of antiproliferative activities compared with ursolic acid and 5-fluorouracil (5-FU), and exhibited much lower cytotoxicity than 5-FU, indicating that the targeted compounds had selective and significant effect on the cell lines. The induction of apoptosis and affects on the cell cycle distribution of compound 6r were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining and flow cytometry, which revealed that the antitumor activity of 6r was possibly achieved through the induction of cell apoptosis by G1 cell-cycle arrest. Western blot and qRT-PCR (quantitative real-time PCR) experiments demonstrated that compound 6r may induce apoptosis through both of intrinsic and extrinsic apoptosis pathway.
Design, synthesis, X-ray crystallographic analysis, and biological evaluation of thiazole derivatives as potent and selective inhibitors of human dihydroorotate dehydrogenase
Zhu, Junsheng,Han, Le,Diao, Yanyan,Ren, Xiaoli,Xu, Minghao,Xu, Liuxin,Li, Shiliang,Li, Qiang,Dong, Dong,Huang, Jin,Liu, Xiaofeng,Zhao, Zhenjiang,Wang, Rui,Zhu, Lili,Xu, Yufang,Qian, Xuhong,Li, Honglin
, p. 1123 - 1139 (2015/03/04)
Human dihydroorotate dehydrogenase (HsDHODH) is a flavin-dependent mitochondrial enzyme that has been certified as a potential therapeutic target for the treatment of rheumatoid arthritis and other autoimmune diseases. On the basis of lead compound 4, which was previously identified as potential HsDHODH inhibitor, a novel series of thiazole derivatives were designed and synthesized. The X-ray complex structures of the promising analogues 12 and 33 confirmed that these inhibitors bind at the putative ubiquinone binding tunnel and guided us to explore more potent inhibitors, such as compounds 44, 46, and 47 which showed double digit nanomolar activities of 26, 18, and 29 nM, respectively. Moreover, 44 presented considerable anti-inflammation effect in vivo and significantly alleviated foot swelling in a dose-dependent manner, which disclosed that thiazole-scaffold analogues can be developed into the drug candidates for the treatment of rheumatoid arthritis by suppressing the bioactivity of HsDHODH.
Novel selective and potent inhibitors of malaria parasite dihydroorotate dehydrogenase: Discovery and optimization of dihydrothiophenone derivatives
Xu, Minghao,Zhu, Junsheng,Diao, Yanyan,Zhou, Hongchang,Ren, Xiaoli,Sun, Deheng,Huang, Jin,Han, Dongmei,Zhao, Zhenjiang,Zhu, Lili,Xu, Yufang,Li, Honglin
, p. 7911 - 7924 (2013/11/06)
Taking the emergence of drug resistance and lack of effective antimalarial vaccines into consideration, it is of significant importance to develop novel antimalarial agents for the treatment of malaria. Herein, we elucidated the discovery and structure-activity relationships of a series of dihydrothiophenone derivatives as novel specific inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH). The most promising compound, 50, selectively inhibited PfDHODH (IC50 = 6 nM, with >14 000-fold species-selectivity over hDHODH) and parasite growth in vitro (IC50 = 15 and 18 nM against 3D7 and Dd2 cells, respectively). Moreover, an oral bioavailability of 40% for compound 50 was determined from in vivo pharmacokinetic studies. These results further indicate that PfDHODH is an effective target for antimalarial chemotherapy, and the novel scaffolds reported in this work might lead to the discovery of new antimalarial agents.
Environmentally benign one-pot synthesis of cyanamides from dithiocarbamates using I2 and H2O2
Jamir, Latonglila,Sinha, Upasana Bora,Nath, Jayashree,Patel, Bhisma K.
experimental part, p. 951 - 958 (2012/02/01)
An environmentally benign reaction is devised for the synthesis of cyanamides from dithiocarbamate salts using iodine and H2O 2. Taylor & Francis Group, LLC.
