31541-33-0Relevant academic research and scientific papers
Design, synthesis,: In silico molecular modelling studies and biological evaluation of novel indole-thiazolidinedione hybrid analogues as potential pancreatic lipase inhibitors
George, Ginson,Auti, Prashant S.,Paul, Atish T.
, p. 1381 - 1394 (2021/02/06)
Pancreatic lipase (PL) is a key enzyme responsible for the digestion of dietary triglycerides; hence its inhibition is considered as a promising target for the management and/or treatment of obesity. A new series of indole-thiazolidinedione (TZD) hybrid analogues were synthesized using a molecular hybridisation approach and evaluated for their anti-obesity effects via PL inhibition. The targeted analogues were synthesized via the condensation reaction between various substituted isatin with TZD in the presence of aqueous KOH in methanol. Amongst the synthesized analogues, 7k and 7m exhibited a potential PL inhibitory activity (IC50-7.30 and 9.51 μM, respectively). Kinetic study of these potent analogues revealed their competitive mode of enzyme inhibition. This fact was confirmed via fluorescence spectroscopy which further suggested the presence of one binding site for the synthesized analogues. Molecular docking of the synthesized analogues was performed using human PL (PDB ID: 1LPB). The obtained MolDock scores were aligned with the in vitro PL inhibitory activity (Pearson's r = 0.9108, p 0.05). Moreover, a stable conformation of the 1LPB-ligands suggested the stability of these complexes in the dynamic environment. These studies provided a basis for the potential role of the indole-TZD hybrids in PL inhibition and further optimization might result in the development of new lead candidates for obesity treatment.
Synthesis and evaluation of 3-ylideneoxindole acetamides as potent anticancer agents
Chiou, Chun-Tang,Lee, Wei-Chun,Liao, Jiahn-Haur,Cheng, Jing-Jy,Lin, Lie-Chwen,Chen, Chih-Yu,Song, Jen-Shin,Wu, Ming-Hsien,Shia, Kak-Shan,Li, Wen-Tai
, p. 1 - 12 (2015/05/27)
Indirubin, an active component in the traditional Chinese medicine formula Danggui Longhui Wan, shows promising anticancer effects. Meisoindigo is an analog derived from indirubin, which is less toxic and appears to be even more potent against cancer. In considering meisoindigo as a structural template for the development of new drugs, we designed and synthesized a series of 3-ylideneoxindole acetamides as novel anticancer agents. The acetamides were then evaluated for in vitro and in vivo anticancer activities. The 3-ylideneoxindole acetamides were found to have better anticancer activity than was indirubin-3'-oxime in several cancer cell lines and also displayed a spectrum of activity similar to that of the drug candidate roscovitine, a CDK inhibitor. Among the 3-ylideneoxindole acetamides, compound 10 showed particularly good efficacy. Cell cycle analysis further revealed that compound 10 arrested cells in the G1 phase and caused an increase in the sub-G1 population, indicating that the apoptosis pathway had been induced. In addition, exposure of cells to compound 10 led to the upregulation of the cell-cycle regulator cyclin D1, which was sustained at a high level. In contrast, the same compound induced a short-term elevation in the level of cyclin E, which was followed by a rapid decrease and the attenuation of Rb phosphorylation. Furthermore, a docking model suggests that compound 10 binds to the active site of CDK4. In testing the therapeutic potency of compound 10 on CT26-xenografted BALB/c mice, a significant reduction in tumor size comparable to that of cisplatin was found when administrated via the i.p. route. The mice presented no loss of body weight, indicating that this compound possesses low toxicity. In the future, we are planning in vivo investigations of these new active anticancer agents to better elucidate active mechanisms at the cellular level and thus benefit the development of anticancer therapies.
Enantioselective cyanoethoxycarbonylation of isatins promoted by a Lewis base-Bronsted acid cooperative catalyst
Ogura, Yoshihiro,Akakura, Matsujiro,Sakakura, Akira,Ishihara, Kazuaki
supporting information, p. 8299 - 8303 (2013/09/02)
Teaming up to make it happen: In the title reaction, the Lewis basic site of the catalyst activated ethyl cyanoformate, and the deep and flexible Bronsted acidic cavity stabilized and selectively recognized the key reaction intermediate to promote asymmet
Reaction of isatin with alkylating agents with acidic methylenes
Shmidt, María S.,Perillo, Isabel A.,González, Mercedes,Blanco, María M.
supporting information; experimental part, p. 2514 - 2517 (2012/06/18)
The reaction of isatin (1) with different alkyl halides 2 and alkaline carbonates in aprotic polar solvents leads mainly to N-alkyl derivatives 3. The use of alkylating agents that have acidic methylenes leads to competitive formation of the corresponding epoxide 5. The formation of 5 is favored by low-polarity solvents at low temperatures and strong bases. Epoxides 5c, d obtained using NaEtOH/EtOH at 0-5 °C are transformed into the corresponding 4-quinolinones 6 at higher temperatures. The use of Ag2CO3 allows obtaining compounds 3 as major products, along with varying amounts of labile O-alkyl derivatives 4 and dimerization products.
Identification and further development of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B
Vintonyak, Viktor V.,Warburg, Karin,Over, Bj?rn,Hübel, Katja,Rauh, Daniel,Waldmann, Herbert
experimental part, p. 6713 - 6729 (2011/10/01)
Tuberculosis continues to be a major cause of morbidity and mortality throughout the world. Protein tyrosine phosphatases from Mycobacterium tuberculosis are attractive targets for developing novel strategies in battling tuberculosis due to their role in
De novo design and synthesis of HIV-1 integrase inhibitors
Makhija, Mahindra T.,Kasliwal, Rajesh T.,Kulkarni, Vithal M.,Neamati, Nouri
, p. 2317 - 2333 (2007/10/03)
Existing AIDS therapies are out of reach for most HIV-infected people in developing countries and, where available, they are limited by their toxicity and their cost. New anti-HIV agents are needed urgently to combat emerging viral resistance and reduce the side effects associated with currently available drugs. Toward this end, LeapFrog, a de novo drug design program was used to design novel, potent, and selective inhibitors of HIV-1 integrase. The designed compounds were synthesized and tested for in vitro inhibition of HIV-1 integrase. Out of the 25 compounds that were designed, and synthesized, four molecules (compounds 23, 26, 43, and 59) showed moderate to low inhibition of HIV-1 integrase for 3′-processing and 3′- strand transfer activities. Nonetheless, these compounds possess structural features not seen in known HIV-1 integrase inhibitors and thus can serve as excellent leads for further optimization of anti-HIV-1 integrase activity.
