61291-92-7Relevant academic research and scientific papers
Design, synthesis and biological evaluation of novel thiazole-derivatives as mitochondrial targeting inhibitors of cancer cells
Dang, Xin,Lei, Shuwen,Luo, Shuhua,Hu, Yixin,Wang, Juntao,Zhang, Dongdong,Lu, Dan,Jiang, Faqin,Fu, Lei
, (2021/06/16)
Mitochondria are pivotal energy production sources for cells to maintain necessary metabolism activities. Targeting dysfunctional mitochondrial features has been a hotspot for mitochondrial-related disease researches. Investigation with cancerous mitochondrial metabolism is a continuing concern within tumor therapy. Herein, we set out to assess the anti-cancer activities of a novel family of TPP-thiazole derivatives based on our earlier research on mitochondrial targeting agents. Specifically, we designed and synthesized a series of TPP-thiazole derivatives and revealed by the MTT assay that most synthesized compounds effectively inhibited three cancer cell lines (HeLa, PC3 and MCF-7). After structure modifications, we explored the SAR relationships and identified the most promising compound R13 (IC50 of 5.52 μM) for further investigation. In the meantime, we performed ATP production assay to assess the selected compounds inhibitory effect on HeLa cells energy production. The results displayed the test compounds significantly restrained ATP production of cancer cells. Overall, we have designed and synthesized a series of compounds which exhibited significant cytotoxicity against cancer cells and effectively inhibited mitochondrial energy production.
Synthesis and antimycobacterial evaluation of new 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives
Shinde, Vikas,Mahulikar, Pramod,Mhaske, Pravin C.,Chakraborty, Shakti,Choudhari, Amit,Phalle, Siddharth,Choudhari, Prafulla,Sarkar, Dhiman
, p. 805 - 819 (2019/04/26)
A new series of 5-(1-benzyl-1H-1,2,3-triazol-4-yl)-4-methyl-2-arylthiazole derivatives, 6a?w have been synthesized by click reaction of substituted benzylazide, 5a?d with 5-ethynyl-4-methyl-2-substituted phenylthiazole, 4a?f. The starting compounds 4-ethy
Synthesis, antitubercular and antimicrobial potential of some new thiazole substituted thiosemicarbazide derivatives
Abhale, Yogita K.,Shinde, Abhijit,Deshmukh, Keshav K.,Nawale, Laxman,Sarkar, Dhiman,Mhaske, Pravin C.
, p. 2557 - 2567 (2017/10/06)
The increase in antibiotic resistance due to multiple factors has warranted the need for search of new compounds which are active against multidrug resistant pathogens. In this context a small focused library of thiosemicarbazide derivatives of 2-arylthiazole-4-carbaldehyde, 4-methyl-2-arylthiazole-5-carbaldehyde and 1-(4-methyl-2-arylthiazol-5-yl) ethanone, (5a–l) has been synthesized. The title compounds were screened for inhibitory activity against Mycobacterium tuberculosis H37Ra (ATCC 25177) and Mycobacterium bovis Bacille Calmette Guerin (ATCC 35743) strains. The synthesized compounds, 5a–l were further assayed for their cytotoxic activity against the two human cancer cell lines, HeLa and human colon carcinoma 116 cell lines and showed no significant cytotoxic activity against these two cell lines at the maximum concentration evaluated. Further, the synthesized compounds were found to have potential antibacterial activity against Gram-negative bacteria, Escherichia coli, Pseudomonas flurescence and Gram-positive bacteria, Staphylococcus aureus, Bacillus subtilis. Most of the synthesized compounds showed moderate activity against fungal strain Candida albicans. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimycobacterial agent.
Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
Li, Zheng,Qiu, Qianqian,Xu, Xue,Wang, Xuekun,Jiao, Lei,Su, Xin,Pan, Miaobo,Huang, Wenlong,Qian, Hai
, p. 246 - 257 (2016/03/08)
The free fatty acid receptor 1 (FFA1/GPR40) has attracted interest as a novel target for the treatment of type 2 diabetes. Several series of FFA1 agonists including TAK-875, the most advanced compound terminated in phase III studies due to concerns about liver toxicity, have been hampered by relatively high molecular weight and lipophilicity. Aiming to develop potent FFA1 agonists with low risk of liver toxicity by decreasing the lipophilicity, the middle phenyl of TAK-875 was replaced by 11 polar five-membered heteroaromatics. Subsequently, systematic exploration of SAR and application of molecular modeling, leads to the identification of compound 44, which was an excellent FFA1 agonist with robustly hypoglycemic effect both in normal and type 2 diabetic mice, low risks of hypoglycemia and liver toxicity even at the twice molar dose of TAK-875. Meanwhile, two important findings were noted. First, the methyl group in our thiazole series occupied a small hydrophobic subpocket which had no interactions with TAK-875. Furthermore, the agonistic activity revealed a good correlation with the dihedral angle between thiazole core and the terminal benzene ring. These results promote the understanding of ligand-binding pocket and might help to design more promising FFA1 agonists.
Heterocyclic derivatives in the treatment of Ischaemia and related diseases
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, (2008/06/13)
Compounds of the formula: STR1 wherein A, R1, R2, R3 and m are defined as in the specification or a pharmaceutically acceptable acid addition salt or N-oxide thereof, are calcium and sodium channel antagonists useful for treating mammals having a variety of disease states, such as stroke, epilepsy, hypertension, angina, migraine, arrhythmia, thrombosis, embolism, and also for treatment of spinal injuries.
