61786-00-3Relevant 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.
I2/TBHP-Mediated tandem cyclization and oxidation reaction: Facile access to 2-substituted thiazoles and benzothiazoles
Liu, Li,Tan, Chen,Fan, Rong,Wang, Zihan,Du, Hongguang,Xu, Kun,Tan, Jiajing
supporting information, p. 252 - 256 (2019/01/10)
The efficient synthesis of 2-substituted thiazoles and benzothiazoles has been accomplished employing readily available cysteine esters and 2-aminobenzenethiols as N and S sources. The reaction proceeds under an I2/TBHP system and involves a on
A concise and efficient route to the total synthesis of bacillamide A and its analogues
Kumar, Sunil,Aggarwal, Ranjana
, p. 354 - 361 (2018/07/05)
The synthesis of bacillamide A, a tryptamide alkaloid of marine origin, and its analogues from L-cysteine ethyl ester hydrochloride through an efficient and convergent synthetic approach is described in this work. The present two-step protocol involves th
Synthesis and biological evaluation of new 2-aryl-4-((4-aryl-1H-1,2,3-triazol-1-yl)methyl)thiazole derivatives
Shinde, Vikas,Mahulikar, Pramod,Mhaske, Pravin C.,Nawale, Laxman,Sarkar, Dhiman
, p. 1247 - 1260 (2017/10/23)
A series of 2-aryl-4-((4-aryl-1H-1,2,3-triazol-1-yl)methyl)thiazole derivatives (8a–p) have been synthesized. The structure of the newly synthesized compounds was determined by spectral analysis. The title compounds were screened for their preliminary ant
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.
Solvent-free synthesis of bacillamide analogues as novel cytotoxic and anti-inflammatory agents
Kumar, Sunil,Aggarwal, Ranjana,Kumar, Virender,Sadana, Rachna,Patel, Bhumi,Kaushik, Pawan,Kaushik, Dhirender
, p. 718 - 726 (2016/08/15)
Synthesis of fourteen analogues of bacillamide, a bioactive tryptamide alkaloid of marine origin, has been accomplished through a highly efficient convergent route. The present solvent-free protocol involves the formation of thiazole ring in the initial step followed by amide coupling between substituted ethyl 2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxylates and tryptamine in presence of 2-hydroxy-4,6-dimethylpyrimidine, a solid phase catalyst to yield N-[2-(1H-indol-3-yl)ethyl]-2-alkyl/aryl/heteroaryl/amino/aminoarylthiazole-4-carboxamides as bacillamide analogues having structural variation at position-2 of thiazole ring. Bacillamide and its analogues were evaluated for their cytotoxic activity against three cancer cell lines (HCT-116, MDA-MD-231 and JURKAT cell lines) using colorimetric cell proliferation assay. Compounds 17a and 17b exhibited potent anti-cell proliferation activity with IC50values in the range of ～3.0?μM and ～0.1–0.6?μM, respectively against these cell lines. Preliminary mechanism of action studies indicates that these compounds initiate caspase dependent apoptosis. Also, compounds 16d, 16f, 17a and 17d exhibited excellent anti-inflammatory activity comparable to well-known NSAID indomethacin and better to bacillamide, when evaluated using carrageenan induced rat hind paw oedema method.
Synthesis, crystal structure, anti-HIV, and antiproliferative activity of new oxadiazole and thiazole analogs
Khan, Mahmood-ul-Hassan,Hameed, Shahid,Akhtar, Tashfeen,Al-Masoudi, Najim A.,Al-Masoudi, Wasfi A.,Jones, Peter G.,Pannecouque, Christophe
, p. 2399 - 2409 (2016/10/25)
A series of 2-adamantyl-5-arylthiazolyl-1,3,4-oxadiazoles 7a–x together with thiazoles 13 and 14 were synthesized. Compounds 7a–l, 13, and 14 were tested in vitro with the aim of identifying novel lead compounds active against human immunodeficiency virus type-1 and human immunodeficiency virus type-2 activity in MT-4 cells. Title compounds were also tested against representatives of Gram-positive and Gram-negative bacteria (Staphylococcus aureus, Salmonella spp.), various mycobacterial strains (Mycobacterium fortuitum and Mycobacterium smegmatis), yeast (Candida albicans), and mold (Aspergillus fumigatus). None of the compounds showed antiviral or antimicrobial activity, except compounds 13 and 14 exhibited anti-human immunodeficiency virus-1 activity with EC50 values of 1.79 and 2.39 μM with Selectivity index = 18 and 4, respectively. On the other hand, compounds 7a and 7j showed a marked cytotoxicity against the human CD4+ lymphocytes (MT-4). Therefore, 7a and 7j were evaluated for their antiproliferative activity against two solid tumor-derived cell lines, which exhibited IC50 values of 8.1 ± 0.10 μM and 4.8 ± 0.08 μM against Hep-G2 cell lines, respectively.
Powerful Antibacterial Activity of Phenyl-Thiolatobismuth(III) Complexes Derived from Oxadiazolethiones
Luqman, Ahmad,Blair, Victoria L.,Brammananth, Rajini,Crellin, Paul K.,Coppel, Ross L.,Andrews, Philip C.
, p. 4935 - 4945 (2015/11/02)
Seven novel 5-substituted phenylthiazole oxadiazolethiones: [Me-PTOT(H)], [MeO-PTOT(H)], [MeS-PTOT(H)], [F-PTOT(H)], [Cl-PTOT(H)], [Br-PTOT(H)], and [CF3-PTOT(H)], {where X-PTOT(H) = 5-[2-(4-X)thiazol-4-yl]-1,3,4-oxadiazole-2(3H)-thione, 4-X = C6H4}, were synthesised from their corresponding thioamides. From these seven heteroleptic thiolatobismuth complexes: BiPh(Me-PTOT)2 6, BiPh(MeO-PTOT)2 7, BiPh(MeS-PTOT)2 8, BiPh(F-PTOT)2 9, BiPh(Cl-PTOT)2 10, BiPh(Br-PTOT)2 11 and BiPh(CF3-PTOT)2 12 were synthesised and characterised. Complexes [10(DMSO)2] and [11(DMSO)2] were structurally characterised using X-ray diffraction. Evaluation of the antibacterial properties of the thiones and their BiIII complexes against Mycobacterium smegmatis, Staphylococcus aureus (S. aureus), Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), Enterococcus faecalis (E. faecalis) and Escherichia coli (E. coli) showed that all bismuth(III) complexes were highly effective against all the bacteria, as demonstrated by very low MIC values (1.1-2.1 μM). Complexes BiPh(Me-PTOT)2 6, BiPh(Cl-PTOT)2 10 and BiPh(Br-PTOT)2 11, showed best activity against the multi-drug resistant bacteria VRE and MRSA with an MIC value of 1.0 μM. All these complexes and their corresponding thiones failed to show any prominent activity against M. smegmatis and E. coli, even at high concentrations. These complexes showed little or no toxicity towards mammalian COS-7 cells at 20 μg/mL. Seven heteroleptic thiolatobismuth(III) complexes [BiPh(X-PTOT)2] derived from a series of 5-substituted phenylthiazole oxadiazolethiones [X-PTOT(H)] provide powerful antibacterial action against the multi-resistant bacteria MRSA and VRE.
Discovery of the disubstituted oxazole analogues as a novel class anti-tuberculotic agents against MDR- and XDR-MTB
Li, Dongsheng,Gao, Nana,Zhu, Ningyu,Lin, Yuan,Li, Yan,Chen, Minghua,You, Xuefu,Lu, Yu,Wan, Kanglin,Jiang, Jian-Dong,Jiang, Wei,Si, Shuyi
supporting information, p. 5178 - 5181 (2015/11/09)
A high-throughput screening effort on 45,000 compounds resulted in the discovery of a disubstituted oxazole as a new structural class inhibitor of Mycobacterium tuberculosis (Mtb). In order to improve the activity and investigate the SAR of this scaffold, a series of disubstituted azole analogues have been designed and synthesized. The newly synthesized compounds 1a-y were evaluated for their in vitro anti-TB activity versus replicating, multi- and extensive drug resistant Mtb strains. All the compounds, except 1o, 1p and 1q, showed potent anti-TB activity with MIC of 1-64 mg/L. The test of broad spectrum panel revealed that this series are specific to Mtb. The cytotoxicity assessment indicated that the compounds were not cytotoxic against HEK 293 cells. The compounds could have a novel mechanism to anti-Mtb as they can inhibit drug sensitive and drug resistant Mtb.
ENZYME INTERACTING AGENTS
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Paragraph 0146, (2016/05/19)
The present disclosure relates generally, but not exclusively, to compounds and their use as enzyme interacting agents, in particular, agents which interact with one or more enzymes in the sphingolipid biosynthesis pathway. The disclosure further relates
