7520-95-8Relevant academic research and scientific papers
Novel cyanothiouracil and cyanothiocytosine derivatives as concentration-dependent selective inhibitors of U87MG glioblastomas: Adenosine receptor binding and potent PDE4 inhibition
Sahin, Zafer,Biltekin, Sevde Nur,Yurttas, Leyla,Berk, Barkin,?zhan, Ya?mur,Sipahi, Hande,Gao, Zhan-Guo,Jacobson, Kenneth A.,Demirayak, ?eref
, (2021/01/12)
Thiouracil and thiocytosine are important heterocyclic pharmacophores having pharmacological diversity. Antitumor and antiviral activity is commonly associated with thiouracil and thiocytosine derivatives, which are well known fragments for adenosine receptor affinity with many associated pharmacological properties. In this respect, 33 novel compounds have been synthesized in two groups: 24 thiouracil derivatives (4a-x) and 9 thiocytosine derivatives (5a-i). Antitumor activity of all the compounds was determined in the U87 MG glioblastoma cell line. Compound 5e showed an anti-proliferative IC50 of 1.56 μM, which is slightly higher activity than cisplatin (1.67 μM). The 11 most active compounds showed no signficant binding to adenosine A1, A2A or A2B receptors at 1 μM. Brain tumors express high amounts of phosphodiesterases. Compounds were tested for PDE4 inhibition, and 5e and 5f showed the best potency (5e: 3.42 μM; 5f: 0.97 μM). Remakably, those compounds were also the most active against U87MG. However, the compounds lacked a cytotoxic effect on the HEK293 healthy cell line, which encourages further investigation.
Synthesis and antimicrobial evaluation of new thiazolyl-1,2,3-triazolyl-alcohol derivatives
Bobade, Vivek D.,Chavan, Abhijit,Jagadale, Shivaji,Mhaske, Pravin C.,Shinde, Abhijit,Sisode, Vilas
, (2020/05/05)
A new series of 1-(4-methyl-2-aryl-1,3-thiazol-5-yl)-2-(4-aryl-1,2,3-triazol-1-yl)ethanol (6a-t) have been synthesized by a click reaction of 2-azido-1-(4-methyl-2-phenylthiazol-5-yl)ethanone (3a-e) with substituted ethynylbenzene (4a-c) followed by reduc
Dependence on the Pyrimidine Biosynthetic Enzyme DHODH Is a Synthetic Lethal Vulnerability in Mutant KRAS-Driven Cancers
Koundinya, Malvika,Sudhalter, Judith,Courjaud, Albane,Lionne, Bruno,Touyer, Gaetan,Bonnet, Luc,Menguy, Isabelle,Schreiber, Isabelle,Perrault, Christelle,Vougier, Stephanie,Benhamou, Brigitte,Zhang, Bailin,He, Timothy,Gao, Qiang,Gee, Patricia,Simard, Daniel,Castaldi, M. Paola,Tomlinson, Ronald,Reiling, Stephan,Barrague, Matthieu,Newcombe, Richard,Cao, Hui,Wang, Yanjun,Sun, Fangxian,Murtie, Joshua,Munson, Mark,Yang, Eric,Harper, David,Bouaboula, Monsif,Pollard, Jack,Grepin, Claudine,Garcia-Echeverria, Carlos,Cheng, Hong,Adrian, Francisco,Winter, Christopher,Licht, Stuart,Cornella-Taracido, Ivan,Arrebola, Rosalia,Morris, Aaron
, p. 705 - 11,717 (2018/06/21)
Activating KRAS mutations are major oncogenic drivers in multiple tumor types. Synthetic lethal screens have previously been used to identify targets critical for the survival of KRAS mutant cells, but their application to drug discovery has proven challenging, possibly due in part to a failure of monolayer cultures to model tumor biology. Here, we report the results of a high-throughput synthetic lethal screen for small molecules that selectively inhibit the growth of KRAS mutant cell lines in soft agar. Chemoproteomic profiling identifies the target of the most KRAS-selective chemical series as dihydroorotate dehydrogenase (DHODH). DHODH inhibition is shown to perturb multiple metabolic pathways. In vivo preclinical studies demonstrate strong antitumor activity upon DHODH inhibition in a pancreatic tumor xenograft model. Koundinya et al. show that inhibitors of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase selectively inhibit the growth of KRAS mutant cell lines. Differential sensitivity of the mutant lines correlates with differential effects of the inhibitors on primary energy metabolism and glutamine levels, and the inhibitors synergize with some clinically used anticancer agents.
Synthesis, Characterization, and Antimicrobial Screening of 4″-methyl-2,2″-diaryl-4,2′:4′,5″-terthiazole Derivatives
Nalawade, Jitendra,Mhaske, Pravin C.,Shinde, Abhijit,Patil, Sachin V.,Choudhari, Prafulla B.,Bobade, Vivek D.
, p. 1366 - 1374 (2018/04/25)
A series of novel 4″-methyl-2,2″-diaryl-4,2′:4′,5″-terthiazole (8a-p) derivatives has been synthesized and screened for antibacterial activity against four pathogenic bacteria, Escherichia coli, Pseudomonas flurescence, Staphylococcus aureus, and Bacillus subtilis. Among them, compounds 8a and 8j exhibited excellent antibacterial activity with minimum inhibitory concentration range of 1.0 to 5.3?μg/mL and compounds 8m and 8p exhibited moderate to good antibacterial activity with minimum inhibitory concentration range of 16.9 to 29.7?μg/mL against all tested strains. All the synthesized compounds were screened for their in vitro antifungal activity against Cocinida candida. Most of the compounds reported moderate antifungal activity. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimicrobial agent.
Fused Heterocycles: Synthesis and Antitubercular Activity of Novel 6-Substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine
Abhale, Yogita K.,Deshmukh, Keshav K.,Sasane, Amit V.,Chavan, Abhijit P.,Mhaske, Pravin C.
, p. 229 - 233 (2015/03/18)
(Chemical Equation Presented) A series of 6-substituted-2-(4-methyl-2-substituted phenylthiazol-5-yl)H-imidazo[1,2-a]pyridine derivatives 4a-4l is described. The antitubercular activity of the synthesized compounds was determined against Mycobacterium smegmatis MC2 155 strain. From the activity result, it was found that the phenyl or 4-fluorophenyl group at 2 position of thiazole nucleus and bromo substituent at 6 position of imidazo[1,2-a]pyridine showed good antitubercular activity.
Synthesis and Antimicrobial Evaluation of Some New 4,5′-Bisthiazoles
Rozsa, Tibor,Duma, Mihaela,Vlase, Laurian,Ionu?, Ioana,P?rn?u, Adrian,Tiperciuc, Br?ndu?a,Oniga, Ovidiu
, p. 999 - 1006 (2015/08/06)
Thiazole and bisthiazole derivatives represent a prevalent scaffold in the antimicrobial drug discovery. Therefore, we have decided to synthesize some new series of 4,5′-bisthiazoles. A total of 17 compounds were synthesized, their structural elucidation
Synthesis and biological screening of 2′-aryl/benzyl-2-aryl-4-methyl-4′,5-bithiazolyls as possible anti-tubercular and antimicrobial agents
Abhale, Yogita K.,Sasane, Amit V.,Chavan, Abhijit P.,Deshmukh, Keshav K.,Kotapalli, Sudha Sravanti,Ummanni, Ramesh,Sayyad, Sadikali F.,Mhaske, Pravin C.
, p. 340 - 347 (2015/03/18)
A series of 2′-aryl/benzyl-2-aryl-4-methyl-4′,5-bithiazolyl derivatives, 25-64 were synthesized and evaluated for inhibitory activity against Mycobacterium smegmatis MC2 155 strain and antimicrobial activities against four pathogenic bacteria Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Proteus vulgaris. Among them, compounds 40, 49, 50, and 54 exhibited moderate to good inhibition on the growth of the bacteria Mycobacterium smegmatis at the concentration of 30 μM. Compounds 26, 40, 44, 54 and 56 exhibited moderate to good antibacterial activity. Compound 5-(2′-(4-fluorobenzyl)thiazol-4′-yl)-2-(4-fluorophenyl)-4-methyl-thiazole (54) exhibited both antitubercular as well as antimicrobial activity against all tested strains.
General Photoinduced Sequential Electrocyclization/[1,9]-Sigmatropic Rearrangement/Ring-Opening Reaction of Diarylethenes
Lvov, Andrey G.,Shirinian, Valerii Z.,Zakharov, Alexey V.,Krayushkin, Mikhail M.,Kachala, Vadim V.,Zavarzin, Igor V.
, p. 11491 - 11500 (2015/12/04)
A novel and efficient photochemical transformation of diarylethenes comprising a five-membered heterocyclic ring and phenyl moiety is described. This reaction provides a simple method for the preparation of functionalized naphthalene derivatives via photorearrangement reaction of diarylethenes, and the process is characterized by high efficiency that was determined by NMR monitoring. Some mechanistic aspects of this process have been also explored. It was found that the reaction includes tandem transformation of three basic processes: the photocyclization of the hexatriene system, [1,9]-sigmatropic rearrangement, and heterocyclic ring opening. Diarylethenes with different heterocycle moieties (thiophene, benzo[b]thiophene, furan, indole, imidazole, thiazole, oxazole, pyrazole) have been involved into this process, and the target naphthalenes with good yields have been obtained. The opportunity for use in the transformation of diarylethenes with different heterocyclic residues permits synthesis of naphthalenes with desired functional groups. The general character and high efficiency of the reaction promise that the transformation can be an effective synthetic route for the annulation of benzene rings to various aromatic systems, including heterocycles.
Synthesis and anticancer activities of some thiazole derivatives
Kayagil, Ismail,Demirayak, Seref
scheme or table, p. 2197 - 2207 (2010/04/24)
In this study, 2-substituted 4-[3/4-(4-arylthiazole-2-yl)aminophenyl] thiazole derivatives and 2-[4-[2-substituted 4-methylthiazole-5-yl]thiazole-2- yl]amino-5-arylidenethiazoline-4-one derivatives have been synthesized. The cytotoxic and/or growth inhibitory effects of the 16 selected compounds were evaluated in vitro against approximately 66 human tumor cell lines derived from nine neoplastic diseases. Some of the compounds were found to act as anticancer agents.
Synthesis and antimicrobial activities of new 1,4-benzothiazines possessing thiazolyl/imidazolyl moieties
Bhingolikar,Ingle,Dengle,Bondge,Mane
, p. 703 - 704 (2007/10/03)
3-[4′-Methyl-2′-(4″-substituted-phenyl) thiazol-5′-yl]-1,4-benzothiazine hydrobromides (3A) and 3-[1′-(4″-substituted-phenyl)-2′-mercapto-4′ -imidazol-5′-yl]-1,4-benzothiazine hydrobromides (3B) were synthesized. 5-Acyl-4-methylthiazoles (1A) and 5-acyl-2-mercapto-4-methylimidazoles (1B) were brominated using phenyltrimethylammonium tribromide as selective brominating agent to obtain the corresponding bromoacyl products 2A and 2B. These bromoacyl products when cyclocondensed by refluxing with 2-aminobenzenethiol in alcohol yielded the title compounds 3A and 3B. They were screened against microorganisms.
