10531-41-6Relevant academic research and scientific papers
Synthesis and properties of thiophene and dithiin functionalized tetrathiafulvalenes
Ertas, Erdal,Bildirir, Hakan,Sahin, Onur,Oksen, Ipek
, p. 1835 - 1844 (2013)
Syntheses of two analogues of tetrathiafulvalene (TTF), fused to 1,4-dithiin and thiophene rings, substituted with thiophene moieties, have been illustrated. The syntheses were accomplished through the reaction of a 1,8-diketone with phosphorus pentasulfide or Lawesson's reagent in boiling dry toluene. Conversion of the thioketones to their the oxo forms with mercury (II) acetate, was followed by self-coupling in freshly distilled boiling triethyl phosphite. Attempts for their electro-polymerizations through the thiophene groups at the peripherals were unsuccessful. Computational chemistry studies revealed that the thiophene groups did not exhibit enough spin densities to perform polymerization. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.
Synthesis and evaluation of 5,6-disubstituted thiopyrimidine aryl aminothiazoles as inhibitors of the calcium-activated chloride channel TMEM16A/Ano1
Piechowicz, Katarzyna A.,Truong, Eric C.,Javed, Kashif M.,Chaney, Rachelle R.,Wu, Johnny Y.,Phuan, Puay W.,Verkman, Alan S.,Anderson, Marc O.
, p. 1362 - 1368 (2016)
Transmembrane protein 16A (TMEM16A), also called Ano1, is a Ca2+ activated Cl? channel expressed widely in mammalian epithelia, as well as in vascular smooth muscle and some tumors and electrically excitable cells. TMEM16A inhibitors have potential utility for treatment of disorders of epithelial fluid and mucus secretion, hypertension, some cancers and other diseases. 4-Aryl-2-amino thiazole T16Ainh-01 was previously identified by high-throughput screening. Here, a library of 47 compounds were prepared that explored the 5,6-disubstituted pyrimidine scaffold found in T16Ainh-01. TMEM16A inhibition activity was measured using fluorescence plate reader and short-circuit current assays. We found that very little structural variation of T16Ainh-01 was tolerated, with most compounds showing no activity at 10 μM. The most potent compound in the series, 9bo, which substitutes 4-methoxyphenyl in T16Ainh-01 with 2-thiophene, had IC50 ～1 μM for inhibition of TMEM16A chloride conductance.
Synthesis of 2,4-diamino-5-(fur-2-oyl), (thien-2-oyl), and (pyrid-2-oyl)thiazoles
Chithralekha Devi,Rajasekharan
, p. 1523 - 1528 (2002)
The synthesis of 5-furoyl-, thienoyl- or pyridoyl-2,4-diamino- thiazoles, as the thiazole analogs of the cytotoxic marine alkaloid dendrodoine, is reported. A preliminary study on a tandem bromination-heterocyclization approach, amenable for a combinatori
Design, synthesis, antibacterial activity evaluation and molecular modeling studies of new sulfonamides containing a sulfathiazole moiety
Me?eli, Tu?ba,Do?an, ?engül Dilem,Gündüz, Miyase G?zde,K?kbudak, Zülbiye,Skaro Bogojevic, Sanja,Noonan, Theresa,Vojnovic, Sandra,Wolber, Gerhard,Nikodinovic-Runic, Jasmina
, p. 8166 - 8177 (2021)
Sulfonamides represent the oldest synthetic antibacterial agents; however, their central position in controlling bacterial diseases has been seriously damaged by the development of widespread resistance. Herein, we revisited sulfathiazole, a commercial member of antibacterial sulfa drugs, intending to overcome sulfonamide resistance and identify new drug candidates through molecular modifications. We synthesized twelve sulfonamides (SA1-SA12) by replacing the amino group on the phenyl ring with various substituents and introducing a thiophene ring on the core scaffold of sulfathiazole. The obtained compounds and additionally two commercial sulfonamides, sulfathiazole and sulfadiazine, were extensively screened for their antimicrobial activities. The results indicated that new sulfonamides, unlike traditional ones, were selectively effective against various Staphylococcus aureus strains. Introducing a bulky lipophilic substituent at the para position of the phenyl ring significantly increased the antibacterial activities of the compounds against Staphylococcus aureus. The compounds demonstrating favourable selectivity indices were further evaluated for their membrane potential perturbation and DNA interaction properties. The obtained data showed that these are not supporting mechanisms for the antibacterial activities of the modified sulfathiazole derivatives. In order to rationalize the activity of the three most active compounds, SA7, SA11 and SA12, against S. aureus ATCC 25923, their binding hypotheses within the catalytic site of Staphylococcus aureus dihydropteroate synthase, the validated target enzyme of sulfonamides, were generated via molecular docking and further dissected using molecular dynamics simulations and dynamic 3D pharmacophores (dynophores).
A focused structure-activity relationship study of psoralen-based immunoproteasome inhibitors
?terman, Andrej,Gobec, Martina,Gobec, Stanislav,Mravljak, Janez,Ra??an, Irena Mlinari?,Schiffrer, Eva Shannon,Sosi?, Izidor
, p. 1958 - 1965 (2019)
The immunoproteasome is a multicatalytic protease that is predominantly expressed in cells of hematopoietic origin. Its elevated expression has been associated with autoimmune diseases, various types of cancer, and inflammatory diseases. The development of immunoproteasome-selective inhibitors with non-peptidic scaffolds remains a challenging task. Here, we describe a focused series of psoralen-based inhibitors of the β5i subunit of the immunoproteasome with different substituents placed at position 4′. The most promising compound was further evaluated through changes at position 3 of the psoralen ring. Despite a small decrease in the inhibitory potency in comparison with the parent compound, we were able to improve the selectivity against other subunits of both the immunoproteasome and the constitutive proteasome. The most potent compounds discriminated between both proteasome types in cell lysates and also showed a decrease in cytokine secretion in peripheral blood mononuclear cells.
An easy synthesis of 2-haloacetylfurans and -thiophenes
Dubac,Gaset,Maraval
, p. 11 - 16 (1991)
The 2-chloro (or bromo)acetylfurans and -thiophenes were selectively synthesized with preservation of the heteroaromatic cycle from enoxysilane forms of 2-acetylfurane and -thiophene.
Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives
Sahin, Zafer,Ertas, Merve,Berk, Bark?n,Biltekin, Sevde Nur,Yurttas, Leyla,Demirayak, Seref
, p. 1986 - 1995 (2018)
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.
NBS mediated protocol for the synthesis of N-bridged fused heterocycles in water
Bhagat, Saket B.,Telvekar, Vikas N.
, p. 3662 - 3666 (2017)
A facile and environmental friendly protocol for the synthesis of N-bridged fused bicyclic compounds such as imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[2,1-b]thiazole, from commercially available starting materials has been developed.
Design, synthesis and in vitro cytotoxicity studies of novel β-carbolinium bromides
Venkataramana Reddy,Mishra, Shriprada,Tantak, Mukund P.,Nikhil, Kumar,Sadana, Rachna,Shah, Kavita,Kumar, Dalip
, p. 1379 - 1384 (2017)
A series of novel β-carbolinium bromides has been synthesized from easily accessible β-carbolines and 1-aryl-2-bromoethanones. The newly synthesized compounds were evaluated for their in vitro anticancer activity. Among the synthesized derivatives, compounds 16l, 16o and 16s exhibited potent anticancer activity with IC50values of 50= 3.16–7.93 μM). In order to test the mechanism of cell death, we exposed castration resistant prostate cancer cell line (C4-2) to compounds 16l and 16s, which resulted in increased levels of cleaved PARP1 and AO/EB staining, indicating that β-carbolinium salts induce apoptosis in these cells. Additionally, the most potent β-carbolines 16l and 16s were found to inhibit tubulin polymerization.
Design and synthesis of novel carbazolo-thiazoles as potential anti-mycobacterial agents using a molecular hybridization approach
Shaikh, Mahamadhanif S.,Palkar, Mahesh B.,Patel, Harun M.,Rane, Rajesh A.,Alwan, Wesam S.,Shaikh, Mahidansha M.,Shaikh, Iqbal M.,Hampannavar, Girish A.,Karpoormath, Rajshekhar
, p. 62308 - 62320 (2014)
Various substituted carbazolo-thiazoles (compounds 6a-6o) were synthesized in good yields using a molecular hybridization approach. The synthesized compounds were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at the National Institute of Allergy and Infectious Diseases (Bethesda, MD, USA). Among the tested series, compound 6c (minimum inhibitory concentration 21 μM) showed the most promising anti-mycobacterial activity. Brief structure-activity relationship studies showed that the electron-donating groups (OCH3 and OH), particularly on the phenyl ring of the thiazole motif, had a positive correlation with the anti-mycobacterial activity. In addition, they displayed low cytotoxicity against a mammalian Vero cell line using the MTT assay, thereby having a high therapeutic index. This study shows the importance of molecular hybridization and the scope for the development of carbazole-thiazole compounds as potential anti-mycobacterial agents.
