53101-19-2Relevant articles and documents
2-amino-4-arylthiazole derivatives as anti-giardial agents: Synthesis, biological evaluation and QSAR studies
Mocelo-Castell, Raul,Villanueva-Novelo, Carlos,Cáceres-Castillo, David,Carballo, Ruben M.,Quijano-Qui?ones, Ramiro F.,Quesadas-Rojas, Mariana,Cantillo-Ciau, Zulema,Cedillo-Rivera, Roberto,Moo-Puc, Rosa E.,Moujir, Laila M.,Mena-Rejón, Gonzalo J.
, p. 1127 - 1136 (2016/08/10)
A series of seven 2-amino-4-arylthiazoles were prepared following Hantzsch's modified method under microwave irradiation. A set of 50 derivatives was obtained and the in vitro activity against Giardia intestinalis was evaluated. The results on the biological activity revealed that, in general, the N-(5-bromo-4-aryl-thiazol-2-yl)-acetamide scaffold showed high bioactivity. In particular, compounds 6e (IC50= 0.39 μM) and 6b (IC50= 0.87 μM) were found to be more potent than the positive control metronidazole. Citoxicity and acute toxicity tests performed showed low toxicity and high selectivity of the most active compounds (6e SI = 139, 6b SI = 52.3). A QSAR analysis was applied to a data set of 37 obtained 2-amino-4-arylthiazoles derivatives and the best model described a strongly correlation between the anti-giardiasic activity and molecular descriptors as E2M, RDF115m, F10, MATS6v, and Hypnotic-80, with high statistical quality. This finding indicates that N-substituted aminothiazole scaffold should be investigated for the development of highly selective anti-giardial agent.
Sequence-specific base pair mimics are efficient topoisomerase IB inhibitors
Vekhoff, Pierre,Duca, Maria,Guianvarc'h, Dominique,Benhida, Rachid,Arimondo, Paola B.
experimental part, p. 43 - 51 (2012/05/20)
Topoisomerase IB controls DNA topology by cleaving DNA transiently. This property is used by inhibitors, such as camptothecin, that stabilize, by inhibiting the religation step, the cleavage complex, in which the enzyme is covalently attached to the 3'-phosphate of the cleaved DNA strand. These drugs are used in clinics as antitumor agents. Because three-dimensional structural studies have shown that camptothecin derivatives act as base pair mimics and intercalate between two base pairs in the ternary DNA- topoisomerase-inhibitor complex, we hypothesized that base pairs mimics could act like campthotecin and inhibit the religation reaction after the formation of the topoisomerase I-DNA cleavage complex. We show here that three base pair mimics, nucleobases analogues of the aminophenyl-thiazole family, once targeted specifically to a DNA sequence were potent topoisomerase IB inhibitors. The targeting was achieved through covalent linkage to a sequencespecific DNA ligand, a triplex-forming oligonucleotide, and was necessary to position and keep the nucleobase analogue in the cleavage complex. In the absence of triplex formation, only a weak binding to the DNA and topoisomerase I-mediated DNA cleavage was observed. The three compounds were equally active once conjugated, implying that the intercalation of the nucleobase upon triplex formation is the essential feature for the inhibition activity.
Vilsmeier Haack reaction of substituted 2-acetamidothiazole derivatives and their antimicrobial activity
Koti,Kolavi,Hegde,Khazi
, p. 1900 - 1904 (2007/10/03)
Vilsmeier Haack (VMH) reaction of 2-acetamidothiazole having carbethoxy group at C-4 affords the unexpected N-formylated product, which is followed by deacetylation. The same reaction with substituents other than carbethoxy group at C-4 position (viz CHs
