94794-27-1Relevant articles and documents
Halogenated aromatic thiosemicarbazones as potent inhibitors of tyrosinase and melanogenesis
Ha?dys, Katarzyna,Goldeman, Waldemar,Jewgiński, Micha?,Wolińska, Ewa,Anger-Góra, Natalia,Rossowska, Joanna,Latajka, Rafa?
, (2019/12/11)
A set of 21 halogenated thiosemicarbazones (TSCs) have been synthesized and its inhibitory properties toward activity diphenolase of mushroom tyrosinase and their ability to inhibition of melanogenesis in B16F10 murine, melanoma cell line have been invest
Novel tyrosyl-DNA phosphodiesterase 1 inhibitors enhance the therapeutic impact of topoteсan on in vivo tumor models
Zakharenko,Luzina,Sokolov,Kaledin,Nikolin,Popova,Patel,Zakharova,Chepanova,Zafar,Reynisson,Leung,Leung,Volcho,Salakhutdinov,Lavrik
, p. 581 - 593 (2018/11/10)
The druggability of the tyrosyl-DNA phosphodiesterase 1 (Tdp1) enzyme was investigated in conjunction with topoisomerase 1 inhibition. A novel class of thiazole, aminothiazole and hydrazonothiazole usnic acid derivatives was synthesized and evaluated as Tdp1 inhibitors and their ability to sensitize tumors to topotecan, a topoisomerase inhibitor in clinical use. Of all the compounds tested, four hydrazinothiazole derivatives, 20c, 20d, 20h and 20i, inhibited the enzyme in the nanomolar range. The activity of the compounds was verified by affinity experiments as well as supported by molecular modelling. The most effective Tdp1 inhibitor, 20d, was ton-toxic and increased the effect of topotecan both in vitro and in vivo in the Lewis lung carcinoma model. Furthermore, 20d showed significant increase in the antitumor and antimetastatic effect of topotecan in mice. The results presented here justify compound 20d to be considered as a drug lead for antitumor therapy.
Structure-Based Discovery of Thiosemicarbazone Metalloproteinase Inhibitors for Hemorrhage Treatment in Snakebites
Ferreira, Francis B.,Pereira, Thiago M.,Souza, Dayane L. N.,Lopes, Daiana S.,Freitas, Vitor,ávila, Veridiana M. R.,Kümmerle, Arthur E.,Sant'Anna, Carlos Mauricio R.
supporting information, p. 1136 - 1141 (2017/11/15)
The venoms of snakes are composed by many toxins, which are responsible for various toxic effects including intense pain, bleeding disorders, and local tissue damage caused by hemorrhage and necrosis. The snake venom metalloproteinases (SVMPs) are proteolytic zinc-dependent enzymes acting in different hemostatic mechanisms. In this work, a structure-based molecular modeling strategy was used for the rational design, by means of a homology 3D model of an SVMP isolated from Bothrops pauloensis venom (BpMP-I), followed by synthesis and in vitro evaluation of new thiosemicarbazones as the first inhibitors of the B. pauloensis SVMP. Besides being effective for the SVMP inhibition, two molecules were shown to be effective also in vivo, inhibiting hemorrhage caused by the B. pauloensis whole venom. Docking studies on metalloproteinases from other snake species suggest that the thiosemicarbazones activity is not confined to BpMP-I, but seems to be a common feature of metzincins.
