34955-25-4Relevant articles and documents
Structural revision of the Mcl-1 inhibitor MIM1: synthesis and biological studies on ovarian cancer cells with evaluation of designed analogues
Bignon, Jér?me,Brotin, Emilie,Denoyelle, Christophe,El Dine, Assaad Nasr,Elie, Nicolas,Grée, René,Hachem, Ali,Hedir, Siham,Jouanne, Marie,Justaud, Frédéric,Levoin, Nicolas,Paysant, Hippolyte,Poulain, Laurent,Roisnel, Thierry,Roussi, Fanny,Soulieman, Ali,Tasseau, Olivier,Voisin-Chiret, Anne Sophie,Weiswald, Louis Bastien
, p. 8968 - 8987 (2021/11/04)
In the area of cancer research, the development of new and potent inhibitors of anti-apoptotic proteins is a very active and promising topic. The small molecule MIM1 has been reported earlier as one of the first selective inhibitors of the anti-apoptotic protein Mcl-1. In the present paper, we first revised the structure of this molecule based on extensive physicochemical analyses. Then we designed and synthesized a focused library of analogues for the corrected structure of MIM1. Next, these molecules were subjected to a panel ofin cellulobiological studies, allowing the identification of dual Bcl-xL/Mcl-1 inhibitors, as well as selective Mcl-1 inhibitors. These results have been complemented by fluorescence polarization assays with the Mcl-1 protein. Preliminary structure-activity relationships were discussed and extensive molecular modelling studies allowed us to propose a rationale for the biological activity of this series of new inhibitors, in particular for the selectivity of inhibition of Mcl-1versusBcl-xL
Synthesis of thiophene-thiosemicarbazone derivatives and evaluation of their in vitro and in vivo antitumor activities
De Oliveira, Jamerson Ferreira,Da Silva, Anekécia Lauro,Vendramini-Costa, Débora Barbosa,Da Cruz Amorim, Cezar Augusto,Campos, Júlia Furtado,Ribeiro, Amélia Galdino,De Moura, Ricardo Olímpio,Neves, Jorge Luiz,Ruiz, Ana Lúcia Tasca Gois,De Carvalho, Jo?o Ernesto,Alves De Lima, Maria Do Carmo
, p. 148 - 156 (2015/10/29)
A series of thiophene-2-thiosemicarbazones derivatives (5-14) was synthesized, characterized and evaluated for their antitumor activity. They were tested in vitro against human tumor cell lines through the colorimetric method. The results revealed that compounds 7 and 9 were the most effective in inhibiting 50% of the cell growth after 48 h of treatment. As compound 7 showed a potent antiproliferative profile, it has been chosen for further studies in 786-0 cell line by flow cytometry. Treatments with compound 7 (50 μM) induced early phosphatidylserine exposure after 18 h of exposure and this process progressed phosphatidylserine exposure with loss of cell membrane integrity after 24 h of treatment, suggesting a time-dependent cell death process. Regarding the cell cycle profile, no changes were observed after treatment with compound 7 (25 μM), suggesting a mechanism of cell death independent on the cell cycle. The in vivo studies show that compound 7 possess low acute toxicity, being the doses of 30-300 mgKg-1 chosen for studies in Ehrlich solid tumor model in mice. All doses were able to inhibit tumor development being the lowest one the most effective. Our findings highlight thiophene-2-thiosemicarbazones as a promising class of compounds for further studies concerning new anticancer therapies.
2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents
Klayman,Bartosevich,Griffin,Mason,Scovill
, p. 855 - 862 (2007/10/04)
Based on the antimalarial properties observed for 2-acetylpyridine 4-phenyl-3-thiosemicarbazone (1), an extensive series of related thiosemicarbazones was prepared and tested against Plasmodium berghei in mice. Screening results indicated that the presence of the 2-pyridylethylidene group was critical and that certain phenyl, benzyl, phenethyl, or cycloalkyl groups at N4 of the thiosemicarbazone moiety also contribute to antimalarial activity.
