Indeno[1,2-b]indole derivatives as protein kinase CK2 inhibitors: comparison of in silico models for Tox prediction

Fouillet B, Nacereddine A, Lied LN, Bouaziz Z, Herfindal L, Marminon C, Bollacke A, Døskeland SO, Jose J, Le Borgne M

Abstract

Series of indeno[1,2-b]indole derivatives were synthetised as human protein casein kinase II (CK2) inhibitors [1-3]. Inhibition of CK2 is an attractive therapeutic target for cancer treatment (breast, glioblastoma, pancreas and leukaemia) [4-7]. Some of our best CK2 inhibitors constitute promising anti-leukemic agents for treatment (work in progress), both alone or in combination with other chemotherapeutic agents (e.g. Ara-C, daunorubicin, nutlin, DNA-intercalating agents, metabolic drugs). For further biological investigations (in vivo), the exploration of the ADMET profile of the most promising CK2 inhibitors is extremely important and especially their toxicity profile including mutagenicity, genotoxicity and developmental toxicity. In this study we propose to predict toxicity data for six CK2 inhibitors (emodin and silmitasertib as reference compounds) by using four open access softwares (OECD QSAR toolbox, CAESAR, TEST and TOXTREE QSAR [8]).