Structure–activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors. Issue 5 (1st March 2016)

• Record Type: Journal Article
• Authors: Ohno, Hiroaki; Minamiguchi, Daiki; Nakamura, Shinya; Shu, Keito; Okazaki, Shiho; Honda, Maho; Misu, Ryosuke; Moriwaki, Hirotomo; Nakanishi, Shinsuke; Oishi, Shinya; Kinoshita, Takayoshi; Nakanishi, Isao; Fujii, Nobutaka
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 5(2016)
• Page Start: 1136
• Page End: 1141
• Publication Date: 2016-03-01
• Subjects: Protein kinase CK2 -- Kinase inhibitor -- Structure–activity relationship -- Rational design; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.01.043
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine- and pyridazine-carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2α) = 0.014–0.017 μM; IC50 (CK2α′) = 0.0046–0.010 μM]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintained the potent CK2 inhibitory activities [IC50 (CK2α) = 0.014–0.016 μM; IC50 (CK2α′) = 0.0088–0.014 μM] and led to antiproliferative activities [CC50 (A549) = 1.5–3.3 μM] three to six times higher than those of the parent compound.