TF--a novel cell-permeable and selective inhibitor of human protein kinase CK2 induces apoptosis in the prostate cancer cell line LNCaP.

Background: Abnormally high activity of protein kinase CK2 is linked to various diseases including cancer. Therefore, the inhibition of CK2 is a promising therapeutic strategy to fight this disease.

Methods: We screened a library of synthetic molecules concerning their capacity to inhibit CK2.

A novel application of DDQ as electrophile in the Nenitzescu reaction.

Reaction of 2,3-dichloro-5,6-dicyano-benzoquinone (DDQ) with secondary enaminones yields surprisingly 2-aza-spiro[4,5]decatrienes. The reaction occurs via cyclisation of the primary Michael-adduct with the nitrile group. Reaction of DDQ with tertiary and also certain secondary enamines leads to 3-amino-benzo[b]furan derivatives.

A new 4-nitrobenzyl carbonate prodrug of methyl 5-benzyl-2-hydroxy-11-methylene-6-oxo-5H-benzo[b]carbazole-1-carboxylate for potential use with nitroreductase-based gene-directed enzyme prodrug therapy (GDEPT).

A tumour-selective 4-nitrobenzyloxycarbonyl prodrug methyl 5-benzyl-2-hydroxy-11-methylene-6-oxo-5H-benzo[b]carbazole-1-carboxylate was synthezised for gene-directed enzyme prodrug therapy (GDEPT). The compound is a substrate for E. coli nitroreductase.

1,4,9,10-Anthradiquinone as precursor for antitumor compounds.

1,4,9,10-Anthradiquinone 5 was reacted with enamines 6 in the Nenitzescu reaction to yield unexpected 3,3a,6,12-tetrahydro-3a,7-dihydroxy-2-methyl-6,12-dioxo-naphtho[2,3-d]indol-1-carboxylates 8A. However, anthracycline-like naphtho-condensed 5-hydroxyindoles were not obtained from this diquinone. It yielded similar reaction products of the Nenitzescu reaction like other quinones activated by two electron-withdrawing groups.

Synthesis, antitumour activity and structure-activity relationships of 5H-benzo[b]carbazoles.

A series of novel 5H-benzo[b]carbazoles related to the ellipticines was obtained from the reactions of p-benzoquinones with 2-aminomethylene-1-indanones. Most of the compounds were evaluated for their antitumour activity in the National Cancer Institute's in vitro human tumour cell line screening panel. Among them, particularly derivative 15c bearing a p-quinone methide moiety in ring C of the heterocycle was found to show in vitro activity comparable to clinically well established anticancer agents such as amsacrine or mitomycin C.