Cancer

Bioorganic & Medicinal Chemistry Letters 23 (2013) 6864–6867

Contents lists available at ScienceDirect

Bioorganic & Medicinal Chemistry Letters

journal homepage: www.elsevier.com/locate/bmcl

Antiproliferative activities and SAR studies of substituted

anthraquinones and 1,4-naphthoquinones

Deepak Bhasin  , Jonathan P. Etter  , Somsundaram N. Chettiar, May Mok, Pui-Kai Li ⇑

Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Rm 338 Parks Hall, 500 West 12th Avenue, Columbus, OH 43210-1291,

United States

a r t i c l e

i n f o

Article history:

Received 21 August 2013

Revised 25 September 2013

Accepted 30 September 2013

Available online 9 October 2013

Keywords:

STAT3 inhibitor

LLL3

LLL12

a b s t r a c t

STAT3 is constitutively active in a large variety of cancers. The search for STAT3 inhibitors led to the

discoveries of LLLs 3 and 12, which are substituted anthraquinones. LLL12 is an extremely potent

compound that exhibits high levels of antiproliferative activity. Herein the synthesis and evaluation of

compounds containing either an anthraquinone or 1,4-naphthoquinone moiety are reported. Analogs

were evaluated in several cancer cell lines. Interestingly, it was found that the anthraquinones did not

follow the same trends as the 1,4-naphthoquinones in regards to potency. LLL12, which contains a

sulfonamide at position 1, was found to be the most potent of the anthraquinones. In contrast, the methyl

ketone and methyl ester derivatives (LLLs 3.1 and 5.1) were found to be the most potent of the 1,

4-naphthoquinones. Selected 1,4-naphthoquinones were also evaluated in the STAT3 fluorescence

polarization assay in order to evaluate their abilities to bind to the STAT3 SH2 domain. They were found

to have similar affinities, and their activities suggest that STAT3 is one of their molecular targets.

Ó 2013 Elsevier Ltd. All rights reserved.

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