2. Academic Validation
  3. Synthesis and structure-activity relationship studies of naphthoquinones as STAT3 inhibitors

Synthesis and structure-activity relationship studies of naphthoquinones as STAT3 inhibitors

  • Bioorg Med Chem. 2023 Jul 15:90:117331. doi: 10.1016/j.bmc.2023.117331.
Mitsuaki Yamashita 1,  Yuto Nakamori 1,  Arisa Tsukamoto 1,  Nagisa Furuno 1,  Akira Iida 2
Affiliations

Affiliations

  • 1 School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan.
  • 2 School of Agriculture, Kindai University, Nakamachi, Nara 631-8505, Japan. Electronic address: iida@nara.kindai.ac.jp.
PMID: 37343498 DOI: 10.1016/j.bmc.2023.117331
Abstract

Based on previous studies, we synthesized a novel class of ortho- and para-naphthoquinones derivatives bearing a phenolic hydroxy or sulfonamide moiety and evaluated their in vitro antiproliferative and signal transducer and activator of transcription-3 (STAT3) phosphorylation inhibitory activities. The biological evaluations of these naphthoquinones revealed that ortho-naphthoquinones containing a phenolic hydroxyl group exhibited greater antiproliferative activity compared to compounds without a phenolic hydroxyl group. Among the synthesized para-naphthoquinones, 21, which has a condensed sulfonamide structure, showed substantially higher antiproliferative activity than that of the parent compound, and was also found to inhibit the phosphorylation of STAT3(Y705) in a dose-dependent manner. A docking simulation using AutoDock Vina suggested that 21 could directly bind to the hinge region of STAT3.

Keywords

Antiproliferative activities; Naphthoquinone; STAT3 inhibitory activities; Sulfonamide.

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