Inhibition of cancer cell invasion by new ((3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide analogs

Seong Mook Kang, Ky Youb Nam, Seung Youn Jung, Kyung Hee Song, Seongho Kho, Kyoung Tai No, Hyun Kyung Choi, Jie Young Song

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Rab GTPases regulate various types of intracellular membrane trafficking in all eukaryotes. Since Rab27a and its multiple effectors are involved in exocytosis of lysosome-related organelles and play a major role in malignancy, compounds targeting Rab27a could be likely used to inhibit invasive growth and tumor metastasis. Thus, we designed and synthesized several compounds based on the previously reported Rab27a-targeting synthetic compounds identified by virtual screening, and investigated their anti-metastatic effects in MDA-MB231 and A375 cells. Among the synthesized compounds, (E)-N-(3-chlorophenyl)-6-(2-(3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide (3d) and (E)-N-benzyl-6-(2-(3,4-dihydroxy benzylidene)hydrazinyl)-N-methylpyridine-3-sulfonamide (3f) significantly inhibited the invasiveness of both tumor cell lines. Compounds 3d and 3f also decreased the levels of signature extracellular matrix marker proteins (fibronectin, collagen, and α-smooth muscle actin) and representative mesenchymal cell markers (N-cadherin and vimentin). Taken together, our results suggest that novel sulfonamide analogs have anti-metastatic activity in breast and melanoma cancer cell lines and may be used as therapeutic agents to treat malignant cancer.

Original languageEnglish
Pages (from-to)1322-1328
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number4
DOIs
Publication statusPublished - 2016 Feb 15

Bibliographical note

Funding Information:
This work was supported by the Nuclear R&D Program of the Ministry of Science, ICT and Future Planning , Republic of Korea (Grant No. 1711021781 ).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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