title: Inhibition of cancer cell invasion by new ((3,4-dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide analogs.
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.
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Seong-Mook
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Center for Development and Commercialization Anti-Cancer Therapeutics, Asan Medical Center, Seoul 138-736, Republic of Korea.
authors.forename: Ky-Youb
authors.initials: KY
authors.lastname: Nam
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Seung-Youn
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Song
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea.
authors.forename: Seongho
authors.initials: S
authors.lastname: Kho
authors.affiliation: Department of Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors.forename: Kyoung Tai
authors.initials: KT
authors.lastname: No
authors.affiliation: Department of Medicinal Chemistry, Jungwon University, Goesan 367-805, Republic of Korea. Electronic address: hkchoi45@jwu.ac.kr.
authors.forename: Hyun Kyung
authors.initials: HK
authors.lastname: Choi
authors.affiliation: Division of Radiation Cancer Research, Korea Institute of Radiological & Medical Sciences, Seoul 139-706, Republic of Korea. Electronic address: immu@kirams.re.kr.
authors.forename: Jie-Young
authors.initials: JY
authors.lastname: Song
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000075745:rab27 GTP-Binding Proteins
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D016326:Extracellular Matrix Proteins; D013449:Sulfonamides; D014746:Vimentin; D000075745:rab27 GTP-Binding Proteins; C066694:RAB27A protein, human; D020691:rab GTP-Binding Proteins
keywords: ((3,4-Dihydroxy benzylidene)hydrazinyl)pyridine-3-sulfonamide; Intracellular membrane trafficking; Invasion; Metastasis; Protein–protein blocker; Rab GTPases; Rab27a