Anti-proliferative Activities of Some Bivalent Symmetrical 5-Substituted Hydantoin Derivatives towards Human Brain Glioma U251 Cells (U251) and Human Carcinoma Cells (KB3-1)

• Published in: Biological & pharmaceutical bulletin Vol. 42; no. 11; pp. 1953 - 1956
• Main Authors: Furutachi, Makoto, Ota, Kaori, Fujisaki, Fumiko, Ikeda, Ryuji, Yoshikawa, Naoki, Yokota, Tsubasa, Takeda, Yasuo, Yokomizo, Kazumi, Zhou, Jian-Rong, Kashige, Nobuhiro, Miake, Fumio, Sumoto, Kunihiro
• Format: Journal Article
• Language: English; Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.11.2019; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: anti-proliferative activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biotechnology; Brain; Cell Line, Tumor; Cell Proliferation - drug effects; Cisplatin; cytotoxic activity; Glioma; Glioma cells; Humans; Hydantoin; Hydantoins - chemistry; Hydantoins - pharmacology; KB3-1 cell; Methylene; Molecular Structure; symmetrical bivalent molecule; U251 cell; anti-proliferative activity; cytotoxic activity; U251 cell; hydantoin; symmetrical bivalent molecule; KB3-1 cell
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b19-00486

Novel bivalent twin-drug type hydantoin derivatives were evaluated in vitro using a human brain glioma cell line (U251) and a human carcinoma cell line (KB3-1). Among the 5-substituted hydantoin derivatives (1a–b and 2a–d) examined in this study, bivalent symmetrical 5-substituted hydantoin derivative 1b showed the highest anti-proliferative activity towards both U251 and KB3-1 cells. The values of anti-proliferative activity (IC50) of this hydantoin derivative against the two cell lines (U251 and KB3-1) were 0.46 and 5.21 µM, respectively. The anti-proliferative activity of all of the compounds except for compounds 2a and 2d against U251 cells was higher than that of cisplatin. Bivalent symmetrical compound 1b had a biphenylmethane linker in the molecule. All of the tested bivalent hydantoin derivatives showed higher activity against U251 cells than against KB3-1 cells. For twin-drug type hydantoin derivatives 2a–d, which have a linear methylene linker in the molecules, it was found that methylene linker length in these molecules have an effect on the anti-proliferative activity against U251 and KB3-1 cells.