TY - JOUR
T1 - Biological activities of novel derivatives of differentiation-inducing factor 3 from Dictyostelium discoideum
AU - Takahashi, Katsunori
AU - Kikuchi, Haruhisa
AU - Nguyen, Van Hai
AU - Oshima, Yoshiteru
AU - Ishigaki, Hirotaka
AU - Nakajima-Shimada, Junko
AU - Kubohara, Yuzuru
N1 - Funding Information:
Acknowledgments This work was supported in part by Grants from the Japan Society for the Promotion of Science (JSPS) KAKENHI (no. 15K07964 to YO and YK; no. 16H03279 to HK); the Platform Project for Support in Drug Discovery and Life Science Research from the Japan Agency for Medical Research and Development (AMED) (to HK and YO); the Shorai Foundation for Science and Technology (to HK); the Kobayashi International Scholarship Foundation (to HK); and the Takeda Science Foundation (to HK).
Publisher Copyright:
© 2017 The Pharmaceutical Society of Japan.
PY - 2017
Y1 - 2017
N2 - Differentiation-inducing factor-3 (DIF-3; 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one), which is found in the cellular slime mold Dictyostelium discoideum, is a potential candidate compound for the development of new medicines; DIF-3 and its derivatives possess several beneficial biological activities, including anti-tumor, anti-Trypanosoma cruzi, and immunoregulatory effects. To assess the relationship between the biological activities of DIF-3 and its chemical structure, particularly in regard to its alkoxy group and the length of the alkyl chains at the acyl group, we synthesized two derivatives of DIF-3, 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)octan-1-one (DIF-3(+3)) and 1-(3-chloro-2,6-dihydroxy-4-butoxyphenyl)-hexan- 1-one (Hex-DIF-3), and investigated their biological activities in vitro. At micro-molar levels, DIF-3(+3) and Hex-DIF-3 exhibited strong anti-proliferative effects in tumor cell cultures, but their anti-T. cruzi activities at 1 μM in vitro were not as strong as those of other known DIF derivatives. In addition, Hex-DIF-3 at 5 μM significantly suppressed mitogen-induced interleukin-2 production in vitro in Jurkat T cells. These results suggest that DIF-3(+3) and Hex-DIF-3 are promising leads for the development of anti-cancer and immunosuppressive agents.
AB - Differentiation-inducing factor-3 (DIF-3; 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one), which is found in the cellular slime mold Dictyostelium discoideum, is a potential candidate compound for the development of new medicines; DIF-3 and its derivatives possess several beneficial biological activities, including anti-tumor, anti-Trypanosoma cruzi, and immunoregulatory effects. To assess the relationship between the biological activities of DIF-3 and its chemical structure, particularly in regard to its alkoxy group and the length of the alkyl chains at the acyl group, we synthesized two derivatives of DIF-3, 1-(3-chloro-2,6-dihydroxy-4-methoxyphenyl)octan-1-one (DIF-3(+3)) and 1-(3-chloro-2,6-dihydroxy-4-butoxyphenyl)-hexan- 1-one (Hex-DIF-3), and investigated their biological activities in vitro. At micro-molar levels, DIF-3(+3) and Hex-DIF-3 exhibited strong anti-proliferative effects in tumor cell cultures, but their anti-T. cruzi activities at 1 μM in vitro were not as strong as those of other known DIF derivatives. In addition, Hex-DIF-3 at 5 μM significantly suppressed mitogen-induced interleukin-2 production in vitro in Jurkat T cells. These results suggest that DIF-3(+3) and Hex-DIF-3 are promising leads for the development of anti-cancer and immunosuppressive agents.
KW - Anti-tumor agent
KW - Dictyostelium discoideum
KW - Interleukin-2
KW - Jurkat cell
KW - Trypanosoma cruzi
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U2 - 10.1248/bpb.b17-00484
DO - 10.1248/bpb.b17-00484
M3 - Article
C2 - 29093342
AN - SCOPUS:85034051826
SN - 0918-6158
VL - 40
SP - 1941
EP - 1947
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
IS - 11
ER -
