Aconitum C₂₀-diterpenoid alkaloid derivatives regulate the growth and differentiation of cord blood derived human hematopoietic stem/progenitor cells.
The pharmacological activity of Aconitum alkaloids depends on their fundamental structure. While C₁₉-norditerpenoid alkaloids present significant toxicity to the central nervous system, C₂₀-diterpenoid alkaloids have reduced toxicities. However, there is little information regarding the precise pharmacological properties of C₂₀-diterpenoid alkaloids. C₂₀-diterpenoid alkaloid derivatives have explicit structure-activity relationships targeting various tumor cells, which depend on the C11-substrate. However, the present study showed that C6-derivatives additively or synergistically sustained proliferation of CD34⁺ hematopoietic stem/progenitor cells derived from the placental/umbilical cord blood. It revealed that identical structures belonging to C₂₀-diterpenoid alkaloids surprisingly have opposing proliferative effects depending on the derivatization sites (C6 versus C11).
Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki, Aomori 036-8564, Japan.
Masaharu
M
Hazawa
Koji
K
Wada
Ikuo
I
Kashiwakura
D031841:Aconitum / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D018952:Antigens, CD34; D002454:Cell Differentiation; D049109:Cell Proliferation; D003470:Culture Media / Q000737:chemistry; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D013329:Structure-Activity Relationship
D000470:Alkaloids; D018952:Antigens, CD34; D003470:Culture Media; D004224:Diterpenes