Abstract
Vitamin K is the collective term for compounds that share a 2-methyl-1,4-naphthoquinone ring, but differ in the side-chain at the 3-position. We synthesized novel 2-methyl-1,4-naphthoquinone derivatives with different side chain length at the 3-position. Derivatives with C-14 and C-16 tails showed the highest in vitro bioactivity resulting in 2.5 and 2-fold higher carboxylated osteocalcin synthesis in MG63 cells than menaquinone-4 (MK-4, form of vitamin K2). Longer side chain lengths resulted in lower bioactivity. The in vivo vitamin K activity of the C-14 tail derivative was further tested in WRY rats receiving a vitamin IC-deficient diet that resulted in a 40% decrease of prothrombin activity. The C-14 tail derivative was able to counteract the effects on vitamin K deficiency induced by the diet and resulted in the complete restoration of prothrombin activity. Compared to naturally occurring forms of vitamin K, synthetic vitamin K derivatives may have higher bioactivity and different pharmacological characteristics that are more favorable for use as supplements or in clinical settings. (C) 2016 Elsevier Ltd. All rights reserved.
Original language | English |
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Pages (from-to) | 208-211 |
Number of pages | 4 |
Journal | Bioorganic & Medicinal Chemistry Letters |
Volume | 27 |
Issue number | 2 |
DOIs | |
Publication status | Published - 15 Jan 2017 |
Keywords
- 2-Methyl-1,4-naphthoquinone
- Vitamin K
- Phylloquinone
- Menaquinone
- Osteocalcin
- VITAMIN-K
- PROTHROMBIN
- ACID
- PHYLLOQUINONE
- ANALOGS
- MATRIX
- FOOD