Synthesis, molecular docking and Brugia malayi thymidylate kinase (BmTMK) enzyme inhibition study of novel derivatives of [6]-shogaol

•Twelve novel derivatives of [6]-shogaol have been synthesized.•5 compounds showed potential Brugia malayi thymidylatekinase inhibition activity.•Binding conformation of parent compound and its derivatives were consistent with the TMP bound conformation.

[6]-Shogaol (1) was isolated from Zingiber officinale. Twelve novel compounds have been synthesized and evaluated for their Brugia malayi thymidylate kinase (BmTMK) inhibition activity, which plays important role for the DNA synthesis in parasite. [6]-Shogaol (1) and shogaol with thymine head group (2), 5-bromouracil head group (3), adenine head group (4) and 2-amino-3-methylpyridine head group (5) showed potential inhibitory effect on BmTMK activity. Further molecular docking studies were carried out to explore the putative binding mode of compounds 1–5.

Graphical abstractTwelve novel derivatives of [6]-shogaol have been synthesized and screened for Brugia malayi thymidylatekinase (BmTMK) inhibition activity. Five compounds showed potential inhibitory effect on BmTMK activity. Molecular docking studies were carried out to explore the putative binding mode of compounds 1–5.Figure optionsDownload full-size imageDownload as PowerPoint slide