4‐Hydroxy Enigmol, a 1‐Deoxyphytosphingolipid that Exhibit Good Activity against Prostate and Colon Cancer

Abstract

AbstractIn the present work, 4‐hydroxy enigmol (1), an analogue of enigmol which is a known orally bioavailable 1‐deoxysphingolipid, effective against multiple cancer cell lines, has been synthesized with an additional hydroxy group for improved anti‐cancer activity. The additional group in compound (1) is likely to show enhanced activity due to improved cell permeability and hydrophilicity. The key steps involved are stereoselective cross metathesis reaction and OsO4/NMO mediated dihydroxylation. Further, analogues of 4‐hydroxy enigmol (1) with varying chain lengths (2, 3) have also been synthesized using the same synthetic strategy for varying hydrophobicity as an additional structural feature. To support the genesis in the design of compound (1–3), the pharmacokinetic studies and docking analysis has been done for calculating the polar surface area, binding affinity and hydrophobicity/hydrophilicity. The preliminary in‐vitro cytotoxicity on cancer cell lines displayed promising activity against the PC‐3 cell lines and HCT‐116 cell lines.