Synthesis, molecular docking with CXCR4 and pharmacokinetic/toxicity prediction study of new analogues myristicyl ester

Abstract

This study aims to synthesise and characterise a series of new myristicyl esters analogues using a combination of Nuclear Magnetic Resonance (NMR) and Mass Spectrometry (MS). Myristicyl ester compounds, namely 7-methoxybenzo[d][1,3]dioxol-5-ylmethyl butanoate (E1), 7-methoxy-benzo[d][1,3]dioxol5-ylmethyl isobutanoate (E2), 7-methoxy-benzo[d][1,3]dioxol-5-ylmethyl pentanoate (E3), and 7-methoxy-benzo[d][1,3]dioxol-5-ylmethyl isopentanoate (E4) were prepared from the reaction between 7-methoxy-benzo[d][1,3]dioxol-5- ylmethanol with acyl chloride. The results showed that the yield of the compounds ranged from 61.6 to 69.7%. In silico molecular docking studies with CXCR4 indicated that E1-E4 had anti-inflammatory potential. Meanwhile, pharmacokinetic and toxicity predictions using pKCSM and Protox showed that E1-E4 complied with Lipinski's rule, with good bioavailability and very low toxicity (LD50 >2000 mol/kg). Despite these results, further in vitro and in vivo studies are needed to support the predictions.