Synthesis of novel (Z)‐methyl‐12‐aminooctadec‐9‐enoate‐based phenolipids as potential antioxidants and chemotherapeutic agents

A series of novel phenolipids were synthesized by coupling (Z)‐methyl‐12‐aminooctadec‐9‐enoate with substituted aromatic phenolic acids. The substrate (Z)‐methyl‐12‐aminooctadec‐9‐enoate was synthesized from methyl ricinoleate employing a four‐step procedure. The synthesized phenolipids were thoroughly characterized by FT‐IR, ¹H NMR, ¹³C NMR, ESI‐MS, and HRMS spectral analysis. The in vitro antioxidant activities of synthesized compounds were evaluated by 2, 2‐diphenyl‐1‐picrylhydrazyl radical (DPPH•), superoxide free radical scavenging activity, and lipid peroxidation inhibitory activities. The novel phenolic compounds were compared in terms of antioxidant activity with the commercial antioxidants, namely butylated hydroxy toluene (BHT) and α‐tocopherol as reference compounds. The antioxidant screening data of all the synthesized compounds revealed that DPPH free radical scavenging activity, superoxide, and lipid peroxidation inhibitory activity of caffeic and gallic acid substituted phenolipids exhibited excellent activity as compared to commercial antioxidants, BHT, and α‐tocopherol. The synthesized phenolipids were also evaluated for anticancer activities against four different cancer cell lines namely DU145, HePG2, SKOV3, MDA‐MB‐231. Among these compounds, 7a, 7b, 7d, 7e which were derived from cinnamic acid‐based phenolic acids and 8b which is derived from vanillic acid exhibited good anticancer activity against the tested cell lines. Practical applications: Lipophilization of phenolic acids improves their antioxidant and anticancer properties. The (Z)‐methyl‐12‐aminooctadec‐9‐enoate‐based phenolipids can be exploited in a number of lipophilic antioxidant and anticancer formulations. A panel of (Z)‐methyl‐12‐aminooctadec‐9‐enoate‐based phenolipids are synthesized for the first time from methyl ricinoleate, an unusual fatty acid isolated from castor oil. These compounds were evaluated for antioxidant properties, and gallic and caffeic acid‐based phenolipids exhibited extraordinary properties compared to BHT and α‐tocopherol commercially available antioxidants used in food and pharmaceutical formulations. These compounds were evaluated for anticancer activity for the first time, where these have exhibited good to moderate activity. Hence, (Z)‐methyl‐12‐aminooctadec‐9‐enoate‐based phenolipids can be exploited in a number of lipophilic antioxidant and anticancer formulations.