Synthesis of novel ricinoleic acid-based 1, 2, 3-triazoles and their anticancer activity

Ricinoleic acid based triazoles as anticancer agents

Abstract

A series of novel chiral 1, 4-disubstituted 1H-1, 2, 3-triazole derivatives 8(a-i) has been accomplished using (Z)-methyl-12-azidooctadec-9-enoate, which is a derivative of castor oil fatty acid ester, methyl ricinoleate. The 1, 2, 3-triazole analogues were synthesized regioselectively by the Cu-catalysed azide-alkyne cycloaddition (CUAAC) via Huisgen “Click Chemistry”. The target 1, 2, 3-triazole derivatives' structure was characterized by FT-IR, ¹HNMR, ¹³CNMR, and Mass Spectral Studies. The dipole moment of the triazole derivatives exhibited 4.8-5.6 Debye units, indicating their stability towards different environments. The synthesized compounds 8 (a-i) were evaluated for their anticancer activity against four different cancer cell lines such as human lung cancer cell line (A549), human cervical cancer cell line (HeLa), human prostate cancer cell line (DU145), and human breast cancer cell line (MDA-MB-231) and doxorubicin was used as a standard reference drug.  All the compounds exhibited moderate anticancer activity except compound 8g bearing phenylalanine against the four cancer cell lines. Among these compounds, 8c, i.e., valine substituted-1, 2, 3-triazole displayed superior anticancer activity against A549 (IC₅₀, 12.3 ± 0.24µM); DU145 (IC₅₀, 15.6±0.24µM); MDA-MB-231 (IC_50, 17.8±0.20µM) cancer cell line compared to the other tested compounds. Further, the triazole derivatives were found to be quite safe towards the normal cell, as they did not exhibit any activity towards HLF-Human lung fibroblast.