Bioassay-Guided Isolation and Evaluation of Antiproliferative Effects of (Z)-Ethylidene-4, 6-Dimethoxycoumaran-3-One from Pogostemon Quadrifolius (Benth.)

Abstract

<br /> <span style="font-size: small;">The aim of the study was to isolate and identify the major cytotoxic principle from plant leaves of </span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Pogostemon quadrifolius </span></span></em><span style="font-size: small;">(Benth.) and evaluate its antiproliferative potential against human cancer cells. Plant leaves were extracted sequentially with a soxhlet apparatus, using petroleum ether, chloroform and methanol solvents. Petroleum ether and chloroform extracts exhibited antiproliferative properties against Caco-2, HeLa, THP-1, MCF-7 and Jurkat E6-1cancer cell lines tested, but methanol extracts failed to exhibit such activity. The major antiproliferative principle from petroleum ether and chloroform extracts was isolated with the help of bioassay guided column chromatography. This cytotoxic </span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">compound was further analysed by UV, TLC, HPLC, LC-MS, GC-MS and NMR analyses and was identified to be </span></span><span style="font-size: small;">novel: (</span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Z</span></span></em><span style="font-size: small;">)-ethylidene-4,6-dimethoxycoumaran-3-one (Compound 1). The half-maximal inhibitory concentrations for proliferation (IC</span><span style="font-size: xx-small;">50</span><span style="font-size: small;">) exhibited by compound 1 were 19.4, 23.1, 22.1, 35.9 and 8.32 μM against Caco-2, HeLa, THP-1, MCF-7 and Jurkat E6-1 cancer cell lines, respectively. Further experiments revealed that compound 1 triggered the </span><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">apoptosis mode of cell death in cancer cell lines. Thus, the present study allowed isolation and identification of a </span></span><span style="font-size: small;">novel cytotoxic natural compound, (</span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">Z</span></span></em><span style="font-size: small;">)-ethylidene-4,6-dimethoxycoumaran-3-one, from plant leaves of </span><em><span style="font-family: Times New Roman,Times New Roman; font-size: small;"><span style="font-family: Times New Roman,Times New Roman; font-size: small;">P. quadrifolius </span></span></em><span style="font-size: small;">(Benth.). Our pre-clinical study also indicated that compound 1 is particularly active in the acute T cell leukemia cell line (Jurkat E6-1) with potential for application as a chemotherapeutic agent in the future. </span>