Comparative metabolic study of Citrus sinensis leaves cultivars based on GC–MS and their cytotoxic activity

•Nine Citrus sinensis leaves cultivars in Egypt were analyzed via GC–MS.•47 metabolites were identified by GC–MS.•Monoterpenes hydrocarbons represented the main class in the essential oils.•PCA and HCA displayed successful discrimination between different cultivars.•All essential oils showed promising cytotoxic activity by MTT assay. Citrus sinensis L. Osbeck, (family Rutaceae), known as sweet orange, is a fruit-bearing shrub that widely cultivated all over the world due to its nutritive value, nutraceutical attributes and economic importance. In the present study, a comparative metabolic profile study of the essential oils of the leaves of nine cultivars of Citrus sinensis cultivated in Egypt was carried out based on GC–MS analysis coupled to chemometrics. A total of 47 compounds were identified, where monoterpenes hydrocarbons (61.39 %–78.26 %) represented the main recognized class in the essential oils. Sabinene (8.25 %–28.81 %), 2-carene (11.25 %–16.72 %) and cis-β-ocimene (10.22 %–13.93 %) were the major components identified in different cultivars. Chemometric analyses comprising Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were experienced for their ability to discriminate between closely related cultivars. Both PCA score plot and HCA dendrogram could successfully segregate different cultivars based on their metabolic profiles. The MTT assay was used to evaluate the cytotoxicity of essential oils of Citrus sinensis leaves cultivars on different cell lines; MCF-7, HepG-2, HeLa, were all essential oils showed moderate cytotoxic activity. The MCF-7 cell lines were the most resistant cells with IC50 range from 243 to 343 μg/mL, while HeLa cells were the most sensitive cell lines IC50 range from 203 to 283 μg/mL. This may be attributed to the synergistic effects of different chemical components.