Medicinal plants have been shown to have tremendous potential for the development of new drug molecules for various serious diseases. Piper nigrum L. (Piperaceae) is a well-known spice considered to be the “The King of Spices” among various spices. The phytochemicals isolated from P. nigrum L. are potent biological agents with anticancer properties. Our study was designed to evaluate the cytotoxic activities of chemical compounds from the dried fruits of P. nigrum L. Sixteen known compounds (1–16), including fifteen alkaloids, were isolated and identified. Compounds 10, 11, 12, 13, 14, and 15 exhibited cytotoxic activities against a human cervical cancer cell line, Hela, with IC50 values of 49.8, 40.4, 23.1, 22.1, 41.0, and 26.9 μM, respectively. Compounds 10, 12, and 15 exhibited cytotoxicities against a breast cancer cell line, MCF-7, with IC50 values of 36.9, 55.7, and 36.0 μM, respectively. Compounds 6, 12, 13, 14, 15, and 16 exhibited cytotoxic activities against the human promyelocytic leukemia cell line, HL-60, with IC50 values of 26.9, 51.4, 51.6, 54.4, 16.0, and 21.1 μM, respectively.
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