Sesquiterpene lactones display a wide variety of biological effects such as antiviral, anti-inflammatory and cytotoxic activity. In previous studies some derivatives of sesquiterpene lactones were prepared to be tested as antiviral and/or cytoxic agents. In the present report we describe the effects of seven modified sesquiterpene lactones on the proliferation of several cancer cell lines. We demonstrated antitumoral activity of two of them: III (JLNZ-106) and IV (EDAG-IV-Sme) in HeLa, C-33, CALO, INBL, VIPA, SW480, SW620, MCF-7 and CHO cancer cell lines. Compounds III (JLNZ-106) and IV (EDAG-IV-Sme-IV) presented cytotoxic activity (IC50) by inhibiting the incorporation of (14)C-thymidine to DNA. These experiments suggest that derivatives III and IV should inhibit DNA replication in cancer cell lines.