Synthesis and antileukemic activities of C1–C10-modified parthenolide analogues

• Published in: Bioorganic & medicinal chemistry Vol. 23; no. 15; pp. 4737 - 4745
• Main Authors: Kempema, Aaron M., Widen, John C., Hexum, Joseph K., Andrews, Timothy E., Wang, Dan, Rathe, Susan K., Meece, Frederick A., Noble, Klara E., Sachs, Zohar, Largaespada, David A., Harki, Daniel A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.08.2015; Elsevier
• Subjects: Acute myeloid leukemia; Alkenes - chemistry; Animals; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biochemistry & Molecular Biology; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Bone Marrow Cells - metabolism; Bone marrow toxicity; Cell Line, Tumor; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Crystallography, X-Ray; Cyclopropanation; Drug Design; Drug Screening Assays, Antitumor; Humans; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - mortality; Life Sciences & Biomedicine; Mice; Molecular Conformation; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Parthenolide; Pharmacology & Pharmacy; Physical Sciences; Reactive Oxygen Species - metabolism; Science & Technology; Sesquiterpene lactone; Sesquiterpenes - chemical synthesis; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; PtO2; LogD; PTL; BM; AraC; MTS; IMDM; DMEM; CSC; FBS; SL; HSC; Bone marrow toxicity; Sesquiterpene lactone; LSC; DME; SFEM; AML; MelB; DOX; Cyclopropanation; MEM; HEPES; ROS; CTL; Parthenolide; Acute myeloid leukemia; DMAPT; CANCER-CELLS; STEM-CELLS; ACUTE MYELOID-LEUKEMIA; DRUG-RESISTANCE; ANTICANCER; AGENTS; SESQUITERPENE LACTONE PARTHENOLIDE; NF-KAPPA-B; DERIVATIVES; EXPRESSION

[Display omitted] Parthenolide (PTL) is a sesquiterpene lactone natural product with anti-proliferative activity to cancer cells. Selective eradication of leukemic stem cells (LSCs) over healthy hematopoietic stem cells (HSCs) by PTL has been demonstrated in previous studies, which suggests PTL and...