Artemisinin-Polypyrrole Conjugates: Synthesis, DNA Binding Studies and Preliminary Antiproliferative Evaluation

• Published in: ChemMedChem Vol. 8; no. 5; pp. 709 - 718
• Main Authors: La Pensée, Louise, Sabbani, Sunil, Sharma, Raman, Bhamra, Inder, Shore, Emma, Chadwick, Amy E., Berry, Neil G., Firman, James, Araujo, Nuna C., Cabral, Lília, Cristiano, Maria L. S., Bateman, Cerys, Janneh, Omar, Gavrila, Adelina, Wu, Yi Hang, Hussain, Afthab, Ward, Stephen A., Stocks, Paul A., Cosstick, Rick, O'Neill, Paul M.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.05.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Antineoplastic Combined Chemotherapy Protocols - chemical synthesis; Antineoplastic Combined Chemotherapy Protocols - chemistry; Antineoplastic Combined Chemotherapy Protocols - pharmacology; artemisinin; Artemisinins - chemistry; Artemisinins - pharmacology; Binding Sites - drug effects; binding studies; Cell Proliferation - drug effects; Chemistry, Medicinal; cytotoxicity; DNA; DNA - chemistry; DNA - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HL-60 Cells; HT29 Cells; Humans; Life Sciences & Biomedicine; Models, Molecular; Molecular Conformation; Molecular Dynamics Simulation; molecular modelling; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Plasmodium falciparum - drug effects; Polymers - chemistry; Polymers - pharmacology; Pyrroles - chemistry; Pyrroles - pharmacology; Science & Technology; Structure-Activity Relationship; Thermodynamics; NETROPSIN; DRUG; LIGAND EFFICIENCY; molecular modelling; DOCKING; MALARIA PARASITES; GENETIC ALGORITHM; artemisinin; EFFICIENCY INDEXES; DNA; ANTIMALARIAL ACTIVITY; binding studies; DERIVATIVES; cytotoxicity; MINOR-GROOVE
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201200536

Greater than the sum of its parts: Artemisinins are currently in phase I–II clinical trials against breast, colorectal and non‐small‐cell lung cancers. In an attempt to offer increased specificity, a series of hybrid artemisinin–polypyrrole minor groove binder conjugates are described. DNA binding/modelling studies and preliminary biological evaluation give insights into their mechanism of action and the potential of this strategy.