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Camptothecin Analogues (camptothecin + analogue)
Selected AbstractsSynthesis of New Camptothecin Analogues with the E-Lactone Ring Replaced by ,,,-CyclohexenoneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2006Valeriy A. Bacherikov Abstract The total synthesis of racemic camptothecin analogues 12a and 12b, in which the E-lactone ring has been replaced by an ,,,-cyclohexenone ring and the ethyl and hydroxy substituents have been retained, was achieved by first preparing the ABCD fragments 31a and 31b, which were then converted into the tetracyclic triol 36a and 36b by osmium-mediated dihydroxylation. Compounds 36a and 36b were oxidized in one-pot reactions, followed by intramolecular aldol condensation to furnish the desired pentacyclic 12a and 12b, which retained topoisomerase I inhibitory activity and exhibited cytotoxicity to tumor cell growth in culture.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Cascade [4 + 1] Radical Annulations of 2,6-Disubstituted Phenyl Isonitriles with N-Propargyl-6-iodopyridones: Scope, Mechanism and Regioselective Synthesis of 7,9-Disubstituted Camptothecin Analogues.CHEMINFORM, Issue 48 2003Wu Du Abstract For Abstract see ChemInform Abstract in Full Text. [source] Liposome transport of hydrophobic drugs: Gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2008Vijay Joguparthi Abstract The design of liposomal delivery systems for hydrophobic drug molecules having improved encapsulation efficiency and enhanced drug retention would be highly desirable. Unfortunately, the poor aqueous solubility and high membrane binding affinity of hydrophobic drugs necessitates extensive validation of experimental methods to determine both liposome loading and permeability and thus the development of a quantitative understanding of the factors governing the encapsulation and retention/release of such compounds has been slow. This report describes an efflux transport method using dynamic dialysis to study the liposomal membrane permeability of hydrophobic compounds. A mathematical model has been developed to calculate liposomal membrane permeability coefficients of hydrophobic compounds from dynamic dialysis experiments and partitioning experiments using equilibrium dialysis. Also reported is a simple method to study the release kinetics of liposome encapsulated camptothecin lactone in plasma by comparing the hydrolysis kinetics of liposome entrapped versus free drug. DB-67, a novel hydrophobic camptothecin analogue has been used as a model permeant to validate these methods. Theoretical estimates of DB-67 permeability obtained from the bulk solubility diffusion model and the "barrier-domain" solubility diffusion model are compared to the experimentally observed value. The use of dynamic dialysis in drug release studies of liposome and other nanoparticle formulations is further discussed and experimental artifacts that can arise without adequate validation are illustrated through simulations. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:400,420, 2008 [source] Synthesis of New Camptothecin Analogues with the E-Lactone Ring Replaced by ,,,-CyclohexenoneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2006Valeriy A. Bacherikov Abstract The total synthesis of racemic camptothecin analogues 12a and 12b, in which the E-lactone ring has been replaced by an ,,,-cyclohexenone ring and the ethyl and hydroxy substituents have been retained, was achieved by first preparing the ABCD fragments 31a and 31b, which were then converted into the tetracyclic triol 36a and 36b by osmium-mediated dihydroxylation. Compounds 36a and 36b were oxidized in one-pot reactions, followed by intramolecular aldol condensation to furnish the desired pentacyclic 12a and 12b, which retained topoisomerase I inhibitory activity and exhibited cytotoxicity to tumor cell growth in culture.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] | ||||||||||