Enhancing Macrocyclic Diterpenes as Multidrug-Resistance Reversers: Structure–Activity Studies on Jolkinol D Derivatives

The phytochemical study of Euphorbia piscatoria yielded jolkinol D (1) in a large amount, whose derivatization gave rise to 12 ester derivatives (2–13) and hydrolysis to compound 14. The in vitro modulation of P-gp of compounds 1–14 was evaluated through a combination of transport and chemosensitivity assays, using the L5178 mouse T lymphoma cell line transfected with the human MDR1 gene. Apart from jolkinol D, all derivatives (2–14) showed potential as MDR reversal agents. In this small library of novel bioactive macrocyclic lathyrane diterpene derivatives, designed to evaluate structure–activity relationships essential in overcoming multidrug resistance (MDR), some correlations between MDR reversal and molecular weight, accessible solvent areas, and octanol/water partition coefficient were identified that can contribute to the development of new selective P-gp reversal agents.

Libraries and Canon-Formation: the Case of English in the Collections of the Library of the Faculty of Humanities, Lisbon University

Abstract: The project for researching the role played by libraries in canon-formation (namely through their policies regarding the creation, organization, preservation, and utilization of the collections) will be presented and discussed. We selected the Library of the Faculty of Humanities, Lisbon University, a modern academic library, created in 1859, by royal decree of D. Pedro V, following his canonical choice. Actually, the two contemporary rulers of new Britannia— Prince Albert, his cousin, and Queen Victoria—held this king in high consideration for his outstanding contribution to Portuguese modernisation. Representing various fields of study, the collections were decisive to canon-formation in the Faculty of Humanities. Thus, we have been trying to answer the following questions: who has been creating, organizing, preserving, and utilizing the collections, from the mid-nineteenth century onwards? When, where and how? Presently, we are studying the collections in English, namely the works belonging or referring to the long nineteenth century. Richard Garnett’s “The International Library of Famous Literature” (London, 1899) is our first case-study. The anthology determined the Western literary, cultural and visual canon at the turning of the century, as evidenced by comparing it to the Portuguese and Spanish editions, published at the beginning of the twentieth century.