New 9-Terpenyl(7-Terpenyl)Purines: synthesis and cytotoxicity

The purine ring system is one of the most widely distributed N-heterocycles in Nature [1] and many structurally modified purine nucleosides and nucleotides have activities ranging from antineoplastic and antiviral to antihypertensive, antiasthmatic, antituberculosis, etc [2]. Among the purine derivatives, we have put our attention on natural N-alkylpurines such as the asmarines or agelasimines, a group of secondary metabolites isolated from marine sponges with very interesting biological properties [3]. They have a diterpenoid moiety attached to the N-7 nitrogen atom of an adenine and are usually isolated in very small quantities, which limited their structure-activity relationship studies. Our research group has been involved for years in the design, synthesis and biological evaluation of cytotoxic compounds related to natural products, including the chemoinduction of bioactivity on inactive terpenoids [4]. These diterpenoid include compounds such as communic or cupressic acids that bear decaline moieties very close to those present in the above-mentioned marine natural products. These facts prompted us to design and prepare new terpenylpurine derivatives starting from natural monoterpenoids and diterpenoids, commercially available or isolated from their natural sources and transformed into appropriate alkylated agents. Thus, we have prepared purines alkylated at N-7 and N-9 positions with isoprenoids, monoterpenoids and diterpenoids, using two different synthetic approaches: from 6-chloropurine or from 4,5-diamine-6-chloropyrimidine. The structure of the synthesized purines are shown in the following figure. The purine analogues synthesized have been evaluated for their cytotoxicity against four tumour human cell lines (breast, non-small lung, cervical and hepatocellular carcinoma) and non-tumour cells (porcine liver primary cells). The most cytotoxic derivatives were those with a diterpenoid rest on the purine. The results obtained allowed to draw conclusions on the structure-activity relationship of the compounds in order to evaluate the influence of the terpenyl size on their cytotoxic properties.

Synthesis of waterborne polyurethane-urea dispersions with chain extension step in homogeneous and heterogeneous media

Hypothesis: The possibility of tailoring the final properties of environmentally friendly waterborne polyurethane and polyurethane-urea dispersions and the films they produce makes them attractive for a wide range of applications. Both the reagents content and the synthesis route contribute to the observed final properties. Experiments: A series of polyurethane-urea and polyurethane aqueous dispersions were synthesized using 1,2-ethanediamine and/or 1,4-butanediol as chain extenders. The diamine content was varied from 0 to 4.5 wt%. Its addition was carried out either by the classical heterogeneous reaction medium (after phase inversion step), or else by the alternative homogeneous medium (prior to dispersion formation). Dispersions as well as films prepared from dispersions have been later extensively characterized. Findings: 1,2-Ethanediamine addition in heterogeneous medium leads to dispersions with high particle sizes and broad distributions whereas in homogeneous medium, lower particle sizes and narrow distributions were observed, thus leading to higher uniformity and cohesiveness among particles during film formation. Thereby, stress transfer is favored adding the diamine in a homogeneous medium; and thus the obtained films presented quite higher stress and modulus values. Furthermore, the higher uniformity of films tends to hinder water molecules transport through the film, resulting, in general, in a lower water absorption capacity.