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.

Leccinum vulpinum Watling induces DNA damage, decreases cell proliferation and induces apoptosis on the human MCF-7 breast cancer cell line

The current work aimed to study the antitumour activity of a phenolic extract of the edible mushroom Leccinum vulpinum Watling, rich essentially in hydroxybenzoic acids. In a first approach, the mushroom extract was tested against cancer cell growth by using four human tumour cell lines. Given the positive results obtained in these initial screening experiments and the evidence of some studies for an inverse relationship between mushroom consumption and breast cancer risk, a detailed study of the bioactivity of the extract was carried out on MCF-7 cells. Once the selected cell line to precede the work was the breast adenocarcinoma cell line, the human breast non-malignant cell line MCF-10A was used as control. Overall, the extract decreased cellular proliferation and induced apoptosis. Furthermore, the results also suggest that the extract causes cellular DNA damage. Data obtained highlight the potential of mushrooms as a source of biologically active compounds, particularly with antitumour activity.