Technical Evaluation of a New Medical Device Based on Rigenase in the Treatment of Chronic Skin Lesions.

Chronic wound is characterized by slow healing time, persistence, and abnormal healing progress. Therefore, serious complications can lead at worst to the tissue removal. In this scenario, there is an urgent need for an ideal dressing capable of high absorbency, moisture retention and antimicrobial properties. Herein we investigate the technical properties of a novel advanced non-woven triple layer gauze imbibed with a cream containing Rigenase, an aqueous extract of Triticum vulgare used for the treatment of skin injuries. To assess the applicability of this system we analyzed the dressing properties by wettability, dehydration, absorbency, Water Vapor Transmission Rate (WVTR), lateral diffusion and microbiological tests. The dressing showed an exudate absorption up to 50%. It created a most environment allowing a proper gaseous exchange as attested by the WVTR and a controlled dehydration rate. The results candidate the new dressing as an ideal medical device for the treatment of the chronic wound repairing process. It acts as a mechanical barrier providing a good management of the bacterial load and proper absorption of abundant wound exudate. Finally, its vertical transmission minimizes horizontal diffusion and side effects on perilesional skin as maceration and bacterial infection.

Endoperoxide derivatives from marine organisms: 1,2-dioxanes of the plakortin family as novel antimalarial agents.

Plakortin (1) is a remarkably simple 1,2-dioxane derivative, extracted from the marine sponge Plakortis simplex, showing a submicromolar activity against chloroquine-resistant strains of Plasmodium falciparum. Using plakortin as a novel antimalarial hit, we have prepared a series of semisynthetic derivatives in order to gain insights into the structural requirements of simple 1,2-dioxanes for exhibiting antimalarial activity. Their synthesis, spectroscopic and computational analysis, and in vitro antimalarial activity are herein reported. Results obtained, besides confirming the crucial role of the cycloperoxide functionality, revealed other structural features critical for antimalarial activity, namely the "Western" alkyl side chain, the dioxane ring conformation, and the absolute configuration of the stereogenic carbons on the 1,2-dioxane ring, when affecting the bioactive ring conformation.

A prenylbisabolane with NF-kappaB inhibiting properties from Cascarilla (Croton eluteria).

Investigation of the bark of Croton eluteria Bennett for biologically active compounds has led to the isolation of the new prenylbisabolane 3, whose structure was assessed by spectroscopic methods. The corresponding known enone 4 and the eudesmane sesquiterpene 2 were also obtained. Compound 3 proved active in selectively inhibiting the induction of NF-kappaB by tumor necrosis factor-alpha in T cells.

Coumarins from Opopanax chironium. New dihydrofuranocoumarins and differential induction of apoptosis by imperatorin and heraclenin.

Opopanax chironium is a rich source of furano- and dihydrofuranocoumarins, whose accumulation in all plant parts and especially the roots is presumably responsible for the poisonous properties of the species. The presence of two distinct chemotypes was evidenced, with the one from Sicily affording the new dihydrofuranocoumarins 5d and 5e, while extracts from the Sardinian chemotype showed powerful apoptotic activity, which was traced to the prenylated furanocoumarins heraclenin (2a) and imperatorin (2b). Despite a close structural similarity, compounds 2a and 2b induced apoptosis in Jurkat leukemia cells in mechanistically different ways.

Minor diterpenoids from cascarilla (Croton eluteria Bennet) and evaluation of the cascarilla extract and cascarillin effects on gastric acid secretion.

Three new diterpenoids belonging to the clerodane (2-3) and halimane (4) structural types have been isolated from the bark of Croton eluteria Bennet, commonly known as cascarilla. Their structures have been fully characterized by spectroscopic means. Cascarilla extract and its major component, cascarillin, were found to significantly increase histamine-induced gastric acid secretion in the mouse stomach. These preliminary results provide the first rationale for the use of cascarilla in bitter preparations aimed at improving digestion.

Simplakidine A, a unique pyridinium alkaloid from the Caribbean sponge plakortis simplex.

Simplakidine A, a unique 4-alkyl-substituted pyridiunium alkaloid, has been isolated from the Caribbean sponge Plakortis simplex. The stereostructure of simplakidine A has been determined using MS and NMR data, molecular mechanics, and an extension of the J-based configuration analysis. Data about the growth-inhibition activity of simplakidine A are reported.

Activity against Plasmodium falciparum of cycloperoxide compounds obtained from the sponge Plakortis simplex.

There is an urgent need to discover new antimalarials, due to the spread of chloroquine resistance and the limited number of available drugs. In the last few years, artemisinin, the endoperoxide sesquiterpene lactone derived from Artemisia annua, and its derivatives proved to be very active against Plasmodium falciparum. These compounds are characterized by an endoperoxide pharmacophore that is critical for their antimalarial activity. There are several reports, from our group and others, that marine organisms can be another natural source of stable cyclic peroxides, with selective antifungal or antibacterial activity. With the aim of identifying new bioactive molecules, we evaluated in vitro the antimalarial activity of the major cycloperoxides extracted from the sponge Plakortis simplex. The six-membered endoperoxide compounds plakortin and dihydroplakortin, but not the five-membered cycloperoxide plakortide E, inhibited the growth of cultured P. falciparum parasites, both chloroquine-sensitive D10 strain and chloroquine-resistant W2 strain. The IC50 values were similar for both compounds and in the range of 1263-1117 nM against D10, and 735-760 nM against W2, using the colorimetric parasite lactate dehydrogenase assay. The activity of plakortin and dihydroplakortin was significantly higher against chloroquine-resistant than chloroquine-susceptible parasites, following a pattern similar to that of artemisinin, although they were 50-fold less active. Moreover, plakortin and dihydroplakortin showed an additive effect when used in combination with chloroquine. These results support further studies on cycloperoxides of marine origin to characterize their mechanism of action and identify/synthesize new compounds with stronger antimalarial activity.

Diterpenoids from Cascarilla (Croton eluteria Bennet).

Cascarilla is a commercially available and cheap source of polyfunctionalized diterpenoids belonging to the clerodane structural type. In addition to the bitter triol cascarillin, 10 additional new diterpenoids (eluterins A-J) have been isolated and characterized by spectroscopic means. Structural diversity within cascarilla clerodanes involves mainly the linkage between the carbocyclic and the heterocyclic moieties and the functionalization of C-3, C-4, and C-6 of the decalin core. Cascarillin was shown to be a mixture of interconverting gamma-lactols and not a gamma-hydroxyaldehyde as previously reported.