Nieves Canudas

New Access to Sesquiterpene Hydroquinones: Synthesis of (+)‐ent‐Chromazonarol

Abstract A facile access to optically active (+)‐ent‐chromazonarol ent‐1, isolated from the sponge Disidea pallescens, is reported from commercially available (+)‐manool 4.

Synthesis and antimalarial activities of optically active labdane-type diterpenes

An efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). Compounds 5, 6, 7 and 9 were evaluated as inhibitors of the β-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. Compound 9 was the most promising compound, showing a positive correlation between in vitro and in vivo activities.

Facile and Simple Synthesis of Ring C Aromatic Diterpenes: Synthesis of (+)-13-Hydroxypodocarpa-8,11,13-triene and (+)-7-Deoxynimbidiol

Abstract A convenient synthesis of the natural (+)-13-hydroxypodocarpa-8,11,13-triene 1 and (+)-7-deoxynimbidiol 2 from (+)-manool 4 has been achieved in good overall yield.

Facile access to optically active ring C aromatic diterpenes from (+)-manool. Synthesis of (+)-13-hydroxypodocarpa-8,11,13-triene, (+)-7-deoxynimbidiol and (+)-nimbidiol

A practical method for the synthesis of naturally occurring ring C aromatic diterpenes from (+)-manool via key intermediate β-enone is described. The natural (+)-13-hydroxypodocarpa-8,11,13-triene, the antitumour (+)-7-deoxynimbidiol, and (+)-nimbidiol were prepared in good overall yields.

Synthesis and biological evaluation of ( − )-13,14-dihydroxy-8,11,13-podocarpatrien-7-one and derivatives from (+)-manool

13,14-Dihydroxy-8,11,13-podocarpatrien-7-one (1) and a series of ring C aromatic diterpene derivatives were synthesised from (+)-manool (4) and evaluated for their cytotoxic, leishmanicidal and trypanocidal activities. Our results indicated that compound 1 and other podocarpane-type intermediates are cytotoxic. Cleavage of C6–C7 bond of compound 7 improved cytotoxic activity, indicating that, in particular, the 6,7-seco-podocarpane-type compound 20 might serve as a lead compound for further development.

Photosensitizing properties of Actarit, an antirheumatic drug.

The photobiological properties of 4-acetylaminophenylacetic acid (Actarit, ACT, MS-932, CAS 18699-02-0) were studied using in vitro phototoxicity assays: photohemolysis, photoperoxidation of linoleic acid and Candida sp phototoxicity test. ACT reduced nitro blue tetrazolium (NBT) when irradiated with lambda > or = 300 nm in deoxygenated aqueous buffer solution (pH 7.4). The photohemolysis rate and photoperoxidation of linoleic acid were inhibited significantly by reduced glutathione. ACT was phototoxic to Candida sp. The isolation and identification of the photodegradation products of ACT in phosphate buffered saline solution (pH 7.4) and methanol were studied under aerobic conditions. Four compounds were identified and two of them isolated and characterized by spectroscopic methods. A photodecarboxylation with the participation of oxygen via a type I mechanism was proposed for the photodegradation of ACT which undergoes direct electron transfer from the excited state of ACT carboxylate and homolytic rupture of the alpha-carbon bond. A photodynamic mechanism involving radicals and electron transfer reactions was suggested for the observed in vitro phototoxicity.

Facile access to labdane-type diterpenes: synthesis of coronarin C, zerumin B, labda-8(17), 13(14)-dien-15,16-olide and derivatives from (+)-manool

A practical method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8, is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9 and coronarin C 1, compound 8 and zerumin B 6 via a furan photosensitised oxygenation reactions.

Antimalarial effect of two photo-excitable compounds in a murine model with Plasmodium berghei (Haemosporida: Plasmodiidae)

Malaria represents a major health problem worldwide, affecting around 198 million people in 2016 according to WHO database. For decades, anti-malarial drug therapy has been used in the battle against this disease and its uncontrolled usage in endemic areas has developed the appearance of the drug resistance. Thus, it has emerged the necessity of finding new treatments that could be used as an alternative cure to malaria infection. The aim of this work was the evaluation of two photo-excitable compounds: Compound 1, which is (2E)-3-(4-dimethylamino-phenyl)-1-(4-imidazol-1-yl-phenyl)prop-2-en-1-one) and Compound 2, (1E,4E)1-[4-(dimethylamino)phenyl]-5-(4-methoxyphenyl)-1,4-pentadiene-3-one) as possible anti-malaria drugs with Plasmodium berghei ANKA strain in BALB/c mice as murine model. Cytotoxicity effect was evaluated by a cell proliferation by colorimetry assay (MTS); and the drug incorporation into the parasite was assessed in vitro with Indirect Immunofluorescence Assay (IFA) to determine the localization of the drugs into the parasitized red blood cells (RBCs). Finally, the curative effect of compounds no-radiation (fundamental state) and ration drugs were evaluated by oral drug administration of this drugs in BALB/c mice and chloroquine was used as positive control. This curative effect was determined daily by the parasitemia percentage. The results showed that both compounds were cytotoxic in fundamental state. Furthermore, cytotoxic effect was increased after radiation into the Solar Simulator, and compound 2 was more cytotoxic than compound 1. Curative assays showed that both compounds in fundamental state were non effective as anti-malarial drug. However, in the curative assays in the mice treated with compound 2, when this was ration showed a survival rate of 33 % and a parasitemia percentage decrease in compare to compound 1. Although the compounds did not show a similar or better anti-malarial effect than Chloroquine, Compound 2 presented certain anti-malarial effect after solar radiation. Rev. Biol. Trop. 66(2): 880-891. Epub 2018 June 01.