A Comprehensive View on (-)-7-Oxo-ent-kaur-16-en-19-oic Acid, the Major Constituent of Xylopia sericea Leaves Extract: Complete NMR Assignments, X-Ray Crystallographic Structure, in Vitro Antimalarial Activity and Cytotoxicity.

Bioguided fractionation of Xylopia sericea antiplasmodial dichloromethane leaves extract led to the isolation of (-)-7-oxo-ent-kaur-16-en-19-oic acid (C20 H28 O3 ) that was identified by a combination of 1D and 2D NMR experiments (COSY, HMBC, HSQC, HSQC-TOCSY, HSQC-NOESY and NOESY) and by X-ray crystallography. A feature to be pointed out is its (4R) configuration that was inferred from the NOE experiments (HSQC-NOESY and NOESY) and X-ray crystallography. In vitro evaluation of this rare diterpene acid against the chloroquine-resistant strain Plasmodium falciparum W2 by the PfLDH method showed it disclosed a low antiplasmodial activity and was not cytotoxic to HepG2 cells (CC50 862.6±6.7 µm) by the MTT assay. The unequivocal NMR signals assignments, the X-ray crystallographic structure, the assessment to the bioactivities and the occurrence this diterpene in X. sericea are reported here for the first time.

Potential anti-herpes and cytotoxic action of novel semisynthetic digitoxigenin-derivatives.

In recent years, new therapeutic possibilities were proposed for cardiac glycosides traditionally used to treat heart diseases, such as anticancer and antiviral activities. In this sense, this work aimed to synthesize the readily accessible 3ß-azido-3-deoxydigitoxigenin (5) from digitoxigenin (1). Two new series of compounds were obtained from derivative (5): (i) O-glycosyl trizols through click chemistry with propargyl glycosides; and (ii) compounds substituted in the alpha carbonyl position with different residues linked via an amino-group. All obtained derivatives have their chemical structures confirmed, and their anti-herpes (against HSV-types 1 and 2 replication) and cytotoxic (against PC3, A549, HCT-8 and LNCaP cell lines) activities evaluated. Compounds 10 and 11 exhibited the most promising results against HSV-1 (KOS and 29-R strains) and HSV-2 (333 strain) replication with SI values > 1000. Both compounds were also the most cytotoxic for the human cancer cell lines tested with IC50 values similar to those of paclitaxel. They also presented reduced toxicity toward non-cancerous cell lines (MRC-5 and HGF cells). Promising compounds were tested in regard to their ability to inhibit Na+/K+-ATPase. The inhibition rate correlates suitably with the bioactivity demonstrated by those both compounds against the different human cancer cells tested as well as against HSV replication. Moreover, the results showed that specific chemical features of compound 10 and 11 influenced the bioactivities tested. In summary, it was possible to obtain novel digitoxigenin-derivatives with remarkable cytotoxic and anti-herpes activities as well as low toxicity and high selectivity. In this way, they could be considered potential molecules for the development of new drugs.

Diterpenes from Alomia myriadenia (Asteraceae) with cytotoxic and trypanocidal activity.

Further investigation of the aerial parts of Alomia myriadenia revealed an halimane diterpene identified as ent-8S,12S-epoxy-7R,16-dihydroxyhalima-5(10),13-dien-15,16-olide along with the known ent-16-hydroxylabda-7,13-dien-15,16-olide, ent-12R-hydroxylabda-7,13-dien-15,16-olide, 6,7-methylenedioxycoumarin (ayapin), and kaempferol-7-methylether (rhamnocitrin). Evaluated in a panel of human cancer cell lines, the 16-hydroxylabade diterpene was the most active, showing an ED(50) value of 0.3 mug/ml against Lu1 (human lung cancer) cells. Tested in vitro against Trypanosoma cruzi in infected murine blood, this compound caused lysis of 100% of the parasites at 250 mug/ml.