Vanadium polypyridyl compounds as potential antiparasitic and antitumoral agents: new achievements.

In the search for new therapeutic tools against diseases produced by kinetoplastid parasites five vanadyl complexes, [V(IV)O(L-2H)(phen)], including 1,10-phenanthroline (phen) and tridentate salicylaldehyde semicarbazone derivatives as ligands have been synthesized and characterized in the solid state and in solution by using different techniques. EPR suggested a distorted octahedral geometry with the tridentate semicarbazone occupying three equatorial positions and phen coordinated in an equatorial/axial mode. The compounds were evaluated in vitro on epimastigotes of Trypanosoma cruzi, causative agent of Chagas disease, Leishmania panamensis and Leishmania chagasi and on tumor cells. The complexes showed higher in vitro anti-trypanosomal activities than the reference drug Nifurtimox (IC(50) values in the range 1.6-3.8 µM) and increased activities in respect to the free semicarbazone ligands. In vitro activity on promastigote and amastigote forms of Leishmania showed interesting results. The compounds [VO(L1-2H)(phen)] and [VO(L3-2H)(phen)], where L1 = 2-hydroxybenzaldehyde semicarbazone and L3 = 2-hydroxy-3-methoxybenzaldehyde semicarbazone, resulted active (IC(50) 2.74 and 2.75 µM, respectively, on promastigotes of L. panamensis; IC(50) 19.52 and 20.75 µM, respectively, on intracellular amastigotes of L. panamensis) and showed low toxicity on THP-1 mammalian cells (IC(50) 188.55 and 88.13 µM, respectively). In addition, the complexes showed cytotoxicity on human promyelocytic leukemia HL-60 cells with IC(50) values of the same order of magnitude as cisplatin. The interaction of the complexes with DNA was demonstrated by different techniques, suggesting that this biomolecule could be a potential target either in the parasites or in tumor cells.

Composition of three essential oils, and their mammalian cell toxicity and antimycobacterial activity against drug resistant-tuberculosis and nontuberculous mycobacteria strains.

Tuberculosis (TB) is the most ancient epidemic disease in the world and a serious opportunistic disease in HIV/AIDS patients. The increase in multidrug resistant Mycobacterium tuberculosis (MDR-TB, XDR-TB) demands the search for novel antimycobacterial drugs. Essential oils (EOs) have been widely used in medicine and some EOs and their major components have been shown to be active against M. tuberculosis. The aim of this work was to evaluate the antimycobacterial and cell toxicity activities of three EOs derived from Salvia aratocensis, Turnera diffusa and Lippia americana, aromatics plants collected in Colombia. The EOs were isolated by hydrodistillation and analyzed by GC/MS techniques. The EOs were tested against 15 Mycobacterium spp using a colorimetric macrodilution method and against mammalian Vero and THP-1 cells by MTT. The activity was expressed as minimal concentration in microg/mL that inhibits growth, and the concentration that is cytotoxic for 50 or 90% of the cells (CC50 and CC90). The major components were epi-alpha-cadinol (20.1%) and 1,10-di-epi-cubenol (14.2%) for Salvia aratocensis; drima-7,9(11)-diene (22.9%) and viridiflorene (6.6%) for Turnera diffusa; and germacrene D (15.4%) and trans-beta- caryophyllene (11.3%) for Lippia americana. The most active EO was obtained from S. aratocensis, with MIC values below 125 microg mL(-1) for M. tuberculosis Beijing genotype strains, and 200 to 500 microg mL(-1) for nontuberculous mycobacterial strains. The EOs were either partially or non toxic to Vero and THP-1 mammalian cells with CC50 values from 30 to > 100 microg mL(-1), and a CC90 > 100 microg mL(-1). The EOs obtained from the three aromatic Colombian plants are an important source of potential compounds against TB. Future studies using the major EO components are recommended.

Composición química y actividad anti-tripanosomal de aceites esenciales obtenidos de Tagetes (Fam. Asteraceae), recolectados en Colombia / Chemical composition and anti-tripanosomal activity of essential oils from Tagetes (Asteraceae Fam) grown in Colombia

Introducción: La quimioterapia actual para enfermedad de Chagas es precaria con solo dos opciones de tratamiento: nifurtimox y benznidazol. Las plantas representan una fuente inmensa de moléculas potencialmente activas contra agentes infecciosos. Objetivo: Determinar la composición química y evaluar la actividad de aceites esenciales de Tagetes, recolectados en Colombia, contra Trypanosoma cruzi y su célula de mamífero hospedera. Materiales y métodos: Los aceites esenciales se obtuvieron de plantas colectadas en diversas regiones de Colombia; se extrajeron por hidrodestilación asistida por la radiación de microondas y se caracterizaron por cromatografía de gases acoplada a espectrometría de masas. La actividad de siete (7) aceites esenciales se determinó en epimastigotes, amastigotes intracelulares de T. cruzi y en células Vero. Los resultados fueron expresando como la concentración que inhibe (CI50, CI90) o destruye (CC50, CC90) 50 ó 90 % de parásitos o células. Resultados: Los componentes mayoritarios de los aceites fueron estragol, dihidrotagetona y cis-tagetona con diferencias de composición entre las especies de Tagetes evaluadas. Todos los aceites esenciales fueron activos en epimastigotes de T. cruzi. El aceite de T. heterocarpha fue activo en amastigotes intracelulares (CI50:41.35 µg/mL). Los aceites de T. caracasana y T. heterocarpha fueron tóxicos para las células Vero. Conclusiones: Los aceites esenciales obtenidos de T. heterocarpha, T. caracasana y T. zipaquirensis mostraron capacidad para inhibir el crecimiento de T. cruzi. Estudios complementarios de sus componentes mayoritarios se realizan actualmente.

Introduction: The current chemotheraphy of Chagas diseases is poor, with only two treatment options: nifurtimox and benznidazole. The plants represent an immense source of potentially active molecules against infectious agents. Aim: To determine the chemical composition and biological activity of Colombian Tagetes essential oils against Trypanosoma cruzi and its mammalian host cell. Materials and methods: Plants were collected in various region of Colombia and essential oils were extracted by microwave-assisted hidrodistillation and characterized by gas chromatography coupled with mass spectrometry. The activities of seven (7) essentials oils were determinate in epimastigotes and amastigotes of T. cruzi and on Vero cells. The result were expressed as the concentration to inhibit (IC50 IC90) or destroy (CC50 CC9) 50 or 90 % of parasites or cells. Results: Estragole, dihidrotagetone and cis-tagetone were the main components of essential oils, with quantitative differences between the evaluated Tagetes species. All essential oils were active in epimastigotes of T. cruzi. T. heterocarpha essential oil was active in intracellular amastigotes (IC50:41.35 µg/mL). The oils from T. caracasana y T. heterocarpha were toxic to Vero cells. Conclusions: The essential oils obtained from T. heterocarpha, T. caracasana and T. zipaquirensis inhibit the growth of T. cruzi. Additional studies on the major components activities against parasites are now under study.

Synthesis and in vitro activity of new tetrahydronaphtho[1,2-b]azepine derivatives against Trypanosoma cruzi and Leishmania chagasi parasites.

Series of 2-exo-aryl-1,4-epoxy-2,3,4,5-tetrahydronaphtho[1,2-b]azepines 3a-k and cis-2-aryl-4-hydroxy-2,3,4,5-tetrahydronaphtho[1,2-b]azepines 4a-j were synthesized and evaluated against free and intracellular live forms of Trypanosoma cruzi and Leishmania chagasi parasites using in vitro assays. Cell toxicity was also analyzed on Vero and THP-1 mammalian cell lines. The compounds 3c, 3f, and 4d were the most active against both live forms of T. cruzi parasites with low mammalian cell toxicity. Some compounds were active on free live forms of L. chagasi parasites but none was active on intracellular amastigotes of L. chagasi infecting THP-1 macrophages.