Synthesis and biological evaluation of caracasine acid derivatives.

A series of caracasine acid (1) derivatives were synthesized and evaluated for their in vitro cytotoxicity on human cancer-derived cell lines MCF-7 and PC-3, as well as for other activities such as antibacterial, antileishmanial and antitrypanosomal activity. Compound 1 was more effective than any of its derivatives against tested human cancer cell lines. PC-3 cells were more sensitive than MCF-7 to all compounds, particularly the methyl ester (2), the amide (9) and the epoxide (10). The evaluation of antiparasitic activity revealed that ester derivatives (2-8) and the amide derivative (9) were the most effective antileishmanial and antitrypanosomal compounds, even though their effect on Trypanosoma cruzi was modest. Finally, compound 1 and the derivatives evidenced a broad spectrum of antibacterial activity, as assayed against Gram-positive and Gram-negative bacteria.

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.

Isolation and identification of Streptomyces spp. from Venezuelan soils: morphological and biochemical studies. I.

The genus Streptomyces is represented in nature by the largest number of species and varieties among the family Actinomycetaceae. They differ greatly in their morphology, physiology, and biochemical activities, producing the majority of known antibiotics. The morphological and biochemical characteristics of 71 Streptomyces spp. isolated from soil samples collected at different places of Venezuela, are presented. A comparative analysis using the statistical software Minitab shows that 67 of these isolates are presumably new strains, since they possess a very low percentage of similarity with other reported species. Only four isolates shared 100% identity with one, two or three reported Streptomyces spp.

Chemical screening: a simple approach to visualizing Streptomyces diversity for drug discovery and further research.

The morphological and biochemical characteristics of Streptomyces species tend to be very similar, and thus the elucidation of their diversity is both time- and money-consuming. Here we evaluated various streptomycetes isolates using a chemical screening approach in order to establish their secondary metabolite patterns, thereby avoiding the possible discounting of morphologically similar strains. Results demonstrated that each isolate presented a unique pattern of secondary metabolites independently of their morphological and biochemical characteristics. We also established the enormous diversity in metabolic products among our isolates, and thus many potentially new metabolites may be studied in further research. Our results indicate that chemical screening is a simple selection method for recognizing the specific fingerprint of each isolate, highlighting the particular metabolic characteristics of each with respect to the other studied strains.