Genotoxic activity of L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420.

L-asparaginase is an enzyme capable of hydrolyzing the substrate asparagine in aspartic acid and ammonia. Due to this mechanism of action observed, L-asparaginase is widely used in the treatment of Acute Lymphoblastic Leukemia, since these cells use asparagine for their survival. Because it is frequently used as an antineoplastic, it is necessary to evaluate its genotoxic effects. The aim of the present study was to evaluate cellular DNA damage after exposure to L-asparaginase produced by Streptomyces ansochromogenes UFPEDA 3420. NCIH-292, MCF-7 and MOLT-4 neoplastic cell lines and normal PBMC cells were used. L-Asparaginase used in this study was produced by actinobacteria S. ansochromogenes UFPEDA 3420, isolated and purified by chromatographic methods. L-Asparaginase induced micronucleus formation in PBMC cells and tumor lines when compared to the negative control. These data suggest that L-Asp appears to have a genotoxic effect very close to the positive control in normal cells (p < 0.05). The level of genomic damage measured by DNA breaks in alkaline SCGE assay was detected from the lowest concentration (12.5 µg/mL) to the highest concentration (50 µg/mL) for tumor cell lines and PBMC. In view of the above, new genotoxic studies will be carried out to better elucidate L-Asparaginase and its mutagenic potential, still unknown, enough for this drug to be safely used in conventional antineoplastic therapies.

Antifungal activity of the piroctone olamine in experimental intra-abdominal candidiasis.

This work aimed to evaluate the antifungal activity of piroctone olamine in the treatment of intra-abdominal candidiasis in an experimental model using Swiss mice. The mice (n = 6) were infected by intraperitoneal injection of 0.2 ml of C. albicans (10(7)cells/ml in saline). The animals were observed daily for clinical signs and mortality for 14 days. The treatment with piroctone olamine (0.5 mg/kg) was performed 72 h after infection by intraperitoneal administration. For comparison, a group of animals (n = 6) was treated with amphotericin B (0.5 mg/kg). The mycological diagnosis was made by collecting the liver, spleen and kidneys. Data regarding the fungal growth and mortality were analyzed statistically by Student's t test and analysis of variance (ANOVA), with level of significance set at P < 0.05. The difference in fungal growth scoring between the control group and the treatment groups (piroctone olamine and amphotericin B) was statistically significant (P < 0.05). The difference in fungal growth scoring between the treatment groups (piroctone olamine and amphotericin B) was not statistically significant (P < 0.05).

Differential genomic damage in different tumor lines induced by prodigiosin.

Prodigiosin is a secondary metabolite produced by Serratia marcercens. As this pigment is suggested to be a cancer drug, genotoxicity studies are necessary. The aim of the present investigation was to evaluate the genotoxic effects of prodigiosin on tumoral and normal cell lines, NCIH-292, MCF-7 and HL-60. A normal line BGMK was used as control. Genomic damage induced by prodigiosin was observed in all tumor lines as well as the control line. The pigment induced the formation of micronuclei in tumor cells. The present data confirm the antitumor potential of prodigiosin. However, these findings also raise concerns regarding its target-specific action, as genotoxic effects on normal cells also occurred.

Medicinal plants used as antitumor agents in Brazil: an ethnobotanical approach.

WE DESCRIBE THE MEDICINAL PLANTS THAT HAVE BEEN REPORTED TO BE ANTITUMOR AGENTS AND THAT HAVE BEEN USED IN ETHNOBOTANIC RESEARCH IN BRAZIL TO ANSWER THE FOLLOWING QUESTIONS: what is the abundance of plants reported to be antitumor in Brazil? Have the plant species used for tumor treatment in traditional Brazilian medicine been sufficiently examined scientifically? Our analysis included papers published between 1980 and 2008. A total of 84 medicinal plant species were reported to be used for cancer and tumor prevention or treatment; 69.05% of these were cited as being used for the treatment of tumors and cancer in general and 30.95% for specific tumors or cancers. The plants that were cited at a higher frequency were Aloe vera, Euphorbia tirucalli, and Tabebuia impetiginosa. At least, one pharmacological study was found for 35.71% of the species. Majority of the studies selected were conducted in rural communities and urban areas and in areas with traditional healers in Brazil. We found the following molecules to be the most studied in vitro and in vivo: silibinin, ß-lapachone, plumbagin and capsaicin. The species addressed here constitute interesting objects for future studies to various professionals in the field of natural products.

Indigofera suffruticosa: an alternative anticancer therapy.

Indigofera suffruticosa Mill (Fabeceae) occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell) cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53%) and maceration (62.62%) against sarcoma 180 in mice at a dose of 50 mg kg(-1) (intraperitoneally), based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

Synthesis and antiinflammatory activity of 4-amino-2-aryl-5-cyano-6-{3- and 4-(N-phthalimidophenyl)} pyrimidines.

Six new 4-amino-5-cyano-2,6-diarylpyrimidines 5a-h has been synthesized in a facile manner by reacting the appropriate arylamidines 4a-d with bisnitriles 3a-e. Reduction of the nitro group of 5a-e using Pd in ethyl acetate furnished 6a-e in good yields. Reaction of 6a-e individually with phthalic anhydride yielded 7a-e in good to excellent yields. The newly synthesized heterocycles were characterized by IR, (1)H-NMR and mass spectral data. Compounds 5f-h and 7a-e were also evaluated against inflammation. Pyrimidines 5g, h exhibited better antiinflammatory activity when compared with acetylsalicylic acid (ASA). Phthalimide derivatives 7a-e also presented antiinflammatory activity, and three of them, viz., 7a-c have been found to be twice more active than aspirin. Cytotoxical evaluations of compounds 7a-e using neoplastic cells (NCI-H(292) and Hep-2) presented 41% of growth inhibition of neoplastic cells NCI-H(292).