Carlos L E O M A R Zani | Fundação Oswaldo Cruz (original) (raw)
Papers by Carlos L E O M A R Zani
Memorias Do Instituto Oswaldo Cruz, 2003
Memorias Do Instituto Oswaldo Cruz, 2006
International Immunopharmacology, 2003
World Journal of Microbiology & Biotechnology, 2006
The ethyl acetate extract from the culture of the fungus Agrocybe perfecta (Rick) Singer was sele... more The ethyl acetate extract from the culture of the fungus Agrocybe perfecta (Rick) Singer was selected for further study in a screening of Brazilian basidiomycetes for bioactivity. The extract showed significant activity against the recombinant enzyme trypanothione reductase (TryR) from Trypanosoma cruzi, lymphocyte proliferation in human peripheral mononuclear cells (PBMC) stimulated with phytohemaglutinin (PHA), and the human cancer cell lines UACC-62 (melanoma), MCF-7 (mammary), and TK-10 (kidney). The chromatographic fractionation of the extract was monitored by the above bioassays and showed that agrocybin was the active component. Agrocybin, a known polyacetylene amide, showed an IC50 of 2 μM in the TryR assay but killed only 60% of the trypomastigote form of T. cruzi in infected murine blood even at 680 μM. This weaker activity could be due to the low temperature used to mimic banked blood or as a consequence of its inactivation by blood, already reported in the literature. On the other hand, it inhibited the proliferation of PBMC by 50% at 3.4 μM and the growth of the cancer cell lines at concentrations between 9 and 24.5 μM. Measurements of DNA fragmentation using flow cytometry suggest that agrocybin promotes cell death via apoptosis.
![Research paper thumbnail of Antiplasmodial and anti-trypanosomal activity of synthetic naphtho[2,3- b]thiophen-4,9-quinones](https://attachments.academia-assets.com/47818008/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry, 1997
Experimental Cell Research, 2003
Journal of Natural Products, 1997
The crude extract of Trixis vauthieri (Asteraceae) was active against the trypomastigote forms of... more The crude extract of Trixis vauthieri (Asteraceae) was active against the trypomastigote forms of Trypanosoma cruzi, the protozoan that causes Chagas' disease. Bioassay-guided fractionation of this extract afforded the trypanocidal flavonoids 5,4'-dihydroxy-7-methoxyflavanone (1) and 5,4'-dihydroxy-3,6,7-trimethoxyflavone (2) besides the inactive flavonoids 3,5,4'-trihydroxy-7-methoxyflavanone (3) and 5,4'-dihydroxy-3,6,7,8-tetramethoxy flavone (4). The trypanocidal activity of 1 and 2 and the presence of compounds 2 and 4 in Trixis vauthieri are reported here for the first time.
Journal of The Brazilian Chemical Society, 1998
... Josealdo Tonholo a,b , Luciano R. Freitas a , Fabiane C. de Abreu a , Dayse C. Azevedo a , Ca... more ... Josealdo Tonholo a,b , Luciano R. Freitas a , Fabiane C. de Abreu a , Dayse C. Azevedo a , Carlos L. Zani c , Alaíde B. de Oliveira d , and Marília OF Goulart a*. ... Bras. Ciênc. 1982, 54, 107. [ Links ]. 22. Pinto, AV; Pinto, M. do CFR; Aguiar, MA; Capella, RS An. Acad. Bras. Ciênc. ...
World Journal of Microbiology & Biotechnology, 2005
The ethyl acetate extract from the fungus Oudemansiella canarii grown in malt extract medium was ... more The ethyl acetate extract from the fungus Oudemansiella canarii grown in malt extract medium was evaluated against (a) the recombinant enzyme trypanothione reductase from Trypanosoma cruzi, (b) lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs) stimulated with phytohaemaglutinin, (c) the human tumour cell lineages MCF-7, TK-10 and UACC-62, and (d) the phytopathogenic fungus Cladosporium sphaerospermum. At 10 μg/ml, the crude extract was inactive against PBMC but inhibited the growth of UACC-62 cells by 47% and the enzyme trypanothione reductase (TryR). It also presented strong inhibition in the bioautographic assay with C. sphaerospermum. Chromatographic fractionation guided by this assay allowed the isolation of oudemansin A (1), a known fungitoxic compound that showed a minimum inhibitory concentration (MIC) of 1.25 μg/spot in the bioautographic assay. As oudemansin A was not active in the other assays, other components in the extract may be responsible for the observed activities by the crude extract against the UACC-62 cells or the TryR enzyme.
Journal of Natural Products, 1999
Bioorganic & Medicinal Chemistry Letters, 1997
Fems Microbiology Letters, 2008
Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiologica... more Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiological agents of several diseases in tropical areas of the world, for which there is an urgent need for effective and affordable treatment. In this regard, we are screening the Brazilian biodiversity, especially its flora and mycota, for natural products that could serve as leads for drug development against these diseases. Trypanothione reductase (TR) is an enzyme involved in the protection of Trypanosoma and Leishmania species against oxidative stress, and is considered to be a validated drug target. The endophytic fungus Alternaria sp. (UFMGCB55) was isolated from the plant Trixis vauthieri DC (Asteraceae), known to contain trypanocidal compounds. The organic extract of the culture of Alternaria sp. was able to inhibit TR by 99%, when tested at 20 μg mL−1. Fractionation of the extract identified altenusin, a biphenyl derivative with an IC50 value of 4.3±0.3 μM in the TR assay. This compound is the first in its class to have shown TR inhibitory activity, opening new perspectives for the design of more effective derivatives that could serve as drug leads for new chemotherapeutic agents to treat trypanosomiasis and leishmaniasis.
European Journal of Immunology, 2001
Memorias Do Instituto Oswaldo Cruz, 2010
Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Lati... more Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.
Journal of Chemical Ecology, 2006
Compounds from the metasternal and Brindley's glands of the blood-sucking bug, Triatoma infestans... more Compounds from the metasternal and Brindley's glands of the blood-sucking bug, Triatoma infestans, were identified by solid phase microextraction (SPME) and gas chromatography-mass spectrometry. Volatile compounds released by adult bugs during copulation or after mechanical disturbance were also characterized. Six compounds were identified and found consistently in all samples from metasternal glands. The most abundant were 3-pentanone, 2-methylbutanol, 3-pentanol, and an unidentified compound. The metasternal gland blends did not differ qualitatively between sexes. Compounds found in Brindley's glands were short chain acids, alcohols, esters, and a ketone with no qualitative differences between sexes. Isobutyric acid was the main component of this blend, and two new confirmed compounds were described as products of these glands: 2-butanone and 2-methylbutyric acid. 3-Pentanone was collected from the headspace over 33% of the copulating pairs of T. infestans. Volatiles found in the headspace of disturbed T. infestans adults included short-chain fatty acids, alcohols, esters, and ketones, with no qualitative differences between sexes. Both types of glands apparently discharge their contents after disturbance. However, most of the volatiles released by bugs after disturbance came from Brindley's glands. The locomotor activity of fourth instars increased significantly after stimulation with the odors emitted by disturbed adults, as compared with larvae stimulated by the odor of undisturbed adults or by clean air. We also studied the directional behavioral response of fifth instars to the disturbance scent in a locomotion compensator. Larvae exposed to volatiles released by disturbed adults walked away from the direction of the odor. The results suggest that this blend or part of it functions as an alarm pheromone for T. infestans. We suggest that the metasternal glands of this species are involved both in the sexual and the alarm contexts, and that the Brindley's glands probably have both alarm and defensive roles.
Pharmaceutical Biology, 1995
Page 1. International Journal of Pharmacognosy 1995, VOI. 33, NO. 3, pp. 177-180 0925-161 8/95/33... more Page 1. International Journal of Pharmacognosy 1995, VOI. 33, NO. 3, pp. 177-180 0925-161 8/95/3303-0177$6.00 0 Swets & Zeitlinger MOLLUSCICIDAL SAPONINS FROM THE PERICARP OF SAPZNDUS SAPONARIA AntBnia ...
European Journal of Medicinal Chemistry, 2005
Memorias Do Instituto Oswaldo Cruz, 1997
Memorias Do Instituto Oswaldo Cruz, 2003
Memorias Do Instituto Oswaldo Cruz, 2006
International Immunopharmacology, 2003
World Journal of Microbiology & Biotechnology, 2006
The ethyl acetate extract from the culture of the fungus Agrocybe perfecta (Rick) Singer was sele... more The ethyl acetate extract from the culture of the fungus Agrocybe perfecta (Rick) Singer was selected for further study in a screening of Brazilian basidiomycetes for bioactivity. The extract showed significant activity against the recombinant enzyme trypanothione reductase (TryR) from Trypanosoma cruzi, lymphocyte proliferation in human peripheral mononuclear cells (PBMC) stimulated with phytohemaglutinin (PHA), and the human cancer cell lines UACC-62 (melanoma), MCF-7 (mammary), and TK-10 (kidney). The chromatographic fractionation of the extract was monitored by the above bioassays and showed that agrocybin was the active component. Agrocybin, a known polyacetylene amide, showed an IC50 of 2 μM in the TryR assay but killed only 60% of the trypomastigote form of T. cruzi in infected murine blood even at 680 μM. This weaker activity could be due to the low temperature used to mimic banked blood or as a consequence of its inactivation by blood, already reported in the literature. On the other hand, it inhibited the proliferation of PBMC by 50% at 3.4 μM and the growth of the cancer cell lines at concentrations between 9 and 24.5 μM. Measurements of DNA fragmentation using flow cytometry suggest that agrocybin promotes cell death via apoptosis.
Bioorganic & Medicinal Chemistry, 1997
Experimental Cell Research, 2003
Journal of Natural Products, 1997
The crude extract of Trixis vauthieri (Asteraceae) was active against the trypomastigote forms of... more The crude extract of Trixis vauthieri (Asteraceae) was active against the trypomastigote forms of Trypanosoma cruzi, the protozoan that causes Chagas' disease. Bioassay-guided fractionation of this extract afforded the trypanocidal flavonoids 5,4'-dihydroxy-7-methoxyflavanone (1) and 5,4'-dihydroxy-3,6,7-trimethoxyflavone (2) besides the inactive flavonoids 3,5,4'-trihydroxy-7-methoxyflavanone (3) and 5,4'-dihydroxy-3,6,7,8-tetramethoxy flavone (4). The trypanocidal activity of 1 and 2 and the presence of compounds 2 and 4 in Trixis vauthieri are reported here for the first time.
Journal of The Brazilian Chemical Society, 1998
... Josealdo Tonholo a,b , Luciano R. Freitas a , Fabiane C. de Abreu a , Dayse C. Azevedo a , Ca... more ... Josealdo Tonholo a,b , Luciano R. Freitas a , Fabiane C. de Abreu a , Dayse C. Azevedo a , Carlos L. Zani c , Alaíde B. de Oliveira d , and Marília OF Goulart a*. ... Bras. Ciênc. 1982, 54, 107. [ Links ]. 22. Pinto, AV; Pinto, M. do CFR; Aguiar, MA; Capella, RS An. Acad. Bras. Ciênc. ...
World Journal of Microbiology & Biotechnology, 2005
The ethyl acetate extract from the fungus Oudemansiella canarii grown in malt extract medium was ... more The ethyl acetate extract from the fungus Oudemansiella canarii grown in malt extract medium was evaluated against (a) the recombinant enzyme trypanothione reductase from Trypanosoma cruzi, (b) lymphocyte proliferation in human peripheral blood mononuclear cells (PBMCs) stimulated with phytohaemaglutinin, (c) the human tumour cell lineages MCF-7, TK-10 and UACC-62, and (d) the phytopathogenic fungus Cladosporium sphaerospermum. At 10 μg/ml, the crude extract was inactive against PBMC but inhibited the growth of UACC-62 cells by 47% and the enzyme trypanothione reductase (TryR). It also presented strong inhibition in the bioautographic assay with C. sphaerospermum. Chromatographic fractionation guided by this assay allowed the isolation of oudemansin A (1), a known fungitoxic compound that showed a minimum inhibitory concentration (MIC) of 1.25 μg/spot in the bioautographic assay. As oudemansin A was not active in the other assays, other components in the extract may be responsible for the observed activities by the crude extract against the UACC-62 cells or the TryR enzyme.
Journal of Natural Products, 1999
Bioorganic & Medicinal Chemistry Letters, 1997
Fems Microbiology Letters, 2008
Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiologica... more Parasitic protozoan species belonging to the genera Trypanosoma and Leishmania are the etiological agents of several diseases in tropical areas of the world, for which there is an urgent need for effective and affordable treatment. In this regard, we are screening the Brazilian biodiversity, especially its flora and mycota, for natural products that could serve as leads for drug development against these diseases. Trypanothione reductase (TR) is an enzyme involved in the protection of Trypanosoma and Leishmania species against oxidative stress, and is considered to be a validated drug target. The endophytic fungus Alternaria sp. (UFMGCB55) was isolated from the plant Trixis vauthieri DC (Asteraceae), known to contain trypanocidal compounds. The organic extract of the culture of Alternaria sp. was able to inhibit TR by 99%, when tested at 20 μg mL−1. Fractionation of the extract identified altenusin, a biphenyl derivative with an IC50 value of 4.3±0.3 μM in the TR assay. This compound is the first in its class to have shown TR inhibitory activity, opening new perspectives for the design of more effective derivatives that could serve as drug leads for new chemotherapeutic agents to treat trypanosomiasis and leishmaniasis.
European Journal of Immunology, 2001
Memorias Do Instituto Oswaldo Cruz, 2010
Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Lati... more Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.
Journal of Chemical Ecology, 2006
Compounds from the metasternal and Brindley's glands of the blood-sucking bug, Triatoma infestans... more Compounds from the metasternal and Brindley's glands of the blood-sucking bug, Triatoma infestans, were identified by solid phase microextraction (SPME) and gas chromatography-mass spectrometry. Volatile compounds released by adult bugs during copulation or after mechanical disturbance were also characterized. Six compounds were identified and found consistently in all samples from metasternal glands. The most abundant were 3-pentanone, 2-methylbutanol, 3-pentanol, and an unidentified compound. The metasternal gland blends did not differ qualitatively between sexes. Compounds found in Brindley's glands were short chain acids, alcohols, esters, and a ketone with no qualitative differences between sexes. Isobutyric acid was the main component of this blend, and two new confirmed compounds were described as products of these glands: 2-butanone and 2-methylbutyric acid. 3-Pentanone was collected from the headspace over 33% of the copulating pairs of T. infestans. Volatiles found in the headspace of disturbed T. infestans adults included short-chain fatty acids, alcohols, esters, and ketones, with no qualitative differences between sexes. Both types of glands apparently discharge their contents after disturbance. However, most of the volatiles released by bugs after disturbance came from Brindley's glands. The locomotor activity of fourth instars increased significantly after stimulation with the odors emitted by disturbed adults, as compared with larvae stimulated by the odor of undisturbed adults or by clean air. We also studied the directional behavioral response of fifth instars to the disturbance scent in a locomotion compensator. Larvae exposed to volatiles released by disturbed adults walked away from the direction of the odor. The results suggest that this blend or part of it functions as an alarm pheromone for T. infestans. We suggest that the metasternal glands of this species are involved both in the sexual and the alarm contexts, and that the Brindley's glands probably have both alarm and defensive roles.
Pharmaceutical Biology, 1995
Page 1. International Journal of Pharmacognosy 1995, VOI. 33, NO. 3, pp. 177-180 0925-161 8/95/33... more Page 1. International Journal of Pharmacognosy 1995, VOI. 33, NO. 3, pp. 177-180 0925-161 8/95/3303-0177$6.00 0 Swets & Zeitlinger MOLLUSCICIDAL SAPONINS FROM THE PERICARP OF SAPZNDUS SAPONARIA AntBnia ...
European Journal of Medicinal Chemistry, 2005
Memorias Do Instituto Oswaldo Cruz, 1997