FLORA MARTINEZ FIGUEIRA MOREIRA
@ufgd.edu.br
School of Health Sciences
Federal University of Grande Dourados
Scopus Publications
Scopus Publications
Renu Verma, Flora Martinez Figueira Moreira, Agne Oliveira do Prado Morais, Katharine S. Walter, Paulo César Pereira dos Santos, Eugene Kim, Thiego Ramon Soares, Rafaele Carla Pivetta de Araujo, Bruna Oliveira da Silva, Andrea da Silva Santos,et al.
Elsevier BV
Katharine S. Walter, Paulo César Pereira dos Santos, Thais Oliveira Gonçalves, Bruna Oliveira da Silva, Andrea da Silva Santos, Alessandra de Cássia Leite, Alessandra Moura da Silva, Flora Martinez Figueira Moreira, Roberto Dias de Oliveira, Everton Ferreira Lemos,et al.
Elsevier BV
Renu Verma, Sunita Patil, Nan Zhang, Flora M. F. Moreira, Marize T. Vitorio, Andrea da S. Santos, Ellen Wallace, Devasena Gnanashanmugam, David H. Persing, Rada M. Savic,et al.
American Thoracic Society
RATIONALE
Standardized dosing of anti-tubercular drugs contributes to a substantial incidence of toxicities, inadequate treatment response, and relapse, in part due to variable drug levels achieved. Single nucleotide polymorphisms (SNPs) in the N-acetyltransferase-2 (NAT2) gene explain the majority of interindividual pharmacokinetic variability of isoniazid (INH). However, an obstacle to implementing pharmacogenomic-guided dosing is the lack of a point-of-care assay.
OBJECTIVES
To develop and test a NAT2 classification algorithm, validate its performance in predicting isoniazid clearance, and develop a prototype pharmacogenomic assay.
METHODS
We trained random forest models to predict NAT2 acetylation genotype from unphased SNP data using a global collection of 8,561 phased genomes. We enrolled 48 pulmonary TB patients, performed sparse pharmacokinetic sampling, and tested the acetylator prediction algorithm accuracy against estimated INH clearance. We then developed a cartridge-based multiplex qPCR assay on the GeneXpert platform and assessed its analytical sensitivity on whole blood samples from healthy individuals.
MEASUREMENTS AND MAIN RESULTS
With a 5-SNP model trained on two-thirds of the data (n=5,738), out-of-sample acetylation genotype prediction accuracy on the remaining third (n=2,823) was 100%. Among the 48 TB patients, predicted acetylator types were: 27 (56.2%) slow, 16 (33.3%) intermediate and 5 (10.4%) rapid. INH clearance rates were lowest in predicted slow acetylators (median 14.5 L/hr), moderate in intermediate acetylators (median 40.3 L/hr) and highest in fast acetylators (median 53.0 L/hr). The cartridge-based assay accurately detected all allele patterns directly from 25 ul of whole blood.
CONCLUSIONS
An automated pharmacogenomic assay on a platform widely used globally for tuberculosis diagnosis could enable personalized dosing of isoniazid.
Flora Martinez Figueira Moreira, Joyce Alencar Santos Radai, Vanessa Vilamaior de Souza, Claudia Rodrigues Berno, Flavio Henrique Souza de Araújo, Magaiver Andrade-Silva, Rodrigo Juliano Oliveira, Arielle Cristina Arena, Maria das Graças Müller de Oliveira Henriques, Candida Aparecida Leite Kassuya,et al.
Elsevier BV
Flora Martinez Figueira Moreira, Renu Verma, Paulo Cesar Pereira dos Santos, Alessandra Leite, Andrea da Silva Santos, Rafaele Carla Pivetta de Araujo, Bruna Oliveira da Silva, Júlio Henrique Ferreira de Sá Queiroz, David H. Persing, Erik Södersten,et al.
Elsevier BV
Katharine S. Walter, Mariana Bento Tatara, Kesia Esther da Silva, Flora Martinez Figueira Moreira, Paulo Cesar Pereira dos Santos, Dândrea Driely de Melo Ferrari, Eunice Atsuko Cunha, Jason R. Andrews, and Julio Croda
Centers for Disease Control and Prevention (CDC)
International migrants are at heightened risk for tuberculosis (TB) disease. Intensified incarceration at international borders may compound population-wide TB risk. However, few studies have investigated the contributions of migration, local transmission, or prisons in driving incident TB at international borders. We conducted prospective population-based genomic surveillance in 3 cities along Brazil’s central western border from 2014–2017. Although most isolates (89/132; 67%) fell within genomic transmission clusters, genetically unique isolates disproportionately occurred among participants with recent international travel (17/42; 40.5%), suggesting that both local transmission and migration contribute to incident TB. Isolates from 40 participants with and 76 without an incarceration history clustered together throughout a maximum-likelihood phylogeny, indicating the close interrelatedness of prison and community epidemics. Our findings highlight the need for ongoing surveillance to control continued introductions of TB and reduce the disproportionate burden of TB in prisons at Brazil’s international borders.
Jefferson Oliveira, Cristiane Shiguemoto, Amarith das Neves, Flora Moreira, Giovana Gomes, Renata Perdomo, Sandro Barbosa, Palimécio Guerrero Jr., Júlio Croda, and Adriano Baroni
Sociedade Brasileira de Quimica (SBQ)
In this work, it is described the design of twenty-four heterocyclic amine-azachalcones compounds through molecular hybridization of chalcone scaffold and fragments of isoniazid, fluoroquinolones, and linezolid with antituberculosis potential. The new compounds were synthesized via Claisen-Schmidt condensation, providing yields of 36-95%. Fifteen compounds showed antituberculosis activity against Mycobacterium tuberculosis H37Rv strain. Two amine-azachalcones 15 and 17 showed relevant biological activity with minimum inhibitory concentration (MIC) values of 6.62 and 4.85 μM, respectively. Compound 12 showed the best profile of antitubercular activity with MIC = 9.54 μM and selectivity index (SI) = 9.33. It was found that morpholine group is important to increase potency of antimycobacterial activity but also to add some toxicity to the chalcone molecular framework. The results described herein would be a guide in the designing of novel and optimized antitubercular derivatives based on the chalcone scaffold.
Hayley C. Warsinske, Aditya M. Rao, Flora M. F. Moreira, Paulo Cesar P. Santos, Andrew B. Liu, Madeleine Scott, Stephaus T. Malherbe, Katharina Ronacher, Gerhard Walzl, Jill Winter,et al.
American Medical Association (AMA)
Key Points Question How does a previously described blood-based 3-gene tuberculosis score perform as a screening test and a disease monitoring tool for all stages of tuberculosis? Findings In this nested case-contral study, the 3-gene tuberculosis score was associated with progression from latent Mycobacterium tuberculosis infection to active tuberculosis 6 months prior to sputum conversion with 86% sensitivity and 84% specificity, diagnosed patients with active tuberculosis with 90% sensitivity and 70% specificity, and correlated with treatment response and the severity of lung pathology. Meaning The 3-gene tuberculosis score can be implemented as a rapid, blood-based screening and triage test with the required World Health Organization target product profiles for the accurate detection and tracking of progressive, active, and treated tuberculosis disease.
Kamilla Felipe do Nascimento, Flora Martinez Figueira Moreira, Joyce Alencar Santos, Candida Aparecida Leite Kassuya, Julio Henrique Rosa Croda, Claudia Andrea Lima Cardoso, Maria do Carmo Vieira, Ana Lúcia Tasca Góis Ruiz, Mary Ann Foglio, João Ernesto de Carvalho,et al.
Elsevier BV
ETHNOPHARMACOLOGICAL RELEVANCE
Leaves from Psidium guineense Sw. are used in popular medicine for the treatment of inflammatory disease. However, there is no scientific evidence demonstrating this activity.
AIM OF THE STUDY
To evaluate the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of P. guineense and spathulenol (a major constituent). The study was conducted in part to provide evidence supporting the ethnobotanical use of the leaves of this species.
MATERIAL AND METHODS
The essential oil (EOPG) was extracted from the leaves of P. guineense by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). The major compound, spathulenol (PG-1), was isolated in a chromatographic column and characterized by nuclear magnetic resonance (NMR). EOPG and PG-1 were evaluated in vitro for antioxidant activity by DPPH, ABTS and MDA methods; anti-inflammatory potential was assessed using two models, including pleurisy and oedema, in mice. The impact of EOPG and PG-1 on cell proliferation was determined via spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay, and anti-Mycobacterium tuberculosis activity was determined using the REMA method.
RESULTS
A total of 38 components were identified from the EOPG, with the sesquiterpenic alcohol spathulenol (PG-1) (80.7%) being the major constituent. EOPG and PG-1 exhibited the highest antioxidant activities in the DPPH and MDA system compared with reference standard, with IC50 values ranging from 26.13 to 85.60μg/mL. Oral administration of EOPG and PG-1 showed significant inhibition in the Cg-induced mice paw oedema and pleurisy model. The EOPG (GI50 = 0.89μg/mL) and PG-1 (GI50 = 49.30μg/mL) were particularly effective against the ovarian cancer cell line. Both showed moderate antimycobacterial activity.
CONCLUSION
For the first time, this study demonstrated the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial properties of the essential oil of P. guineense (leaves were collected in Dourados-MS) and spathulenol, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect.
Raissa Borges Ishikawa, Maicon Matos Leitão, Roberto Mikio Kassuya, Luis Fernando Macorini, Flora Martinez Figueira Moreira, Claudia Andrea Lima Cardoso, Roberta Gomes Coelho, Arnildo Pott, Guilherme Martins Gelfuso, Julio Croda,et al.
Elsevier BV
ETHNOPHARMACOLOGICAL RELEVANCE
Doliocarpus dentatus is a medicinal plant widely used in Mato Grosso do Sul State for removing the swelling pain caused by the inflammation process and for treating urine retention.
AIM OF THE STUDY
The genotoxic aspects and the anti-inflammatory and antimycobacterial activity of the ethanolic extract obtained from the leaves of D. dentatus (EEDd) were investigated.
MATERIALS AND METHODS
The EEDd was evaluated against Mycobacterium tuberculosis, and the compound composition was evaluated and identified by nuclear magnetic resonance (NMR). The mice received oral administration of EEDd (30-300mg/kg) in carrageenan models of inflammation, and EEDd (10-1000mg/kg) was assayed by the comet, micronucleus, and phagocytosis tests and by the peripheral leukocyte count.
RESULTS
Phenols (204.04mg/g), flavonoids (89.17mg/g), and tannins (12.05mg/g) as well as sitosterol-3-O-β-D-glucopyranoside, kaempferol 3-O-α-L-rhamnopyranoside, betulinic acid and betulin were present in the EEDd. The value of minimal inhibitory concentration (MIC) of EEDd was 62.5µg/mL. The EEDd induced a significant decrease in the edema, mechanical hypersensitivity and leukocyte migration induced by carrageenan. The comet and micronucleus tests indicated that the EEDd was not genotoxic. The EEDd also did not change the phagocytic activity or the leukocyte perLipheral count.
CONCLUSIONS
The EEDd does not display genotoxicity, phagocytosis and could act as an antimycobacterial and anti-inflammatory agent. This study should contribute to ensuring the safe use of EEDd.
Lucas Noboru Fatori Trevizan, Kamilla Felipe do Nascimento, Joyce Alencar Santos, Candida Aparecida Leite Kassuya, Claudia Andrea Lima Cardoso, Maria do Carmo Vieira, Flora Martinez Figueira Moreira, Julio Croda, and Anelise Samara Nazari Formagio
Elsevier BV
ETHNOPHARMACOLOGICAL RELEVANCE
The leaves of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk. (Sapindaceae) are traditionally used as a natural anti-inflammatory agent; however, there are no scientific studies demonstrating its activity essential oil. The content of essential oil in A. edulis may be the chemical basis to explain its ethnobotanical uses, since infusions of this plant are used to treat inflammation in the traditional medicine in Brazil.
AIM OF THE STUDY
This study evaluated the anti-inflammatory, antioxidant and anti-mycobacterial activities of the essential oil (EOAE) and viridiflorol, its main compound.
MATERIAL AND METHODS
Essential oil from fresh leaves of A. edulis (EOAE) was obtained by hydrodistillation in a Clevenger-type apparatus. Forty-one compounds, accounting for 99.10% of the oil, were identified by gas chromatography-mass spectrometry (GC-MS). The major constituent of the oil was viridiflorol (30.88%). Additionally, the essential oil and viridiflorol were evaluated using an in vitro test against Mycobacterium tuberculosis and in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Both EOAE (30 and 100mg/kg) and viridiflorol (3 and 30mg/kg) by oral administration were assayed in carrageenan-induced mice paw oedema and pleurisy using subcutaneous injection of dexamethasone (0.5mg/kg) as the positive control.
RESULTS
EOAE and viridiflorol displayed moderate in vitro activity in the M. tuberculosis assay. In all tests, EOAE and viridiflorol showed moderate antioxidant activity compared with reference standards. Both EOAE and viridiflorol showed significant inhibition in the carrageenan-induced mice paw oedema via oral administration of the oil (30 and 100mg/kg), compound (3 and 30mg/kg), and subcutaneous injection of dexamethasone (0.5mg/kg, reference drug). Also EOAE and viridiflorol significantly inhibited carrageenan (Cg) induced pleurisy, reducing the migration of total leucocytes in mice by 62±5% (30mg/kg of oil), 35±8% (100mg/kg of oil), 71±5% (3mg/kg of viridiflorol) and 57±3% (30mg/kg of viridiflorol).
CONCLUSION
For the first time, the results from this work corroborate the literature, showing that A. edulis can be used as a natural anti-inflammatory agent. Moreover, both EOAE and viridiflorol exhibited biological activities, such as anti-mycobacterial, anti-inflammatory and antioxidant activity.
Flora M. F. Moreira, Julio Croda, Maria H. Sarragiotto, Mary A. Foglio, Ana L. T. G. Ruiz, João E. Carvalho, and Anelise S. N. Formagio
Sociedade Brasileira de Quimica (SBQ)
A series of β-carboline derivatives with amino or guanidinium were synthesized and evaluated in vitro against anti-Mycobacterium tuberculosis and for antiproliferative activities against nine human cancer cell lines. The compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline (24.9 µg mL-1) and 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline (26.9 µg mL-1) were the most active against M. Tuberculosis (MTB). Compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline and 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline, which had the same substituted groups, inhibited the growth of all human tumor cell lines with growth inhibitory activity (GI50) values from 1.37 to 9.20 mmol L-1. Also in this series, compounds 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline demonstrated significant activity against NCI/ADR cells. Among compounds with a terminal guanidine group, compounds 1-(4-hydroxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (27.8 µg mL-1) and 1-(3-nitrophenyl)-3-carboxamide(ethyl)guanidine β-carboline (37.4 µg mL-1) demonstrated the greatest activity against MTB. Additionally, compounds 1-(4-methoxyphenyl)-3-carboxamide(ethyl)guanidine β-carboline (GI50 = 0.45 mmol L-1) effectively inhibited growth and was highly selective against NCI/ADR. The in silico study revealed that 1-(4-hydroxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(ethylamine) β-carboline, 1-(4-hydroxyphenyl)-3-carboxamide(propylamine) β-carboline, 1-(4-methoxyphenyl)-3-carboxamide(propylamine) β-carboline and 1-(3-nitrophenyl)-3-carboxamide(propylamine) β-carboline compounds follow the rules established by Lipinski, suggesting that this compound has no problems with oral bioavailability.