Celso A. Camara

On the search for potential anti-Trypanosoma cruzi drugs: Synthesis and biological evaluation of 2-hydroxy-3-methylamino and 1,2,3-triazolic naphthoquinoidal compounds obtained by click chemistry reactions

Five 2-hydroxy-3-substituted-aminomethyl naphthoquinones, nine 1,2,3-triazolic para-naphthoquinones, five nor-β-lapachone-based 1,2,3-triazoles, and several other naphthoquinonoid compounds were synthesized and evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease, continuing our screening program for new trypanocidal compounds. Among all the substances, 16-18, 23, 25-29 and 30-33 were herein described for the first time and fifteen substances were identified as more potent than the standard drug benznidazole, with IC(50)/24h values in the range of 10.9-101.5 μM. Compounds 14 and 19 with Selectivity Index of 18.9 and 6.1 are important structures for further studies.

The encapsulation of β-lapachone in 2-hydroxypropyl-β-cyclodextrin inclusion complex into liposomes: a physicochemical evaluation and molecular modeling approach.

The aim of this study was to encapsulate lapachone (β-lap) or inclusion complex (β-lap:HPβ-CD) in liposomes and to evaluate their physicochemical characteristics. In addition, the investigation of the main aspects of the interaction between β-lap and 2-hydroxypropyl-β-cyclodextrin (HPβ-CD), using both experimental and molecular modeling approaches was discussed. Furthermore, the in vitro drug release kinetics was evaluated. First, a phase solubility study of β-lap in HPβ-CD was performed and the β-lap:HPβ-CD was prepared by the freeze-drying technique. A 302-fold increase of solubility was achieved for β-lap in HPβ-CD solution with a constant of association K(1:1) of 961 M(-1) and a complexation efficiency of β-lap of 0.1538. (1)H NMR, TG, DSC, IR, Raman and SEM indicated a change in the molecular environment of β-lap in the inclusion complex. Molecular modeling confirms these results suggesting that β-lap was included in the cavity of HPβ-CD, with an intermolecular interaction energy of -23.67 kJ mol(-1). β-lap:HPβ-CD and β-lap-loaded liposomes presented encapsulation efficiencies of 93% and 97%, respectively. The kinetic rate constants of 183.95±1.82 μg/h and 216.25±2.34 μg/h were calculated for β-lap and β-lap:HPβ-CD-loaded liposomes, respectively. In conclusion, molecular modeling elucidates the formation of the inclusion complex, stabilized through hydrogen bonds, and the encapsulation of β-lap and β-lap:HPβ-CD into liposomes could provide an alternative means leading eventually to its use in cancer research.

1,2,3-triazole-, arylamino- and thio-substituted 1,4-naphthoquinones: potent antitumor activity, electrochemical aspects, and bioisosteric replacement of C-ring-modified lapachones.

1,2,3-Triazole-, arylamino- and thio-substituted naphthoquinones (24, 8, and 2 representatives, respectively) were synthesized in moderate yields and evaluated against several human cancer cell lines (blood, ovarian, breast, central nervous system, colon, and prostate cancers and melanoma), showing, for some of them, IC50 values below 2 μM. The cytotoxic potential of the tested naphthoquinones was also assayed on non-tumor cells such as human peripheral blood mononucluear cells (PBMC) and two murine fibroblast lines (L929 and V79 cells). α-Lapachone- and nor-α-lapachone-based 1,2,3-triazoles and arylamino-substituted naphthoquinones showed potent cytotoxicity against different cancer cell lines. The compounds may represent promising new lead derivatives for anticancer drug development. The electrochemical properties of selected compounds were evaluated in an attempt to correlate them with antitumor activity.

Atividade antimicrobiana "in vitro" e determinação da concentração inibitória mínina (CIM) de fitoconstituintes e produtos sintéticos sobre bactérias e fungos leveduriformes

Regarding the problem of microbial resistance, the researches point to the use of new antibiotic which can be active against the emergent pathogens. This work aims to test the activity against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli e Pseudomonas aeruginosa) and leveduriform fungi (Candida albicans), and also the Minimum Inhibitory Concentration (MIC) of the constituent of Ocotea duckei Vattimo, lapachol and its synthetic derivatives a-lapachone, b-nor-lapachone, b-lapachone, a-nor-lapachone, b-3-iodin-lapachone and a-3-iodin-lapachone, as well as seven nitrogenated derivatives of lapachol obtained through semi synthesis. The achieved results stimulate the deepening of the studies for some of theses substances such as lapachol and its analogous which demonstrated antimicrobial activity. The substances which were active against S. aureus, were lapachol and the ethanolic extract of Ocotea duckei Vattimo, against Escherichia coli iangambin and against C. albicans the imides. The other substances did not show any activity against the tested bacteria.

Palynological Origin, Phenolic Content, and Antioxidant Properties of Honeybee-Collected Pollen from Bahia, Brazil

The aim of this study was to determine the palynological origin, phenolic and flavonoid content, and antioxidant properties of twenty-five samples of bee pollen harvested during a nine-month period (February–November) from the Canavieiras municipality (northeastern Brazil). Of the 25 samples analyzed, only two (February 01 and 02) were heterofloral. The predominant pollens in the samples analyzed during that month were: Cecropia, Eucalyptus, Elaeis, Mimosa pudica, Eupatorium, and Scoparia. Ethyl acetate fractions were analyzed by HPLC-DAD. The flavonoids isoquercetin, myricetin, tricetin, quercetin, luteolin, selagin, kaempferol, and isorhamnetin were detected. The flavonoid present in all 22 samples was isolated and identified as isorhamnetin 3-O-β-neohesperidoside. The total phenolic contents determined using the Folin-Ciocalteu reagent ranged from 41.5 to 213.2 mg GAE/g. Antioxidant activities based on the 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2-azinobis 3-ethylbenzothiozoline-6-sulfonic acid (ABTS), and Fe2+ ion chelating activity assays were observed for all extracts, and correlated with the total phenolic content.

Brine shrimp bioassay of some species of Solanum from Northestern Brazil

The methanolic extracts of 13 Specieis of the genus Solanum (Solanaceae) have been tested for bioactivity in Artemia salina. The extracts investigated were prepared from various parts (aerial parts, roots and fruits) of S. asperum, S. capsicoides, S. palinacantum, S. paludosum, S. paniculatum, S. paraibanum, S. sisymbriifolium, S. crinitum, S. diamantinense, S. megalonyx, S. torvum, S. asterophorum and S. stipulaceum. The lethal concentrations were determined for the extracts and among thirteen plants tested, four appear to be inactive. The extracts of the fruits of S. asperum (LC50 = 420.5 µg/mL) and S. paludosum (LC50 = 548.0 µg/mL), aerial parts of S. diamantinense (LC50 = 481.0 µg/mL) and S. sisymbrifolium (LC50 = 382.7 µg/mL), and the roots of S. asperum (LC50 = 593.4 µg/mL) and S. stipulaceum (LC50 = 823.1 µg/mL), all of which previously showed molluscicidal activity against Biomphalaria glabrata were also found to be active in the present study with brine shrimp.

Molluscicidal activity of 2-hydroxy-[1,4]naphthoquinone and derivatives

The toxic profile of lawsone (2-hydroxy-[1,4]naphthoquinone) and a series of [1,4]naphthoquinone derivatives was evaluated against the brine shrimp Artemia salina and against the mollusk Biomphalaria glabrata, the main transmitting vector of schistosomiasis in Brazil. Of the seventeen compounds tested nine fell below the threshold of 100 microg/mL set for potential molluscicidal activity by the World Health Organization. As a general rule derivatives with non-polar substituents presented the highest molluscicidal activities. These substances showed significant toxicity in A. salina lethality bioassay.

Synthesis of novel naphthoquinone-spermidine conjugates and their effects on DNA-topoisomerases I and II-alpha

Novos derivados do lapachol 2, nor-lapachol 3 e da lausona 4 foram sintetizados atraves do deslocamento nucleofilico das metoxinaftoquinonas 2a, 3a e 4a pela poliamina (PA) N1-Boc-N5-Bn-espermidina 1a. Os produtos, 2b, 3b e 4b, respectivamente, foram obtidos em bons rendimentos e caracterizados por metodos espectroscopicos e analiticos. Os ensaios preliminares de inibicao das enzimas topoisomerases (topo) I e II-a mostraram-se promissores: todos os compostos (1a 2b, 3b e 4b) inibiram a atividade catalitica da enzima topo II-a na dose de 2 µM. Considerando que somente a PA 1a nao inibiu a atividade da enzima na dose de 0,2 µM, as naftoquinonas apresentam-se como fragmentos em potencial para melhorar a atividade de PAs. Nenhum dos compostos inibiu a topo I na dose de 200 µM.

Composition and Molluscicidal Properties of Essential Oils from Leaves of Xylopia langsdorffiana A. St. Hil. et Tul. (Annonaceae)

Abstract The volatile fraction of Xylopia langsdorffiana leaves was analyzed by GC and GC/M S and tested for molluscicidal activity. With this methodology 19 different components were identified in the oil. Among them, germacrene D (22.9%), trans-β-guaiene (22.6%), β-caryophyllene (15.7%), and α-pinene (7.3%) were found to be the major constituents. The oil showed significant molluscicidal activity against Biomphalaria glabrata, with an LC90 value of 5.6 μg/mL, which falls below the threshold of 100 μg/mL, set for potential molluscicidal activity by the World Health Organization.

Synthesis and anti-Trypanosoma cruzi activity of naphthoquinone-containing triazoles: electrochemical studies on the effects of the quinoidal moiety.

In our continued search for novel trypanocidal compounds, twenty-six derivatives of para- and ortho-naphthoquinones coupled to 1,2,3-triazoles were synthesized. These compounds were evaluated against the infective bloodstream form of Trypanosoma cruzi, the etiological agent of Chagas disease. Compounds 17-24, 28-30 and 36-38 are described herein for the first time. Three of these novel compounds (28-30) were found to be more potent than the standard drug benznidazole, with IC50/24h values between 6.8 and 80.8μM. Analysis of the toxicity to heart muscle cells led to LC50/24h of <125, 63.1 and 281.6μM for 28, 29 and 30, respectively. Displaying a selectivity index of 34.3, compound 30 will be further evaluated in vivo. The electrochemical properties of selected compounds were evaluated in an attempt to find correlations with trypanocidal activity, and it was observed that more electrophilic quinones were generally more potent.