In vitro evaluation of new terpenoid derivatives against Leishmania infantum and Leishmania braziliensis

The activity of five (1-5) abietane phenol derivatives against Leishmania infantum and Leishmania braziliensis was studied using promastigotes and axenic and intracellular amastigotes. Infectivity and cytotoxicity tests were performed with J774.2 macrophage cells using Glucantime as a reference drug. The mechanisms of action were analysed by performing metabolite excretion and transmission electron microscopy ultrastructural studies. Compounds 1-5 were more active and less toxic than Glucantime. The infection rates and mean number of parasites per cell observed in amastigote experiments showed that derivatives 2, 4 and 5 were the most effective against both L. infantum and L. braziliensis. The ultrastructural changes observed in the treated promastigote forms confirmed that the greatest cell damage was caused by the most active compound (4). Only compound 5 caused changes in the nature and amounts of catabolites excreted by the parasites, as measured by ¹H nuclear magnetic resonance spectroscopy. All of the assayed compounds were active against the two Leishmania species in vitro and were less toxic in mammalian cells than the reference drug.

The antimicrobial activity of lapachol and its thiosemicarbazone and semicarbazone derivatives

Lapachol was chemically modified to obtain its thiosemicarbazone and semicarbazone derivatives. These compounds were tested for antimicrobial activity against several bacteria and fungi by the broth microdilution method. The thiosemicarbazone and semicarbazone derivatives of lapachol exhibited antimicrobial activity against the bacteria Enterococcus faecalis and Staphylococcus aureus with minimal inhibitory concentrations (MICs) of 0.05 and 0.10 µmol/mL, respectively. The thiosemicarbazone and semicarbazone derivatives were also active against the pathogenic yeast Cryptococcus gattii (MICs of 0.10 and 0.20 µmol/mL, respectively). In addition, the lapachol thiosemicarbazone derivative was active against 11 clinical isolates of Paracoccidioides brasiliensis, with MICs ranging from 0.01-0.10 µmol/mL. The lapachol-derived thiosemicarbazone was not cytotoxic to normal cells at the concentrations that were active against fungi and bacteria. We synthesised, for the first time, thiosemicarbazone and semicarbazone derivatives of lapachol. The MICs for the lapachol-derived thiosemicarbazone against S. aureus, E. faecalis, C. gattii and several isolates of P. brasiliensis indicated that this compound has the potential to be developed into novel drugs to treat infections caused these microbes.

The efficacy of 2-nitrovinylfuran derivatives againstLeishmania in vitro and in vivo

Despite recent advances in the treatment of some forms of leishmaniasis, the available drugs are still far from ideal due to inefficacy, parasite resistance, toxicity and cost. The wide-spectrum antimicrobial activity of 2-nitrovinylfuran compounds has been described, as has their activity against Trichomonas vaginalis and other protozoa. Thus, the aim of this study was to test the antileishmanial activities of six 2-nitrovinylfurans in vitro and in a murine model of leishmaniasis. Minimum parasiticide concentration (MPC) and 50% inhibitory concentration (IC50) values for these compounds against the promastigotes of Leishmania amazonensis, Leishmania infantum and Leishmania braziliensis were determined, as were the efficacies of two selected compounds in an experimental model of cutaneous leishmaniasis (CL) caused by L. amazonensis in BALB/c mice. All of the compounds were active against the promastigotes of the three Leishmania species tested. IC50 and MPC values were in the ranges of 0.8-4.7 µM and 1.7-32 µM, respectively. The compounds 2-bromo-5-(2-bromo-2-nitrovinyl)-furan (furvina) and 2-bromo-5-(2-methyl-2-nitrovinyl)-furan (UC245) also reduced lesion growth in vivo at a magnitude comparable to or higher than that achieved by amphotericin B treatment. The results demonstrate the potential of this class of compounds as antileishmanial agents and support the clinical testing of Dermofural(r) (a furvina-containing antifungal ointment) for the treatment of CL.

Antifungal derivatives from Piper mollicomum and P. lhotzkyanum (Piperaceae)

Bioguided fractionation of the extracts from leaves of Piper mollicomum and Piper lhotzkyanum against the fungi Cladosporium cladosporioides and C. sphaerospermum afforded seven bioactive compounds, four being chromenes: methyl 2,2-dimethyl-2H-chromene-6-carboxylate, methyl 8-hydroxy-2,2-dimethyl-2H-chromene-6-carboxylate, 2-methyl-2-[4'-methyl-3'-pentenyl]-2H-1-benzopyran-6-carboxylic acid, 2,2-dimethyl-2H-chromene-6-carboxylic acid, one a dihydrochalcone: 2',6'-dihydroxy-4'-methoxydihydrochalcone, and two flavanones: 7-methoxy-5,4'-dihydroxy-flavanone and 7,4'-dimethoxy-5-hydroxy-flavanone. The structures of the bioactive isolated derivatives were elucidated by interpretation of their NMR data [¹H and 13C (BBD, DEPT 135º)], and mass spectral data as well as by comparison with data described in the literature.

An easy and direct method for the synthesis of 1,2,4-triazole derivatives through carboxylic acids and hydrazinophthalazine

We have developed an easy method for the synthesis of thirteen compounds derived from 1,2,4-triazoles through a carboxylic acid and hydrazinophthalazine reaction, with a 75-85% yield mediated by the use of agents such as 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide hydrochloride and 1-hydroxybenzotriazole. The operational simplicity of this method and the good yield of products make it valuable for the synthesis of new compounds with pharmacological activity.

Synthesis and antitubercular activity of isoniazid condensed with carbohydrate derivatives

A series of 13 compounds analogous of isoniazid condensed with carbohydrate was synthesized and evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv using Alamar Blue susceptibility test and the activity expressed as the minimum inhibitory concentration (MIC90) in μg/mL. Several compounds exhibited antitubercular activity (0.31-3.12 μg/mL) when compared with first line drugs such as isoniazid (INH) and rifampicin (RIP) and could be a good starting point to develop new compounds against tuberculosis.

Synthesis and biological activity of n-{5-(4-methylphenyl) diazenyl-4-phenyl-1, 3-thiazol-2-yl}benzamide derivatives

In the present study, various amides of 2-amino-5-(4-methylphenyl)-diazenyl-4-phenyl-1, 3-thiazole was synthesized and their biological activities were evaluated. All the synthesized compounds were characterized by the combination of elemental analysis and standard spectroscopic methods. They are screened for anti-bacterial activity against Escherichia coli and Staphylococcus aureus as well as screened for antifungal activity against Aspergillus niger and Apergillus oryzae by cup plate method at 1 µg/ mL concentration in DMF.

Efficient synthesis of sulfonamide derivatives on solid supports catalyzed using solvent-free and microwave-assisted methods

In this work we report the synthesis of sulfonamide derivatives using a conventional procedure and with solid supports, such as silica gel, florisil, alumina, 4Å molecular sieves, montmorillonite KSF, and montmorillonite K10 using solvent-free and microwave-assisted methods. Our results show that solid supports have a catalytic activity in the formation of sulfonamide derivatives. We found that florisil, montmorillonite KSF, and K10 could be used as inexpensive alternative catalysts that are easily separated from the reaction media. Additionally, solvent-free and microwave-assisted methods were more efficient in reducing reaction time and in increasing yield.

Synthesis of quinoxaline 1,4-di-N-oxide derivatives on solid support using room temperature and microwave-assisted solvent-free procedures

We describe the synthesis of 12 new ethyl and methyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives on solid supports with room temperature and microwave-assisted solvent-free procedures. Results show that solid supports have good catalytic activity in the formation of quinoxaline 1,4-di-N-oxide derivatives. We found that florisil and montmorillonite KSF and K10 could be used as new, easily available, inexpensive alternatives of catalysts. Additionally, room temperature and microwave-irradiation solvent-free synthesis was more efficient than a conventional procedure (Beirut reaction), reducing reaction time and increasing yield.

Synthesis, antimicrobial and cytotoxic activities of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-one and 2-[(pyridine-4-ylmethylene) hydrazono]-thiazolidin-4-one derivatives

A new series of 5-benzylidene-2-[(pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 4a-l have been synthesized. These compounds were designed by a molecular hybridization approach. 2-[(Pyridine-4-ylmethylene)hydrazono]-thiazolidin-4-ones 3a-d were also obtained and used as intermediates to give the target compounds. The in vitro antimicrobial and cytotoxic activities were evaluated for both series. The intermediate 3b showed considerable antibiotic activity against B. subtilis and C. albicans. In the cytotoxic activity compounds 3b (IC50= 4.25 ± 0.36 µg/mL) and 4l (IC50= 1.38 ± 0.04 µg/mL) were effective for inhibition of human erythromyeloblastoid leukemia (K-562) and human lung carcinoma (NCI-H292) cell lines, respectively.

Nitro derivatives and other constituents of Aristolochia melastoma

A phytochemical study of Aristolochia melastoma Manso has led to the isolation and identification of 20 known compounds, including aristolochic acids, sodium aristolochates, lignan, flavonoids, and nitro phenylethyl derivatives. Their structures were established by spectroscopic analysis. The presence of thalictricoside and secoisolariciresinol dimethyl ether diacetate is reported for the first time in the Aristolochiaceae family. In addition, the presence of nitro compounds in this species is significant.

Synthesis of 2-azetidinone derivatives of 6-nitro-1H-indazole and their biological importance

A new series of 3-chloro-1-{[2-(6-nitro-1H-indazol-1-yl)ethyl]amino}-4-(substituted phenyl)-2-azetidinones (4a-j) was synthesized in four steps from 6-nitro-1H-indazole and characterized by IR, ¹H NMR, 13C NMR, FAB-mass spectrometry and chemical methods. Compounds 4(a-j) were screened in vitro for their antibacterial, antifungal and antitubercular activities against some selected microorganism and for their antiinflammatory activity (in vivo) against albino rats (either sex). All above activities of compounds 4(a-j) showed acceptable results.

Phenolic derivatives and other chemical compounds from Cochlospermum regium

This study describes the chemical investigation of the ethyl acetate fraction obtained from the hydroethanolic extract of the xylopodium of Cochlospermum regium (Mart. & Schr.) Pilger, which has been associated with antimicrobial activity. Phytochemical investigation produced seven phenol derivatives: ellagic acid, gallic acid, dihydrokaempferol, dihydrokaempferol-3-O-β-glucopyranoside, dihydrokaempferol-3-O-β-(6"-galloyl)-glucopyranoside, pinoresinol, and excelsin. It also contained two triacylbenzenes, known as cochlospermines A and B. The hydroethanolic extract and its fractions exhibited antimicrobial activity (0.1 mg/mL) against Staphylococcus aureus and Pseudomonas aeruginosa. Gallic acid showed activity against S. aureus. Dihydrokaempferol-3-O-β-(6"-galloyl)-glucopyranoside is reported here for the first time in the literature.

DFT study on low molecular weight α,α-ditert-butyl-4H-cyclopenta[2,1-b,3;4-b']dithiophene and α,α-ditert-butyl-4H-cyclopenta[2,1-b,3;4-b']dithiophene S-oxide bridged derivatives

The equilibrium geometries of α,α-ditert-butyl-4H-cyclopenta[2,1-b,3;4-b']dithiophene (DBDT) and α,α-ditert-butyl-4H-cyclopenta[2,1-b,3;4-b']dithiophene S-oxide (DBDTO) were studied at the DFT level of theory with a standard 6-311G* basis set. The molecular structures of the DBDT series were more planar than the corresponding DBDTO series, as revealed by dihedral angles. The UV-visible absorption calculated at TD-DFT/6-311G* showed two absorption peaks for all the molecules except C=S and C=O bridged molecules. In DBDTOs, C=S and C=O bridged molecules showed three and four absorption peaks, respectively. The DBDTOs had lower band gaps and longer wavelengths compared to the corresponding DBDTs.

Synthesis, characterization, and biological activity of a new class of dialkylphosphorylhydrazone derivatives of isatin

Sixteen dialkylphosphorylhydrazones were synthesized by condensation of phosphorylhydrazines with substituted isatins. Products were characterized by FTIR, ¹H-NMR, 13C-NMR, and 31P-NMR. Fungicidal activities of these compounds against Rhizoctonia solani and Fusarium oxysporum were also evaluated. Some compounds inhibited the growth of Rhizoctonia solani and Fusarium oxysporum by 43% and 51%, respectively. These compounds exhibited no effects on germination of lettuce seeds (Lactuca sativa L).