Maria do Carmo F. R. Pinto

Trypanocidal activity of isolated naphthoquinones from Tabebuia and some heterocyclic derivatives: a review from an interdisciplinary study

Naphthoquinones isolated from the wood of trees of the families Bignoniaceae and Verbenaceae have been subjected to an interdisciplinary study since the seventies, when Dr. Benjamin Gilbert, at the Federal University of Rio de Janeiro, launched a program on the chemistry of natural products active against endemic diseases. In this paper we describe the synthesis of five naphthoimidazoles, derived from this program and their activity towards T. cruzi, the etiologic agent of Chagas disease. We also review the influence of chemical structure on trypanocidal action of naphthoquinones and of derived heterocycles with imidazole, oxazole, phenoxazine, indole, dipyrane and cyclopentene rings. The overall analysis corroborates the tendency of trypanocidal activity in compounds with an imidazole or oxazole ring linked to a naphthopyrane structure. Two naphthoimidazoles presented higher activities (14.5x and 34.8x) than the standard crystal violet. Emphasis is given to the biodiversity of the Brazilian flora as a starting point for the development of an autonomous and creative medicinal chemistry.

Molluscicidal activity of 2-hydroxy-3-alkyl-1,4-naphthoquinones and derivatives.

In the search for new molluscicidal agents we tested the activity of lapachol and other 2-hydroxy-3-alkylnaphthoquinones possessing nitrogenated alkyl chains, against the snail Biomphalaria glabrata. Lapachol, isolapachol and nor-lapachol showed strong molluscicidal activity against the adult snail (LD(90)<10 ppm) and significant toxicity against snail egg masses (LD(90)<0.2 ppm). As lapachol is easily extracted, and the derivatives can be synthesised without any difficulty, large-scale synthesis and field tests can be conducted, with a view to large-scale molluscicidal programs.

3-Arylamino and 3-Alkoxy-nor-β-lapachone Derivatives: Synthesis and Cytotoxicity against Cancer Cell Lines

Several 3-arylamino and 3-alkoxy-nor-beta-lapachone derivatives were synthesized in moderate to high yields and found to be highly potent against cancer cells SF295 (central nervous system), HCT8 (colon), MDA-MB435 (melanoma), and HL60 (leukemia), with IC(50) below 2 microM. The arylamino para-nitro and the 2,4-dimethoxy substituted naphthoquinones showed the best cytoxicity profile, while the ortho-nitro and the 2,4-dimethoxy substituted ones were more selective than doxorubicin and similar to the precursor lapachones, thus emerging as promising new lead compounds in anticancer drug development.

A Novel Synthesis of α and β -Pyran-naphthoquin one Tetracyclic

Abstract The natural pyran-naphthoquinone (I,II) has been reported as an agent against Trypanosoma Cruzi and some kinds of tumors1,2,3. We hav recently reported a new synthesis of substituted pyran-naphthoquinone (III) by alkylation of 2-hyoxy-1,4-naphthoquinone with some natural mono-erpenes (citral, farnesal and phytal) followed by hydrogenation3.

Naphthoquinone-based chalcone hybrids and derivatives: synthesis and potent activity against cancer cell lines

Novel naphthoquinone-based chalcones were prepared from the reaction between 3-bromo-nor-β-lapachone and amino-chalcones. Lapachone derivatives are also described here. All the substances were evaluated against cancer and normal cell lines and several compounds demonstrated potent antitumor activity.

1,3-Azoles from ortho-naphthoquinones: synthesis of aryl substituted imidazoles and oxazoles and their potent activity against Mycobacterium tuberculosis.

Twenty-three naphthoimidazoles and six naphthoxazoles were synthesised and evaluated against susceptible and rifampicin- and isoniazid-resistant strains of Mycobacterium tuberculosis. Among all the compounds evaluated, fourteen presented MIC values in the range of 0.78 to 6.25 μg/mL against susceptible and resistant strains of M. tuberculosis. Five structures were solved by X-ray crystallographic analysis. These substances are promising antimycobacterial prototypes.

A macrolactone from benzo[a]phenazine with potent activity against Mycobacterium tuberculosis

We report here an alternative to the MCPBA or ozonolysis-based oxidation methods of quinoxaline-featuring compounds prepared from beta-lapachones. The use of peracetic acid allowed a simple preparation of the corresponding macrolactones by cleavage of the ring system. These lactones were evaluated for their antimycobacterial potential and compound 4 turned out to have an MIC of 0.62 microg per mL on Mycocabteriumtuberculosis H37Rv. These results justify further research into its value as a potential lead for an original treatment of tuberculosis.

Fluorescent symmetric phenazines from naphthoquinones: 3. Steady-state spectroscopy and solvent effect of seven phenazine derivatives: structure–photophysics correlations

Abstract The fluorescence spectra of seven phenazines (two belonging to the C2h point group, two to the C2v point group, two to the Cs point group and one to the C1 point group) in organic solvents of varying polarity show a bathochromic shift in all cases. Fluorescence quantum yields increase as the polarity of the solvent increases for the C2h and the Cs compounds, however, no appreciable changes are noted in the C2v compounds. The unexpectedly strong solvent interactions with the two centrosymmetric phenazines are explained on the basis of a localized excited state. This explanation was supported by excited state dipole moment measurements, which indicated similar moments for the C2h and C2v compounds. Two of the compounds undergo lasing when placed in a laser cavity and pumped with the third harmonic of an Nd-YAG laser.

New oxirane derivatives of 1,4-naphthoquinones and their evaluation against T. cruzi epimastigote forms

New oxirane derivatives were synthesized using six naphthoquinones as the starting materials. Our biological results showed that these oxiranes acted as trypanocidal agents against Trypanosoma cruzi with minimal cytotoxicity in the VERO cell line compared to naphthoquinones. In particular, oxirane derivative 14 showed low cytotoxicity in a mammalian cell line and exhibited better activity against epimastigote forms of T.cruzi than the current drug used to treat Chagas disease, benznidazole.

Quinonoid and phenazine compounds: Synthesis and evaluation against H37Rv, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis

Several quinonoid and phenazine compounds were synthesized in moderate to high yields and showed activity against H(37)Rv, rifampicin and isoniazid-resistance strains of Mycobacterium tuberculosis. The cytotoxity of the compounds were evaluated against human peripheral blood mononuclear cells (PBMC) and these substances emerge as promising antitubercular prototypes.