Practical modalities for prevention of fungal infections in cancer patients

Pauw, B.E. de

doi:10.1007/bf01575119

Cited by 36 publications

(16 citation statements)

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“…leukaemia) or therapeutic procedures (e.g. broad spectrum antibiotics, immuno-suppression prior to organ transplantation) (De Pauw, 1997). The yeast Candida albicans is an opportunistic fungal pathogen which causes a range of diseases in susceptible individuals (Pfaller et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes

Coyle

Kinsella

McCann

et al. 2004

Toxicology in Vitro

102

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1,10-Phenanthroline (phen) and metal-phen complexes display fungicidal and fungiststic activity, disrupt mitochondrial function and induce oxidative stress. We have examined the effect of these drugs on the structure of yeast and mammalian cell organelles and the integrity of cellular DNA. Exposure of Candida albicans to [Mn(phen) 2 (mal)].2H 2 O or [Ag 2 (phen) 3 (mal)].2H 2 O (mal H 2 =malonic acid) resulted in DNA degradation whereas exposure to phen or [Cu(phen) 2 (mal)].2H 2 O did not. All drugs induced extensive changes to the internal structure of yeast cells including retraction of the cytoplasm, nuclear fragmentation and disruption of the mitochondrion. In the case of cultured mammalian cells [Cu(phen) 2 (mal)].2H 2 O induced apoptosis as evidenced by the ladder pattern of DNA fragments following gel electrophoresis and also the blebbing of the cell membrane. The other drugs produced non-specific DNA degradation in mammalian cells. In conclusion, phen and metal-phen complexes have the potential to induce apoptosis in fungal and mammalian cells. Given their distinct mode of action compared to conventional anti-fungal drugs, phen and metal-phen complexes may represent a novel group of anti-fungal agents for use either in combination with existing drugs or in cases where resistance to conventional drugs has emerged. #

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Section: Introductionmentioning

confidence: 99%

Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes

Coyle

Kinsella

McCann

et al. 2004

Toxicology in Vitro

102

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“…Both nC=N and nCS 2 bands were split in the spectra of 1, 2 and 4, and broadened in the spectrum of 3. These findings point to an asymmetric coordination of the dithiocarbimate to the zinc(II) by the two sulphur atoms forming a ZnS 4 distorted tetrahedral environment as observed for (Bu 4 N) 2 [Zn(4-XC 6 H 4 SO 2 N=CS 2 ) 2 ]. 11 All the new substances were active against C. Gloeosporioides whereas no activity was observed against C. albicans or C. tropicalis.…”

Section: Discussionmentioning

confidence: 63%

“…The spectrum of 3 showed a broad band in this region. These bands were assigned to the n as CS 2 and are shifted to lower wavenumbers with respect to the spectra of the ligands. [18][19][20] The positions observed for the n as CS 2 and nCN bands in the spectra of the compounds studied here were consistent with the complexation of the dithiocarbimate group by two sulfur atoms.…”

Section: Chemistrymentioning

confidence: 99%

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Syntheses, characterization and antifungal activity of tris(1,10-phenanthroline)iron(ii) bis(n-r-sulfonyldithiocarbimate)zincate(ii)

Bottega¹,

Oliveira²,

Garcia³

et al. 2013

Quím. Nova

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Recebido em 24/8/12; aceito em 7/1/13; publicado na web em 24/5/13Four new compounds with the general formula [Fe(phen) 3 ][Zn(RSO 2 N=CS 2 ) 2 ], where phen = 1,10-phenanthroline, R = 4-FC 6 H 4 (1), 4-ClC 6 H 4 (2), 4-BrC 6 H 4 (3) and 4-IC 6 H 4 (4), respectively, were obtained by the reaction of the appropriate potassium N-R-sulfonyldithiocarbimate (RSO 2 N=CS 2 K 2 ) and tris(1,10-phenanthroline)iron(II) sulfate, with zinc(II) acetate dihydrate in dimethylformamide. The elemental analyses and the IR data were consistent with the formation of the expected complexes salts. The 1 H and 13 C NMR spectra showed the signals for the cationic iron(II) complex and dithiocarbimate moieties. The molar conductance data were consistent with the 1:1 cation:anion complexes in 1-4. The antifungal activities of the compounds were tested in vitro against Candida albicans, Candida tropicalis and Colletotrichum gloeosporioides.Keywords: dithiocarbimates; metal complexes; antifungal activity. INTRODUCTIONFungal infections in humans have increased in recent years predominantly affecting immunocompromised patients. 1,2 Fungi from the Candida genus can infect the oral and vaginal cavities, skin and, more seriously, essential organs. 1,3 Colletotrichum gloeosporioides is known to infect a wide variety of hosts, including vegetables, field and forage crops, fruit trees, and ornamental shrubs. 4 C. gloeosporioides infections in humans can cause keratitis in healthy or immunocompromised individuals and can induce phaeohyphomycosis in patients with hematologic malignancies and iatrogenic immunosuppression. [5][6][7] Several dithiocarbamate and N-substituted dithiocarbamate complexes and salts (Scheme 1a) have been used as agrochemicals mainly due to their high efficiency in controlling plant fungal diseases, and their relatively low toxicity. 8,9 The literature reports that dithiocarbamate complexes are also active against Candida spp. 10In recent studies, we have demonstrated that the dithiocarbimate compounds A 2 [Zn(RSO 2 N=CS 2 ) 2 ] and A 2 [Sn(Bu) 2 (RSO 2 N=CS 2 ) 2 ] (A = tetrabutylammonium cation or tetraphenylphosphanium cation, Bu = n-butyl and R = 4-FC 6 H 4 , 4-ClC 6 H 4 , 4-BrC 6 H 4 and 4-IC 6 H 4 ) are active against Colletotrichum gloeosporioides. 11-13 It was also observed that the cations Bu 4 N + and Ph 4 P + were inactive.Unlike dithiocarbamate analogues, the bis(dithiocarbimate) metal(II) complexes are anionic species (Scheme 1), offering potentially useful modulation of this activity. For example, enhanced antifungal activity should be possible either by the use of active counter ions, or by varying the solubility of the salts of the complexes through the use of different cations.Considering these possibilities, the activities of some salts were tested in order to find an appropriate active cation to deepen the investigation into the antifungal potential of dithiocarbimates. This search revealed that tris(phenantholine)iron(II) perchlorate is active against Colletotrichum gloeosporioides. Here we describe the s...

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“…For many candidal infections fluconazole is now an attractive alternative option provided that involvement of resistant species is unlikely [6,7]. Fluconazole has superseded ketoconazole and is now widely used in the prophylaxis and treatment of both invasive and mucocutaneous candidosis as well as cryptococcosis [8,9]. Itraconazole which is only available for oral administration has been widely accepted for the treatment of blastomycosis, histoplasmosis, sporotrichosis and non-acute forms of aspergillosis.…”

Section: Introductionmentioning

confidence: 99%

The Challenge of Invasive Fungal Infection

Pauw

Meunier²

1999

Chemotherapy

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Systemic fungal infections cause almost 25% of the infection-related deaths in leukaemic patients. Particularly those with prolonged neutropenia are at risk but mycoses also feature in critically ill intensive care patients and in individuals who are treated for solid tumours and AIDS, or who received an organ transplant. The spread of AIDS and the more aggressive cytotoxic chemotherapy in combination with an improved management of haemorrhages and bacterial infections in leukaemic and other cancer patients facilitated the occurrence of these invasive fungal infections. These life-threatening complications remain both difficult to diagnose and to treat and therefore carry a poor prognosis. For many years, the only realistic option to treat systemic infections was amphotericin B, whose administration was known to be associated with numerous adverse effects. Now less toxic formulations of amphotericin have become available for clinical use, as well as several new triazoles that appear to provide an effective and less toxic alternative for the treatment of certain fungal infections.

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Practical modalities for prevention of fungal infections in cancer patients

Cited by 36 publications

References 41 publications

Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes

Induction of apoptosis in yeast and mammalian cells by exposure to 1,10-phenanthroline metal complexes

Syntheses, characterization and antifungal activity of tris(1,10-phenanthroline)iron(ii) bis(n-r-sulfonyldithiocarbimate)zincate(ii)

The Challenge of Invasive Fungal Infection

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