Carbaporphyrin ketals as potential agents for a new photodynamic therapy treatment of leishmaniasis

Morgenthaler, Justin B.; Peters, Steven J.; Cedeño, David L.; Constantino, Manuel H.; Edwards, Kevin A.; Kamowski, Erin M.; Passini, Jennifer C.; Butkus, Brian E.; Young, Alexandra M.; Lash, Timothy D.; Jones, Marjorie A.

doi:10.1016/j.bmc.2008.05.037

Cited by 56 publications

(50 citation statements)

References 22 publications

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“…They also produce superoxide in 20% ethanol solutions in proportion to the amount of CKOMe used (see the supplemental material). The production of these species induced by CKOMe inside promastigotes of Leishmania tarentolae was previously demonstrated by Morgenthaler et al (34).…”

Section: Resultsmentioning

confidence: 55%

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In Vitro and In Vivo Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis

Taylor

Cedeño

Muñoz

et al. 2011

Antimicrob Agents Chemother

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Carbaporphyrin ketals are porphyrinoid compounds in which a pyrrole ring of a typical porphyrin macrocycle has been replaced by a ketal-substituted indene ring. It was recently demonstrated that these compounds are effective in vitro against Leishmania tarentolae. Their in vitro effectiveness is increased when they are exposed to visible light; they act as photosensitizers capable of mediating the production of reactive oxygen species (ROS). Following on this evidence, the effectiveness and cytotoxicity of the dimethyl and diethyl carbaporphyrin ketals (CKOMe and CKOEt, respectively) were determined in vitro using pathogenic Leishmania species with and without exposure to visible light (2 and 4 h). The effectiveness against various pathogenic Leishmania species was determined to be in a micromolar range. Additionally, the effect of encapsulating the carbaporphyrin ketals in liposome formulations was tested. Liposomal delivery diminished their toxicity, while the effectiveness was enhanced upon exposure to visible light (photodynamic effect). The cytotoxicity levels for human U937 cells and hamster peritoneal macrophages were in the ranges of 0.3 to 9 M and 7 to 330 M, respectively. When tested in vivo, using a hamster (Mesocricetus auratus) model of cutaneous leishmaniasis, CKOMe was active even in the dark, suggesting that the compound, once metabolized in the animal tissue, produces an active ingredient that does not seem to be photosensitive. Reduction in lesion size, histopathologic analyses, and smears confirmed the in vivo effectiveness of the compound, since the parasitic load was diminished without noticeable toxic effects.

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Section: Resultsmentioning

confidence: 55%

“…These compounds are able to absorb visible and near infrared light, which makes them attractive as photodynamic therapy photosensitizers. Recently, it was demonstrated that the compounds are effective in vitro against promastigotes of Leishmania tarentolae and that their effectiveness is increased when exposed to visible light (34).…”

mentioning

confidence: 99%

In Vitro and In Vivo Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis

Taylor

Cedeño

Muñoz

et al. 2011

Antimicrob Agents Chemother

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“…[64] Oxidations of benzocarbaporphyrins with ferric chloride in the presence of alcohol solvents give carbaporphyrin ketals that have some promise as photosensitizers in PDT and are also being investigated as possible agents for treating leishmaniasis. [66] An initial example of a metalated dicarbaporphyrinoid system also suggests that further structural diversity in these unusual metalloporphyrin analogue systems will be possible.…”

Section: Discussionmentioning

confidence: 99%

“…[64,65] Furthermore, these ketals have been shown to be active against Leishmania and this property could lead to the development of a new treatment for leishmaniasis. [66] Subsequently, we noted that silver(I) acetate smoothly reacted with benzocarbaporphyrins 5 to give the silver(III) derivatives 71. [41,67,68] These nonpolar derivatives are stable aromatic compounds and X-ray crystallography shows that the macrocycle is virtually planar.…”

Section: Metalation Of Carbaporphyrins and Related Macrocyclesmentioning

confidence: 99%

Metalation of Carbaporphyrinoid Systems

Lash¹

2008

MHC

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“…Axenic Leishmania tarentolae promastigote cells (ATCC 30143 cells) were grown, at room temperature, in polystyrene 25 cm 2 flasks (Corning) in sterile brain-heart infusion (BHI; Becton, Dickinson and Company) medium prepared as per the ATCC recommended protocol with added hemin (20 μM), penicillin and streptomycin (10,000 units/mL and 10 mg/mL, respectively; Sigma-Aldrich) following the general protocol of Morgenthaler et al (2008). Although L. tarentolae is not a pathogen for humans, we used this species because the promastigotes are easy to grow in culture and can be used as a model system for the human pathogenic species (Taylor et al, 2010).…”

Section: Cellsmentioning

confidence: 99%

Vanadium Complexes Are in vitro Inhibitors of Leishmania Secreted Acid Phosphatases

Mendez¹,

Dorsey²,

McLauchlan³

et al. 2013

IJC

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Leishmaniasis is a parasitic disease caused by the protozoa Leishmania. These organisms secrete acid phosphatases during their growth cycle as an important part of cell targeting to host macrophage cells thus allowing for a successful infection. Secreted acid phosphatases (SAP) are reported to play a significant role in the survival of Leishmania cells, thus evaluation of these enzymes is of interest. The inhibition of SAP can be the focus of a new drug therapy. We tested for SAP activity from Leishmania tarentolae following the addition of a series of vanadium complexes including decavanadate. Cell cultures at different stages in their growth curve were harvested by centrifugation and supernatant was collected. The SAP activity in the supernatant was assayed with the artificial substrate p-nitrophenylphosphate (pNPP). Incubation with orthovanadate resulted in a decrease in activity of 18% ± 1 relative to the control, in comparison to decavanadate, which resulted in a 35% ± 4 decrease in activity. Other vanadium complexes showed smaller inhibitory effects than orthovanadate. Some vanadium complexes appeared to have an effect on reducing cell clumping when compared to control cells. The SAP was partially isolated through anion exchange chromatography and results indicate that SAP isozyme forms are present in the supernatant from cells. Future work is focused on obtaining recombinant enzyme which can be more completely characterized for inhibition by vanadium complexes.

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Carbaporphyrin ketals as potential agents for a new photodynamic therapy treatment of leishmaniasis

Cited by 56 publications

References 22 publications

In Vitro and In Vivo Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis

In Vitro and In Vivo Studies of the Utility of Dimethyl and Diethyl Carbaporphyrin Ketals in Treatment of Cutaneous Leishmaniasis

Metalation of Carbaporphyrinoid Systems

Vanadium Complexes Are in vitro Inhibitors of Leishmania Secreted Acid Phosphatases

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