Hydrosoluble formazan XTT: its application to natural products drug discovery for Leishmania

Williams, Cornelly; Espinosa, Omar Ariel; Montenegro, Héctor; Cubilla, Luis; Capson, Todd L.; Ortega-Barrı́a, Eduardo; Romero, Luz

doi:10.1016/j.mimet.2003.08.013

Cited by 76 publications

(53 citation statements)

References 10 publications

(13 reference statements)

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“…Indeed, these salts are reduced to soluble derivatives of formazan, and their reduction is accelerated by the addition of an electron-coupling agent, phenazine methosulfate (PMS) (29), thereby increasing test sensitivity. However, although the efficacy of these tests has been demonstrated in sev- eral studies (17,27) for evaluations of the sensitivity of Leishmania to drugs or plant extracts (30), we found that XTT tests displayed a lack of sensitivity with L. guyanensis strains. Furthermore, the presence of PMS may lead to the formation of crystals in the culture medium, modifying the absorbance of the product formed and resulting in erroneous findings (21).…”

Section: Discussionmentioning

confidence: 57%

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Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp

et al. 2014

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In French Guiana, leishmaniasis is an essentially cutaneous infection. It constitutes a major public health problem, with a real incidence of 0.2 to 0.3%. Leishmania guyanensis is the causal species most frequently encountered in French Guiana. The treatment of leishmaniasis is essentially drug based, but the therapeutic compounds available have major side effects (e.g., liver damage and diabetes) and must be administered parenterally or are costly. The efficacy of some of these agents has declined due to the emergence of resistance in certain strains of Leishmania. There is currently no vaccine against leishmaniasis, and it is therefore both necessary and urgent to identify new compounds effective against Leishmania. The search for new drugs requires effective tests for evaluations of the leishmanicidal activity of a particular molecule or extract. Microculture tetrazolium assays (MTAs) are colorimetric tests based on the use of tetrazolium salts. We compared the efficacies of three tetrazolium salts-3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT), and 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium (WST-8)-for quantification of the promastigotes of various species of Leishmania. We found that the capacity of Leishmania to metabolize a tetrazolium salt depended on the salt used and the species of Leishmania. WST-8 was the tetrazolium salt best metabolized by L. guyanensis and gave the best sensitivity.

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Section: Discussionmentioning

confidence: 57%

“…In practice, most of these tetrazolium salts have been found to be of variable efficacy for the quantification of Leishmania (13)(14)(15)(16)(17).…”

Section: Eishmaniasis Is a Disease Caused By A Protozoan Of The Genusmentioning

confidence: 99%

Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp

et al. 2014

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“…The need for new medicines for these diseases is especially critical; three billion people live in affected areas and no safe and effective treatments are available (Trouiller et al 2001;Gelb and Hoi 2002). The assays for these three diseases have been modified such that they use reagents and technologies that are available in Panama and other developing countries (Williams et al 2003). The traditional anti-malaria assays used radioactivity, making their use impractical in a majority of developing countries.…”

Section: Y Springermentioning

confidence: 99%

Linking bioprospecting with sustainable development and conservation: the Panama case

et al. 2007

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The limited international resources for economic aid and conservation can only mitigate poverty and losses of biodiversity. Hence, developing nations must establish the capacity to resolve their problems. Additionally, policy-makers and donors need to obtain scientific input on issues such as global change and ecosystem services. We propose that for nations rich in biodiversity, ecosystem services derived from bioprospecting, or drug discovery, could contribute to economic development. In the case where unstudied samples are shipped abroad for research, the chances of obtaining royalties are infmitesimally small. Therefore developing nations will only realize benefits from bioprospecting through in-country research on their own biodiversity. Policy-makers and donors have failed to appreciate the value of this approach. In order to provide an example of the inherent links between conservation and sustainable economic development, we initiated a drug discovery effort in Panama that emphasizes local benefit. As much of the drug discovery process as possible is conducted in Panamanian laboratories, providing jobs dependent on intact biodiversity and enhancing local research and training. In short, research, plus the spin-offs from research, provide immediate and long-lasting benefits to Panama. The connection between conservation and development has been highlighted in publicity about the project in Panama's urban media. This provides a constructive alternative to the perception the among the urban populace that economic development inevitably competes with conservation. In summary, our program uses biodiversity to promote human health as well as to support research capacity, economic development and conservation within Panama. The program provides an example of the widely recognized but little developed concept of bioprospecting research as an ecosystem service.

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“…All assays were based on inhibition of growth of the parasites by added compounds or extracts, as described previously (Molinar-Toribio et al, 2006 andCorbett et al, 2004;Torres et al, 2003 andWilliams et al, 2003).…”

Section: Assaysmentioning

confidence: 99%

Antiprotozoal Activity of Flavonoid Glycosides Isolated fromClidemia sericea. andMosquitoxylon jamaicense.

Montenegro

González

Ortega-Barrı́a

et al. 2007

Pharmaceutical Biology

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A new O-galloyl-C-glycosylflavone, 2 00 ,6 00 -O-digalloylvitexin (1), along with four known glycosylflavones (2-5) have been isolated from Clidemia sericea D. Don (Melastomataceae), and four other known glycosylflavones (6-9) have been isolated from Mosquitoxylon jamaicense Krug & Urb. (Anacardiaceae). Compound 1, 3, and 6 showed mild antimalarial activity (24 AE 1, 38 AE 2, and 44 AE 1 mM, respectively) against a chloroquine-resistant P. falciparum strain. Additionally, tests against leishmaniasis and Trypanosoma cruzi were made. These compounds were identified by MS, UV, IR, and 1D and 2D NMR data and by comparison with the literature data.

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Hydrosoluble formazan XTT: its application to natural products drug discovery for Leishmania

Cited by 76 publications

References 10 publications

Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp

Comparison of Tetrazolium Salt Assays for Evaluation of Drug Activity against Leishmania spp

Linking bioprospecting with sustainable development and conservation: the Panama case

Antiprotozoal Activity of Flavonoid Glycosides Isolated fromClidemia sericea. andMosquitoxylon jamaicense.

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