Leishmaniasis– current chemotherapy and recent advances in the search for novel drugs

Croft, Simon L.; Coombs, Graham H.

doi:10.1016/j.pt.2003.09.008

Cited by 752 publications

(566 citation statements)

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“…In Table 1, the positions 3 and 4 are represented by R and R 0 . [21,45]. Most of the drugs available against leishmaniasis are expensive and require a long treatment and are becoming more and more ineffective [9].…”

Section: Antifungal Activitymentioning

confidence: 99%

Quinoxaline, its derivatives and applications: A State of the Art review

Pereira

Moura

Cordeiro

et al. 2015

European Journal of Medicinal Chemistry

366

124

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a b s t r a c tQuinoxaline derivatives are an important class of heterocycle compounds, where N replaces some carbon atoms in the ring of naphthalene. Its molecular formula is C 8 H 6 N 2 , formed by the fusion of two aromatic rings, benzene and pyrazine. It is rare in natural state, but their synthesis is easy to perform.In this review the State of the Art will be presented, which includes a summary of the progress made over the past years in the knowledge of the structure and mechanism of the quinoxaline and quinoxaline derivatives, associated medical and biomedical value as well as industrial value.Modifying quinoxaline structure it is possible to obtain a wide variety of biomedical applications, namely antimicrobial activities and chronic and metabolic diseases treatment.

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Section: Antifungal Activitymentioning

confidence: 99%

Quinoxaline, its derivatives and applications: A State of the Art review

Pereira

Moura

Cordeiro

et al. 2015

European Journal of Medicinal Chemistry

366

124

View full text Add to dashboard Cite

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“…Some compounds did not show any noticeable toxicity with this method (2, 7, 16, 17 and 20), and no apparent structure-activity relationship was observed between toxicity for the J774 cells and the compound subgroup (that is, derivatives having C-3 ketone carbonyl: compounds 10 and 11 were toxic, but L-aspartyl amide of betulinic acid 12 was non-toxic). However, all betulin derivatives having both hydroxyl groups acetylated (6,16,17,18) were non-toxic to J774 cells. It is noticeable that even betulin 1 exhibited certain toxicity (18.4 ± 0.4% inhibition).…”

Section: Antileishmanial Activity Of Betulin Derivatives L Wert Et Almentioning

confidence: 90%

“…All the compounds assayed were able to reduce the multiplication of intracellular amastigotes of Leishmania as compared with the uninfected control cultures (Table 4). In the subgroup of simple betulin derivatives (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), only four compounds (1, 2, 6 and 12) were tested against intracellular L. infantum and L. donovani amastigotes. Betulin 1 showed best activity (49.3 and 42.8%, respectively), whereas rest of the compounds showed similar or decreased activity.…”

Section: Effect Of Betulin Derivatives On Leishmania Amastigotes In Mmentioning

confidence: 99%

“…A large number of drugs have been used, but the therapeutics of leishmaniasis is hampered by the toxicity of some of the compounds, difficulties in administration in remote areas, the intraspecific variability of Leishmania drug sensitivities and the development of resistances, particularly in the case of L. donovani in India. 6,7 Moreover, in many countries, the use of first-line drugs (antimonials and amphotericins) is precluded by their high price. 8 Despite impressive advances in the understanding of the biology and molecular biology of Leishmania spp, these have not yielded any substantial improvements on chemotherapy; generally speaking, the compounds either already in use or undergoing clinical trials are incidental findings rather than the result of a directed research effort.…”

Section: Introductionmentioning

confidence: 99%

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Toxicity of betulin derivatives and in vitro effect on promastigotes and amastigotes of Leishmania infantum and L. donovani

et al. 2011

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The toxicity and antileishmanial activity of 20 betulin derivatives were studied. The toxicity of betulin and synthesized compounds was determined using a bacterial test (Microtox) and two mammalian cell lines (CHO-K1 and J774). The antileishmanial activity of compounds (50 lM) was examined in both the promastigote and intracellular amastigote stages of Leishmania infantum and L. donovani. No correlation was found among the toxicity tests. All the compounds showed significant antipromastigote activity. The antiproliferative capacity of derivatives was dependent on the parasite stage studied, and no substantial differences were found between Leishmania species. Betulin, 3,28-di-O-acetylbetulin and L-aspartyl amide of betulonic acid showed moderate activity against amastigotes. The highest inhibition of intracellular amastigote multiplication was achieved with a low micromolar concentration (IC 50 ca 9 lM) of heterocyclic betulin derivative 3,28-di-O-acetyllup-13(18)-ene with N-ethyltriazolo moiety 16, without significant toxicity for mammalian cells. These results point to the interest of this lead compound for further in vitro and in vivo tests.

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“…En la actualidad, cada vez son más los estudios que reportan el hallazgo de Leishmania spp. resistente al antimonio pentavalente alrededor del mundo y en Colombia (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Como tratamientos de segunda línea se utilizan la anfotericina B, la pentamidina y la miltefosina, que son medicamentos efectivos contra la leishmaniasis, pero, debido a sus altos costos y los efectos secundarios que pueden ocasionar, estos son poco utilizados (18).…”

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