Action of pyrazolopyrimidine derivatives on American Leishmania spp. promastigotes

Avila, JoséLuis; Polegre, María Argelia; Ávila, Andrea; Robins, Roland K.

doi:10.1016/0742-8413(86)90124-6

Cited by 28 publications

(25 citation statements)

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“…Various related compounds of pyrazolopyrimidines have antitumor and antileukemic activities [6,7]. Several derivatives such as 4-hydroxypyrazolopyrimidine (allopurin), which are used in the treatment of hyperuricemia and gout, inhibit de novo purine biosynthesis and xanthine oxidase [8].…”

Section: Introductionmentioning

confidence: 99%

“…Cyclization of 5-aminopyrazoles with ketene-S,S and N,S-acetals is the most widely used route for the synthesis of pyrazolopyrimidines [9][10][11][12]. Accordingly, we report in this paper novel synthesis of functionalized pyrazolo [1, 5-a] pyrimidines 4a-b, 5a-c, 6 by the reactions of 5-aminopyrazole 3 with respective 2-[bis (methylthio)methylene]malononitrile 1, ethyl 2-cyano-3,3-bis[methylthio]acrylate, α, α-dicyanoketene-N, S-acetals 2a-c. The antibacterial, antifungal, cytotoxicity testing results of some selected compounds is also included.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-a]pyrimidine from 5-Aminopyrazole Incorporated with p-Chloroaniline

Al‐Adiwish¹,

Shtewi²,

Ashrif³

et al. 2017

AJHC

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-a]pyrimidine from 5-Aminopyrazole Incorporated with p-Chloroaniline

Al‐Adiwish¹,

Shtewi²,

Ashrif³

et al. 2017

AJHC

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“…Its initial purine concentration was identical to that used in our drug inhibitory tests with American Leishmania spp. (9) and T. cruzi (J. L. Avila, M. A. Polegre, and R. K. Robins, Comp. Biochem.…”

Section: Methodsmentioning

confidence: 99%

“…Certain hypoxanthine (17,30), adenine (6,8,9), and inosine (18,20) analogs are biologically active against Leishmania spp., T. cruzi, and T. rangeli (10) culture forms. Because purines reverse the inhibitory activity of these analogs (8,17,18), we examined the biological activity of certain guanine and guanosine analogs on the multiplication of culture forms of Leishmania and Trypanosoma (promastigotes and epimastigotes, respectively) and of mammalian forms of T. cruzi.…”

Section: * Corresponding Authormentioning

confidence: 99%

Biological activity of analogs of guanine and guanosine against American Trypanosoma and Leishmania spp

Avila¹,

Rojas²,

Ávila³

et al. 1987

Antimicrob Agents Chemother

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The growth inhibitory effects of six guanine and guanosine analogs, 3-deazaguanine (compound 1); 3-deazaguanosine (compound 2); 6-aminoallopurinol (compound 3); 9-I-xylofuranosyl guanine (compound 4); a ribosylated derivative of compound 3, 6-aminopyrazolo(3,4-d)pyrimidin-4-one (compound 5); and 5-aminoformycin B (compound 6), were tested against some pathogenic members of the family of American Trypanosomatidae. Compounds 1 and 2 were highly active against Trypanosoma cruzi, Trypanosoma rangeli, and American Leishmania spp. in in vitro culture forms. Both compounds also showed antiprotozoal activity in T. cruzi-infected mice, with the optimal dose being about 30 mg/kg of body weight per day given as 10 consecutive doses. Compound 3 was the most active compound in vitro, inhibiting all of the American Trypanosomatidae culture forms tested. It was also highly inhibitory in mice that were acutely infected with T. cruzi, with the optimal dose being about 10 mg/kg of body weight per day. Ribosylation of compound 3 resulted in a derivative that showed decreased inhibitory activity on Trypanosomatidae multiplication. Compound 6 was highly inhibitory of in vitro multiplication of American Leishmania and T. rangeli but had no effect on T. cruzi epimastigotes and on mice that were acutely infected with T. cruzi. Compound 4 showed only a slight effect on T. cruzi epimastigotes.Recent reviews on the chemotherapy of Chagas' disease and American cutaneous leishmaniasis have emphasized the deficiencies of currently available therapeutic agents and the need for new ones (1, 31). These diseases are still important health problems in the Western Hemisphere, while Trypanosoma rangeli, which is apparently a harmless parasite of humans and a variety of birds and domestic animals, infects about 52% of exposed people in endemic areas (23).With regard to purine metabolism, with the exception of adenine, the incorporation of purine bases by Trypanosoma cruzi is similar to that of Leishmania spp. (11). Because purine bases are incorporated more readily than their respective ribonucleosides, it appears that the major biosynthetic pathway from a purine base to its ribonucleoside is direct, via purine phosphoribosyltransferases, rather than a sequential conversion from base to ribonucleoside to ribonucleotide (11). In contrast to Leishmania spp. (19,22) and African trypanosomes (15), which have very high nucleosidecleaving activities, purine ribonucleosides are remarkably stable in T. cruzi (11).With regard to guanine metabolism in members of the family Trypanosomatidae, data are consistent with a direct conversion of guanine to GMP which could be converted sequentially to IMP and AMP by GMP reductase (EC 1.6.6.8) and the adenylosuccinate synthetase (EC 6.3.4.4) to GTP. For guanosine analogs to reach the nucleotide stage, they must be modified by purine nucleoside-cleaving enzymes, which have been demonstrated in several Trypanosomatidae (16,21,24), to produce the parent heterocyclic compound, which then acts as a substrate for hypoxanthin...

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“…[7][8][9][10][11] We have presumed that by employing hydrazides as the amine components of this reaction, the cascade heterocyclization 2→3→4→5 may occur to afford derivatives of a new heterocyclic system of pyrazolo [4,3- …”

Section: Introductionmentioning

confidence: 99%

Two approaches to a new heterocyclic system of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine

Mezheritsky¹,

Minyarva²,

Tyurin³

et al. 2004

Arkivoc

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Action of pyrazolopyrimidine derivatives on American Leishmania spp. promastigotes

Cited by 28 publications

References 14 publications

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-<i>a</i>]pyrimidine from 5-Aminopyrazole Incorporated with <i>p</i>-Chloroaniline

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-<i>a</i>]pyrimidine from 5-Aminopyrazole Incorporated with <i>p</i>-Chloroaniline

Biological activity of analogs of guanine and guanosine against American Trypanosoma and Leishmania spp

Two approaches to a new heterocyclic system of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine

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Action of pyrazolopyrimidine derivatives on American Leishmania spp. promastigotes

Cited by 28 publications

References 14 publications

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-&lt;i&gt;a&lt;/i&gt;]pyrimidine from 5-Aminopyrazole Incorporated with &lt;i&gt;p&lt;/i&gt;-Chloroaniline

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-&lt;i&gt;a&lt;/i&gt;]pyrimidine from 5-Aminopyrazole Incorporated with &lt;i&gt;p&lt;/i&gt;-Chloroaniline

Biological activity of analogs of guanine and guanosine against American Trypanosoma and Leishmania spp

Two approaches to a new heterocyclic system of pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine

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Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-<i>a</i>]pyrimidine from 5-Aminopyrazole Incorporated with <i>p</i>-Chloroaniline

Synthesis, Biological Activity and Cytotoxicity of New Fused Pyrazolo[1,5-<i>a</i>]pyrimidine from 5-Aminopyrazole Incorporated with <i>p</i>-Chloroaniline