Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi

Minni Pirttimaa, Abedelmajeed Nasereddin, Dmitry Kopelyanskiy, Marcel Kaiser, Jari Yli-Kauhaluoma, Kirsi-Marja Oksman-Caldentey, Reto Brun, Charles L. Jaffe, Vânia M. Moreira (Corresponding Author), Sami Alakurtti

Research output: Contribution to journalArticleScientificpeer-review

18 Citations (Scopus)

Abstract

Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 µM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 µM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 µM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.
Original languageEnglish
Pages (from-to)362-368
JournalJournal of Natural Products
Volume79
Issue number2
DOIs
Publication statusPublished - 2016
MoE publication typeA1 Journal article-refereed

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Abietane Diterpenes
Leishmania donovani
Diterpenes
Trypanosoma cruzi
Amides
Inhibitory Concentration 50
Macrophages
Cytotoxicity
Leishmaniasis
Chagas Disease
Libraries
Parasites
Pharmaceutical Preparations
Growth
dehydroabietylamine

Cite this

Pirttimaa, Minni ; Nasereddin, Abedelmajeed ; Kopelyanskiy, Dmitry ; Kaiser, Marcel ; Yli-Kauhaluoma, Jari ; Oksman-Caldentey, Kirsi-Marja ; Brun, Reto ; Jaffe, Charles L. ; Moreira, Vânia M. ; Alakurtti, Sami. / Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi. In: Journal of Natural Products. 2016 ; Vol. 79, No. 2. pp. 362-368.
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title = "Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi",
abstract = "Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 µM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 µM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 µM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.",
author = "Minni Pirttimaa and Abedelmajeed Nasereddin and Dmitry Kopelyanskiy and Marcel Kaiser and Jari Yli-Kauhaluoma and Kirsi-Marja Oksman-Caldentey and Reto Brun and Jaffe, {Charles L.} and Moreira, {V{\^a}nia M.} and Sami Alakurtti",
year = "2016",
doi = "10.1021/acs.jnatprod.5b00990",
language = "English",
volume = "79",
pages = "362--368",
journal = "Journal of Natural Products",
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Pirttimaa, M, Nasereddin, A, Kopelyanskiy, D, Kaiser, M, Yli-Kauhaluoma, J, Oksman-Caldentey, K-M, Brun, R, Jaffe, CL, Moreira, VM & Alakurtti, S 2016, 'Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi', Journal of Natural Products, vol. 79, no. 2, pp. 362-368. https://doi.org/10.1021/acs.jnatprod.5b00990

Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi. / Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L.; Moreira, Vânia M. (Corresponding Author); Alakurtti, Sami.

In: Journal of Natural Products, Vol. 79, No. 2, 2016, p. 362-368.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi

AU - Pirttimaa, Minni

AU - Nasereddin, Abedelmajeed

AU - Kopelyanskiy, Dmitry

AU - Kaiser, Marcel

AU - Yli-Kauhaluoma, Jari

AU - Oksman-Caldentey, Kirsi-Marja

AU - Brun, Reto

AU - Jaffe, Charles L.

AU - Moreira, Vânia M.

AU - Alakurtti, Sami

PY - 2016

Y1 - 2016

N2 - Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 µM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 µM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 µM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

AB - Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 µM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 µM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 µM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

U2 - 10.1021/acs.jnatprod.5b00990

DO - 10.1021/acs.jnatprod.5b00990

M3 - Article

VL - 79

SP - 362

EP - 368

JO - Journal of Natural Products

JF - Journal of Natural Products

SN - 0163-3864

IS - 2

ER -