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, Vaînia M.
AU - Alakurtti, Sami
N1 - Publisher Copyright:
© 2016 The American Chemical Society and American Society of Pharmacognosy.
PY - 2016/2/26
Y1 - 2016/2/26
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.
UR - http://www.scopus.com/inward/record.url?scp=84959432533&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.5b00990
DO - 10.1021/acs.jnatprod.5b00990
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C2 - 26849852
AN - SCOPUS:84959432533
SN - 0163-3864
VL - 79
SP - 362
EP - 368
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 2
ER -