TY - JOUR
T1 - Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha
AU - Costa-Silva, Thais Alves Da
AU - Grecco, Simone S.
AU - De Sousa, Fernanda S.
AU - Lago, João Henrique G.
AU - Martins, Euder G.A.
AU - Terrazas, César A.
AU - Varikuti, Sanjay
AU - Owens, Katherine L.
AU - Beverley, Stephen M.
AU - Satoskar, Abhay R.
AU - Tempone, Andre G.
N1 - Publisher Copyright:
© 2015 The American Chemical Society and American Society of Pharmacognosy.
PY - 2015/4/24
Y1 - 2015/4/24
N2 - Three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1-3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 μM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 μM, whereas compound 2 demonstrated a CC50 value of 111.2 μM. Compounds 1-3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis. (Graph Presented).
AB - Three phenylpropanoid dimers (1-3) including two new metabolites were isolated from the extract of the twigs of Nectandra leucantha using antileishmanial bioassay-guided fractionation. The in vitro antiparasitic activity of the isolated compounds against Leishmania donovani parasites and mammalian cytotoxicity and immunomodulatory effects were evaluated. Compounds 1-3 were effective against the intracellular amastigotes within macrophages, with IC50 values of 26.7, 17.8, and 101.9 μM, respectively. The mammalian cytotoxicity, given by the 50% cytotoxic concentration (CC50), was evaluated against peritoneal macrophages. Compounds 1 and 3 were not toxic up to 290 μM, whereas compound 2 demonstrated a CC50 value of 111.2 μM. Compounds 1-3 also suppressed production of disease exacerbatory cytokines IL-6 and IL-10 but had minimal effect on nitric oxide production in L. donovani-infected macrophages, indicating that antileishmanial activity of these compounds is mediated via an NO-independent mechanism. Therefore, these new natural products could represent promising scaffolds for drug design studies for leishmaniasis. (Graph Presented).
UR - https://www.scopus.com/pages/publications/84928786397
U2 - 10.1021/np500809a
DO - 10.1021/np500809a
M3 - Article
C2 - 25835647
AN - SCOPUS:84928786397
SN - 0163-3864
VL - 78
SP - 653
EP - 657
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 4
ER -