Antileishmanial activities of dihydrochalcones from piper elongatum and synthetic related compounds. Structural requirements for activity.
Two dihydrochalcones (1 and 2) were isolated from Piper elongatum Vahl by activity-guided fractionation against extracellular promastigotes of Leishmania braziliensis in vitro. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments. Derivatives 3-7 and 20 synthetic related compounds (8-27) were also assayed to establish the structural requirements for antileishmanial activity. Compounds 1-11 that proved to be more active that ketoconazol, used as positive control, were further assayed against promastigotes of Leishmania tropica and Leishmania infantum. Compounds 7 and 11, with a C(6)-C(3)-C(6) system, proved to be the most promising compounds, with IC(50) values of 2.98 and 3.65 microg/mL, respectively, and exhibited no toxic effect on macrophages (around 90% viability). Correlation between the molecular structures and antileishmanial activity is discussed in detail.
Hermoso
Alicia
A
Departamento de Parasitología, Ecología y Genética, Facultad de Farmacia, Universidad de La Laguna, Avda. Francisco Sánchez s/n, La Laguna, 38206 Tenerife, anary Islands, Spain.
Jiménez
Ignacio A
IA
Mamani
Zulma A
ZA
Bazzocchi
Isabel L
IL
Piñero
José E
JE
Ravelo
Angel G
AG
Valladares
Basilio
B
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D047188:Chalcones; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects* / Q000254:growth & development; D007892:Leishmania braziliensis; D008264:Macrophages / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D021261:Parasitic Sensitivity Tests; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D047188:Chalcones; D010936:Plant Extracts; D002599:Chalcone; C015812:dihydrochalcone