grandisin has been researched along with galgravin* in 2 studies
2 other study(ies) available for grandisin and galgravin
| Article | Year |
|---|---|
Design and synthesis of a new series of 3,5-disubstituted isoxazoles active against Trypanosoma cruzi and Leishmania amazonensis.
Chagas disease and leishmaniasis are neglected tropical diseases (NTDs) endemic in developing countries. Although there are drugs available for their treatment, efforts on finding new efficacious therapies are continuous. The natural lignans grandisin (1) and veraguensin (2) show activity against trypomastigote T. cruzi and their scaffold has been used as inspiration to design new derivatives with improved potency and chemical properties. We describe here the planning and microwave-irradiated synthesis of 26 isoxazole derivatives based on the structure of the lignans 1 and 2. In addition, the in vitro evaluation against culture trypomastigotes and intracellular amastigotes of T. cruzi and intracellular amastigotes of L. amazonensis and L. infantum is reported. Among the synthesized derivatives, compounds 17 (IC Topics: Animals; Antiprotozoal Agents; Drug Design; Furans; Isoxazoles; Leishmania infantum; Leishmania mexicana; Leishmaniasis; Lignans; Molecular Structure; NADH, NADPH Oxidoreductases; Parasitic Sensitivity Tests; Structure-Activity Relationship; Trypanosoma cruzi | 2017 |
Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.
Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities. Topics: Animals; Antiprotozoal Agents; Furans; Humans; Leishmania; Leishmaniasis; Lignans; Macrophages; Nitric Oxide; Structure-Activity Relationship | 2016 |