Synthesis and evaluation of the activity of substituted alkylphenols in Trypanosom...
| Full text | |
| Author(s): |
Varela, Marina T.
[1]
;
Lima, Marta L.
[2, 3]
;
Galuppo, Mariana K.
[2]
;
Tempone, Andre G.
[2]
;
de Oliveira, Alberto
[4]
;
Lago, Joao Henrique G.
[5]
;
Fernandes, Joao Paulo S.
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Fed Sao Paulo, Dept Ciencias Farmaceut, Diadema, SP - Brazil
[2] Adolfo Lutz Inst, Ctr Parasitol & Micol, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, Inst Med Trop Sao Paulo, Sao Paulo, SP - Brazil
[4] Univ Fed Uberlandia, Inst Quim, Uberlandia, MG - Brazil
[5] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP - Brazil
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | CHEMICAL BIOLOGY & DRUG DESIGN; v. 90, n. 5, p. 1007-1011, NOV 2017. |
| Web of Science Citations: | 8 |
| Abstract | |
Alkylphenols isolated from Piper malacophyllum (Piperaceae), gibbilimbols A and B, showed interesting activity against the parasites Trypanosoma cruzi and Leishmania infantum. In continuation to our previous work, a new natural product from the essential oil of the leaves of P.malacophyllum was isolated, the 5-{[}(3E)-oct-3-en-1-il]-1,3-benzodioxole, and also a new set of five compounds was prepared. The antiparasitic activity of the natural product was evaluated in vitro against these parasites, indicating potential against the promastigote/trypomastigote/amastigote forms (IC50 32-83m) of the parasites and low toxicity (CC50>200m) to mammalian cells. The results obtained to the synthetic compounds indicated that the new derivatives maintained the promising antiparasitic activity, but the cytotoxicity was considerably lowered. The amine derivative LINS03011 displayed the most potent IC50 values (13.3 and 16.7m) against amastigotes of T.cruzi and L.infantum, respectively, indicating comparable activity to the phenolic prototype LINS03003, with threefold decreased (CC50 73.5m) cytotoxicity, leading the selectivity index (SI) towards the parasites up to 24.5. In counterpart, LINS03011 has not shown membrane disruptor activity in SYTOX Green model. In summary, this new set showed the hydroxyl is not essential for the antiparasitic activity, and its substitution could decrease the toxicity to mammalian cells. (AU) | |
| FAPESP's process: | 15/11936-2 - Use of chemodiversity of plant species in remaining areas of Atlantic Forest from São Paulo State in the selection of biologically active prototypes |
| Grantee: | João Henrique Ghilardi Lago |
| Support type: | Regular Research Grants |
| FAPESP's process: | 13/50228-8 - Biodiversity components, and its metabolic characters, of Brazilian Islands |
| Grantee: | Roberto Gomes de Souza Berlinck |
| Support type: | BIOTA-FAPESP Program - Thematic Grants |
| FAPESP's process: | 16/00195-4 - Synthesis and evaluation of the activity of substituted alkylphenols in Trypanosoma cruzi |
| Grantee: | Marina Themoteo Varela |
| Support type: | Scholarships in Brazil - Master |
| FAPESP's process: | 12/18756-1 - Evaluation of novel alternative therapies with synthetic drugs using in vitro and experimental models of Leishmania (L.) infantum chagasi |
| Grantee: | André Gustavo Tempone Cardoso |
| Support type: | Regular Research Grants |