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Natural product-based drug design: novel compounds against Leishmania (L.) infantum


Natural products in the era of rational drug design still play an important role in the search for new active drugs, representing valuable lead structures that can be developed further into useful therapeutics. Prof. Tempone group together with Prof. João H. G. Lago (UNIFESP) have shown the in vitro potential of natural products gibbilimbol and polygodial from Brazilian plants Piper malacophyllum and Drimys brasiliensis, respectively, against Leishmania infantum. Other semi-synthetic derivatives of the sesquiterpene polygodial such as drimendiol and drimendiol acetate were prepared and displayed in vitro potential, but with reduced toxicity. Similarly, the phenol derivative gibbilimbol was obtained and displayed activity against amastigote forms of L. (L.) infatum. Finally, a selective antileishmanial polyketide isolated from a Brazilian marine sponge (plakortide P), will also be considered for synthesis. Due to the structural characteristics of these compounds, several new derivatives could be prepared, aiming the development of pharmacologically active compounds with low toxicity. Considering the importance of natural products as drug prototypes, we expect to select novel derivatives with more activity against the parasite and less toxicity against mammalian cells. The in vitro lethal action and the immunomodulatory activity studies to be performed together with Prof. Abhay Satoskar and Dr. Fuchs groups at Ohio will provide important information for further drug design studies against Leishmaniasis. (AU)

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(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
DA COSTA-SILVA, THAIS ALVES; GRECCO, SIMONE S.; DE SOUSA, FERNANDA S.; LAGO, JOAO HENRIQUE G.; MARTINS, EUDER G. A.; TERRAZAS, CESAR A.; VARIKUTI, SANJAY; OWENS, KATHERINE L.; BEVERLEY, STEPHEN M.; SATOSKAR, ABHAY R.; TEMPONE, ANDRE G. Immunomodulatory and Antileishmanial Activity of Phenylpropanoid Dimers Isolated from Nectandra leucantha. Journal of Natural Products, v. 78, n. 4, p. 653-657, APR 2015. Web of Science Citations: 23.

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