Synthesis and evaluation of the activity of substituted alkylphenols in Trypanosoma cruzi

• Grant number: 16/00195-4
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): August 01, 2016
• Effective date (End): March 31, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: João Paulo dos Santos Fernandes
• Grantee: Marina Themoteo Varela
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

Chagas disease, also known as American tripanosomiasis, is among the list of WHO as top 3 most important parasitary diseases considered as neglected. The infection is caused by Trypanosoma cruzi, an obligatory intracelular parasite transmitted mainly by the Triatoma infestans and responsible for about 14.000 deaths every year in Latin America. Nowadays only two drugs are available to treat the disease, benznidazole and nifurtimox, which possess significant efficacy in acute phase of the infection, frequently not diagnosed. Natural products derivatives have been widely studied aiming to obtain new chemical entities with antiparasitary acitivty, and possibly new drug candidates. Gibbilimbol B, isolated from leaves of Piper malacophyllum, have shown promissing results against the trypomastigotes of the parasite, with IC50 10-fold higher than the reference drug, benznidazole. Recently, we synthesized and tested six gibbilimbol analogues against trypomastigotes and amastigotes of T. cruzi, showing superior activity in comparison to gibbilimbol B. Therefore, in continuation to our previous work, this project propose 18 additional gibbilimbol analogues to define the role of substitution in the aromatic ring in the antitrypanosomal activity, as well as its cytotoxic activity in mammalian cells, to define the SAR rules. The parent characteristics from gibbilimbol B (substituted aromatic ring and lipophilic lateral chain) were maintained. (AU)

Scientific publications

(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)

VARELA, MARINA THEMOTEO; FERNANDES, JOAO PAULO S.. Natural Products: Key Prototypes to Drug Discovery against Neglected Diseases Caused by Trypanosomatids. Current Medicinal Chemistry, v. 27, n. 13, p. 2133-2146, 2020. (16/25028-3, 16/00195-4)

VARELA, MARINA T.; ROMANELI, MAIARA M.; LIMA, MARTA L.; BORBOREMA, SAMANTA E. T.; TEMPONE, ANDRE G.; FERNANDES, JOAO P. S.. Antiparasitic activity of new gibbilimbol analogues and SAR analysis through efficiency and statistical methods. European Journal of Pharmaceutical Sciences, v. 122, p. 31-41, SEP 15 2018. (16/25028-3, 15/23403-9, 16/00195-4)

VARELA, MARINA T.; LIMA, MARTA L.; GALUPPO, MARIANA K.; TEMPONE, ANDRE G.; DE OLIVEIRA, ALBERTO; LAGO, JOAO HENRIQUE G.; FERNANDES, JOAO PAULO S.. New alkenyl derivative from Piper malacophyllum and analogues: Antiparasitic activity against Trypanosoma cruzi and Leishmania infantum. CHEMICAL BIOLOGY & DRUG DESIGN, v. 90, n. 5, p. 1007-1011, NOV 2017. (12/18756-1, 13/50228-8, 15/11936-2, 16/00195-4)