Indole-3-glyoxyl tyrosine: synthesis and antimalarial activity against Plasmodium falciparum

Author(s)

Vasconcelos, Stanley N. S. ^[1] ; Meissner, Kamila A. ^[2] ; Ferraz, Witor R. ^[1] ; Trossini, Gustavo H. G. ^[1] ; Wrenger, Carsten ^[2] ; Stefani, Helio A. ^[1]

Affiliation

^[1] Univ Sao Paulo, Dept Farm, Fac Ciencias Farmaceut, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Unit Drug Discovery, Dept Parasitol, Inst Ciencias Biomed, Sao Paulo - Brazil

• Document type: Journal article
• Source: Future Medicinal Chemistry; v. 11, n. 6, p. 525-538, MAR 2019.
• Web of Science Citations: 2

Abstract

Aim: More than 40% of the world's population, across 105 countries, live in malaria endemic areas. It is estimated that about 500million cases of malaria and half a million deaths occur per year. Results: Herein, we demonstrate the biological activity of indole-3-glyoxyl tyrosine against Plasmodium falciparum, which is the causal agent of the most virulent form of malaria in humans. We developed an efficient synthesis of indole-3-glyoxyl tyrosine derivatives, which were then used as key intermediates in the synthesis of functionalized indole-3-glyoxyl biphenyl tyrosines. Conclusion: In biological testing, the compounds exhibited a parasite growth inhibition of over 85%. A cell viability assay showed low cytotoxicity against human cells, with no significant changes in cell viability, making these compounds potential antimalarials. (AU)

• FAPESP's process: 13/17960-7 - Functionalization of 3-iodo-(L)-Tyrosine via Suzuki-Miyaura Reaction Using Potassium Organotrifluoroborate salts
• Grantee: Stanley Nunes Siqueira Vasconcelos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 12/12807-3 - Analysis of the redox status and its effect on the proliferation of Plasmodium falciparum in genetically different erythrocytes
• Grantee: Kamila Anna Meissner
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/26722-8 - Drug discovery against human infectious diseases
• Grantee: Carsten Wrenger
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/00424-2 - Synthesis of small libraries using potassium Organotrifluoroborates in Suzuki-Miyaura reactions
• Grantee: Helio Alexandre Stefani
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/25543-8 - Medicinal Chemistry strategies (LBDD and SBDD) in the search of tripanomatides sirtuin 2 inhibitors
• Grantee: Gustavo Henrique Goulart Trossini
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/24790-9 - Dissecting Plasmodium falciparum EXP1/GST2 for xenobiotic defence in glucose-6-phosphate dehydrogenase deficiency
• Grantee: Kamila Anna Meissner
• Support Opportunities: Scholarships in Brazil - Post-Doctoral