Structural and spectroscopic characterization of epiisopiloturine-metal complexes, and anthelmintic activity vs. S-mansoni

Author(s):Show less -

Portes, Marcelo Cecconi ^[1] ; De Moraes, Josue ^[2] ; Costa Veras, Leiz Maria ^[3] ; Leite, Jose Roberto ^[3] ; Mafud, Ana Carolina ^[4] ; Mascarenhas, Yvonne Primerano ^[4] ; Virgino Luz, Adamor Eleiel ^[5] ; Dalmatti Alves De Lima, Filipe Camargo ^[5] ; Do Nascimento, Rafael Rodrigues ^[5] ; Petrilli, Helena Maria ^[5] ; Silva Pinto, Pedro Luiz ^[6] ; Althoff, Gerhard ^[7] ; Da Costa Ferreira, Ana Maria ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, Sao Paulo - Brazil

^[2] Nucleo Pesquisas Doencas Negligenciadas, Fac Ciencias Guarulhos FACIG, Guarulhos - Brazil

^[3] Univ Fed Piaui, BIOTEC, Nucleo Pesquisa Biodiversidade & Biotecnol, Campus Parnaiba, Parnaiba - Brazil

^[4] Univ Sao Paulo, Inst Fis Sao Carlos, Dept Fis & Ciencia Interdisciplinar, Sao Carlos, SP - Brazil

^[5] Univ Sao Paulo, Inst Fis, Dept Fis Mat & Mecan, CP 20516, BR-01498 Sao Paulo - Brazil

^[6] Adolfo Lutz Inst, Nucleo Enteroparasitas, Sao Paulo - Brazil

^[7] NMR Applicat Grp, Bruker Instruments, Rheinstetten - Germany

• Document type: Journal article
• Source: Journal of Coordination Chemistry; v. 69, n. 10, p. 1663-1683, 2016.
• Web of Science Citations: 2

Abstract

Epiisopiloturine (EPI), extracted from leaves of Pilocarpus microphyllus, a plant originally from the Amazon and Savanna regions in Brazil, was described as a potential drug against Schistosomiasis, a neglected severe disease. Herein, EPI was complexed with copper(II) or zinc(II) salts and the isolated species, {[}Cu(epi)(4)](ClO4)(2) (1) and {[}Zn(epi)(2)Cl-2] (2), were structurally and spectroscopically characterized. By using X-ray diffraction, the crystal structures of both metal complexes were determined, indicating a square pyramidal geometry for copper for 1 and a tetrahedral environment around zinc for 2. EPR spectra of 1 show a typical tetragonal environment around the central metal ion with some tetrahedral distortion, both in the solid state and in frozen acetonitrile solution, in accordance with crystallographic data. For 2, NMR spectra have bands consistent with a tetrahedral species in solid state or in DMSO-d(6) solution. These spectroscopic characterization data were further supported by Density Functional Theory calculations, showing that these metal complexes are also stable in solution. Those metal complexes were tested against adult worms of Schistosoma mansoni, in comparison to the free alkaloid as anthelmintic agent. Coordination with copper(II) improved the alkaloid schistosomicidal properties, while binding to zinc(II) decreased its activity. {[}GRAPHICS] . (AU)

• FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
• Grantee: Ana Maria da Costa Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/02282-6 - Structure-activity relationship studies about of Pilocarpus microphyllus (Rutaceae) alkaloid derivatives against Schistosoma mansoni
• Grantee: Ana Carolina Mafud
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/02326-8 - Computational modeling of solid-molecule interaction in systems with nanotechnology interests
• Grantee: Filipe Camargo Dalmatti Alves Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC