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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Synthesis, characterization, and anticancer activity of folate gamma-ferrocenyl conjugatest

Full text
Author(s):
Bertuzzi, Diego L. [1] ; Perli, Gabriel [1] ; Braga, Carolyne B. [1] ; Ornelas, Catia [1]
Total Authors: 4
Affiliation:
[1] Univ Estadual Campinas, Unicamp, Inst Chem, BR-13083861 Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: NEW JOURNAL OF CHEMISTRY; v. 44, n. 12, p. 4694-4703, MAR 28 2020.
Web of Science Citations: 0
Abstract

The quest for alternative therapeutic agents with safe and effective profiles is one of the biggest challenges in oncology. FoLate-targeted therapy can deliver drugs selectively into maLignant ceLLs via the Fra receptor, whereas bioorganometaic chemistry offers potentiaL new drug candidates. Herein, novel foLate ry-ferrocene (ry-Fc) conjugates were synthesized through a regiospecific route by reacting amino terminated glutamate (au) ry-Fc residues with pteroyE azide (68-78% yield), and their in vitro anticancer activities were evaluated on human cells. The Fc units were attached to protected au residues through different Linkers using amide coupling and/or ``dick{''} reactions. Cyclic voLtammetry and UV-vis measurements showed that the triazole group conjugated to the Fc donates electrons to the ferrous center, which facilitates the oxidation of Fc that is responsible for the antiproliferative activity. These results were confirmed by the higher activity of foLate ry-triazoLeFc 21, with IC50 values at 25.4 p.M (3.2) on HeLa and 21.7 p.M (0.3) on MCF-7 cells. This compound was up to 4 -fold Less toxic to healthy PNT2 ceLLs and Fra-negative PC -3 cancer cells. Blocking experiments with an excess of free folic acid inhibited the foLate activity suggesting their specific uptake via Fra. au residue analogs of foLates, but Lacking the pteroyE moiety, were much Less toxic to cancer ceLLs than foLates. Hence, foLate ry-Fcs are potentiaL anticancer drug candidates due to their selectivity and enhanced cytotoxicity against Fra-positive maLignant cells. (AU)

FAPESP's process: 18/02093-0 - Development of new nanomaterials for nanomedicine applications
Grantee:Cátia Cristina Capêlo Ornelas Megiatto
Support Opportunities: Regular Research Grants
FAPESP's process: 15/04929-0 - Development of biosensors for instantaneous detection of proteins and cancer cells, for application on on-site biopsy
Grantee:Diego Luan Bertuzzi
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 17/06146-8 - Development of nanocarriers based on dendrimers and polymer nanoparticles for selective delivery of goniothalamin, piplartine and Monastrol
Grantee:Carolyne Brustolin Braga
Support Opportunities: Scholarships in Brazil - Post-Doctoral