Synthesis of Nitrogen-Containing Goniothalamin Analogues with Higher Cytotoxic Activity and Selectivity against Cancer Cells

Author(s)

Meirelles, Matheus A. ^[1] ; Braga, Carolyne B. ^[1] ; Ornelas, Catia ^[1] ; Pilli, Ronaldo A. ^[1]

Affiliation

^[1] Univ Estadual Campinas, UNICAMP, Inst Chem, Dept Organ Chem, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: CHEMMEDCHEM; v. 14, n. 15 JULY 2019.
• Web of Science Citations: 0

Abstract

Two series of racemic goniothalamin analogues displaying nitrogen-containing groups were designed and synthesized. A total of 19 novel analogues were evaluated against a panel of four different cancer cell lines, along with the normal prostate cell line PNT2 to determine their selectivity. Among them, goniothalamin chloroacrylamide 13 e displayed the lowest IC50 values for both MCF-7 (0.5 mu m) and PC3 (0.3 mu m) cells, about 26-fold more potent than goniothalamin (1). Besides its higher potency, compound 13 e also displayed much higher selectivity than goniothalamin. In contrast, goniothalamin isobutyramide 13 c was the most potent analogue against Caco-2 cells (IC50=0.8 mu m), about 10-fold more potent and 17-fold more selective than 1. These results reveal the potential of compounds 13 c and 13 e for further in vivo studies, representing the first goniothalamin analogues with IC50 values in the low micromolar range and high selectivity against MCF-7, Caco-2, and PC3 cancer cell lines. (AU)

• FAPESP's process: 13/07607-8 - OCRC - Obesity and Comorbidities Research Center
• Grantee: Licio Augusto Velloso
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• 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: 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