A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness

• Published in: European journal of medicinal chemistry Vol. 87; pp. 745 - 758
• Main Authors: Barcelos, Rosimeire Coura, Pelizzaro-Rocha, Karin Juliane, Pastre, Julio Cezar, Dias, Marina Pereira, Ferreira-Halder, Carmen Veríssima, Pilli, Ronaldo Aloise
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 24.11.2014; Elsevier
• Subjects: Acylation; Animals; AXL kinase; Aza Compounds - chemistry; Cell Line; Chemistry, Medicinal; Down-Regulation - drug effects; Goniothalamin; HIF-1α; Life Sciences & Biomedicine; N-acylated aza-derivatives; Panc-1 cells; Pancreatic cancer; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pharmacology & Pharmacy; Pyrones - chemistry; Pyrones - pharmacology; Science & Technology; Signal Transduction - drug effects; HIF-1α; MTT; Panc-1 cells; BCL-2; DMEM; FSB; GSH; Goniothalamin; BCL-xl; VEGF; STAT3; PARP-1; AXL kinase; RB; Mcl-1; ERK1/2; CDK6; AXL; CDK4; PMSF; Pancreatic cancer; ROS; N-acylated aza-derivatives; BAX; IAP; GAS6; GAPDH; HF; INDUCED CELL-DEATH; APOPTOSIS; STYRYL-LACTONE GONIOTHALAMIN; HIF-1 alpha; INDUCIBLE FACTOR-I; C-MYC; HYPOXIA; CYTOTOXIC ACTIVITY; HALOENOL LACTONE; SESQUITERPENE LACTONES; IN-VITRO EVALUATION

In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colon...