.png){kind=icon}
.png){kind=icon}
Return
Design, synthesis, and evaluation of novel C6-substituted purine-isoxazole derivatives and their Re(I) tricarbonyl complexes: antiproliferative activity and integrated in silico study
.png){kind=icon}
PRE
AI
B
S
A
S
S
P
D
B
K
R
DOI：10.1016/j.molstruc.2026.146076.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Herein, we report the design and synthesis of C6-substituted purine and 7-deazapurine isoxazole derivatives via 1,3-dipolar cycloaddition, followed by microwave-assisted Suzuki-Miyaura and Sonogashira cross-coupling reactions. Selected pyridine-isoxazole ligands were coordinated to fac-[Re(CO)5Cl], and the resulting Re(I) tricarbonyl complexes were characterized by UV-Vis, IR, NMR spectroscopy, and elemental analysis. The structure of complex 8aRe was confirmed by single-crystal X-ray diffraction analysis, revealing facial coordination of the carbonyl ligands and distorted octahedral geometry around the rhenium center. Antiproliferative activity of all compounds was evaluated across eight human cancer cell lines. Structure-activity relationship analysis demonstrated that arylalkynyl substitution at the C-6 position of purine and 7-deazapurine scaffolds significantly enhances antiproliferative potency, whereas directly arylated derivatives were largely inactive. Among the ligands, compound 6b emerged as the most potent, displaying low-micromolar IC50 values against pancreatic cancer Capan-1, T-cell leukemia DND-41, acute myeloid leukemia HL-60, and non-Hodgkin lymphoma Z-138 cell lines (IC50 = 1.5-2.1 mu M). Although these potencies are promising, selectivity toward nonmalignant cells remained moderate (SI = 3.7-4.8), indicating that further optimization is required. Rhenium coordination further increased antiproliferative activity but also reduced selectivity, with complex 8bRe showing consistent low-micromolar potency across the same cell lines (IC50 = 1.6-1.9 mu M, SI = 1.5-1.8). Molecular docking and in silico ADME analyses indicated favorable drug-like properties and suggested the STAT3 SH2 domain as a possible molecular target for both 6b and 8bRe, supporting their potential as promising lead compounds for selectivity improvement and further anticancer development.
Keywords:
Purine
7-deazapurine
Isoxazole
Rhenium(I) tricarbonyl complexes
Antiproliferative activity
Molecular docking
Journal
IF:
4.7
Papers:
3.5W
Citations:
6.6W
Organization
Cited Papers