Synthesis and anticancer evaluations of novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative for the treatment of colorectal cancer

Hu, Shujian; Ma, Wantong; Wang, Junyi; Ma, Yunhao; Zhou, Zhaoyang; Zhang, Rentao; Du, Kangjia; Zhang, Hao; Sun, Mengze; Jiang, Xinrong; Tu, Hongyuan; Tang, Xiaoliang; Yao, Xiaojun; Chen, Peng

doi:10.1016/j.ejphar.2022.175120

Cited by 8 publications

(2 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ligand L was synthesized according to the method previously reported by us. 43 Briefly, 1,10-phenanthroline-5,6-dione (1.05 g, 5.0 mmol), 4-hydroxybenzaldehyde (0.61 g, 5.0 mmol), and ammonium acetate (3.85 g, 50 mmol) were dissolved in glacial acetic acid (60 mL). The mixture was refluxed for 24 h under an inert atmosphere of argon.…”

Section: Synthesis Of Ligand Lmentioning

confidence: 99%

Lysosome-targeted cyclometalated Ir(iii) complexes as photosensitizers/photoredox catalysts for cancer therapy

Chen,

Liang,

Kou

et al. 2024

Dalton Trans.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Synthesis Of Ligand Lmentioning

confidence: 99%

Lysosome-targeted cyclometalated Ir(iii) complexes as photosensitizers/photoredox catalysts for cancer therapy

Chen,

Liang,

Kou

et al. 2024

Dalton Trans.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The development of anticancer agents that exhibit numerous mechanisms of action is of great importance since such compounds may have the ability to overcome typical obstacles such as ineffectiveness toward tumors and drug resistance. , A promising strategy in drug development to increase the potential of anticancer drugs in exhibiting multiple mechanisms of action is the coordination of organic molecules with anticancer potential to various metals. With this in mind and the recent success of imidazo[4,5- f ]1,10-phenanthroline derivatives as prospective anticancer agents in colorectal and liver cancer, − we designed a small library of rhenium(I) tricarbonyl complexes (Figure ) with N,N′ -bidentate imidazo[4,5- f ]1,10-phenanthroline derivative ligand systems, with systematic changes with N,S and aromatic motifs on the backbone, having an appended aqua ligand to evaluate their potentials as anticancer agents. Rhenium(I) tricarbonyl complexes are usually kinetically inert, which will help increase the complex half-life to reach the target.…”

Section: Introductionmentioning

confidence: 99%

Rhenium(I) Tricarbonyl Complexes of 1,10-Phenanthroline Derivatives with Unexpectedly High Cytotoxicity

Enslin,

Purkait,

Pozza

et al. 2023

Inorg. Chem.

View full text Add to dashboard Cite

Eight rhenium(I) tricarbonyl aqua complexes with the general formula fac-[Re(CO) 3 (N,N′-bid)(H 2 O)][NO 3 ] (1− 8), where N,N′-bid is (2,6-dimethoxypyridyl)imidazo[4,5-f ]1,10phenanthroline (L1), (indole)imidazo[4,5-f ]1,10-phenanthroline (L2), (5-methoxyindole)-imidazo[4,5-f ]1,10-phenanthroline (L3), (biphenyl)imidazo[4,5-f ]1,10-phenanthroline (L4), (fluorene)imidazo[4,5-f ]1,10-phenanthroline (L5), (benzo[b]thiophene)imidazo[4,5-f ]1,10-phenanthroline ( L6), (5-bromothiazole)imidazo[4,5-f ]1,10-phenanthroline (L7), and (4,5dimethylthiophene)imidazo[4,5-f ]1,10-phenanthroline (L8), were synthesized and characterized using 1 H and 13 C{ 1 H} NMR, FT-IR, UV/Vis absorption spectroscopy, and ESI-mass spectrometry, and their purity was confirmed by elemental analysis. The stability of the complexes in aqueous buffer solution (pH 7.4) was confirmed by UV/Vis spectroscopy. The cytotoxicity of the complexes (1− 8) was then evaluated on prostate cancer cells (PC3), showing a low nanomolar to low micromolar in vitro cytotoxicity. Worthy of note, three of the Re(I) tricarbonyl complexes showed very low (IC 50 = 30−50 nM) cytotoxic activity against PC3 cells and up to 26-fold selectivity over normal human retinal pigment epithelial-1 (RPE-1) cells. The cytotoxicity of both complexes 3 and 6 was lowered under hypoxic conditions in PC3 cells. However, the compounds were still 10 times more active than cisplatin in these conditions. Additional biological experiments were then performed on the most selective complexes (complexes 3 and 6). Cell fractioning experiments followed by ICP-MS studies revealed that 3 and 6 accumulate mostly in the mitochondria and nucleus, respectively. Despite the respective mitochondrial and nuclear localization of 3 and 6, 3 did not trigger the apoptosis pathways for cell killing, whereas 6 can trigger apoptosis but not as a major pathway. Complex 3 induced a paraptosis pathway for cell killing while 6 did not induce any of our other tested pathways, namely, necrosis, paraptosis, and autophagy. Both complexes 3 and 6 were found to be involved in mitochondrial dysfunction and downregulated the ATP production of PC3 cells. To the best of our knowledge, this report presents some of the most cytotoxic Re(I) carbonyl complexes with exceptionally low nanomolar cytotoxic activity toward prostate cancer cells, demonstrating further the future viability of utilizing rhenium in the fight against cancer.

show abstract

Recent advances on biologically active coumarin-based hybrid compounds

2023

View full text Add to dashboard Cite

Synthesis and anticancer evaluations of novel 1H-imidazole [4,5-f][1,10] phenanthroline derivative for the treatment of colorectal cancer

Cited by 8 publications

References 24 publications

Lysosome-targeted cyclometalated Ir(iii) complexes as photosensitizers/photoredox catalysts for cancer therapy

Lysosome-targeted cyclometalated Ir(iii) complexes as photosensitizers/photoredox catalysts for cancer therapy

Rhenium(I) Tricarbonyl Complexes of 1,10-Phenanthroline Derivatives with Unexpectedly High Cytotoxicity

Recent advances on biologically active coumarin-based hybrid compounds

Contact Info

Product

Resources

About