Activity and Selectivity of Novel Chemical Metallic Complexes with Potential Anticancer Effects on Melanoma Cells

被引:3
作者
Ciardulli, Maria Camilla [1 ]
Mariconda, Annaluisa [2 ]
Sirignano, Marco [3 ]
Lamparelli, Erwin Pavel [1 ]
Longo, Raffaele [4 ]
Scala, Pasqualina [1 ]
D'Auria, Raffaella [1 ]
Santoro, Antonietta [1 ,5 ]
Guadagno, Liberata [4 ]
Della Porta, Giovanna [1 ,5 ]
Longo, Pasquale [3 ]
机构
[1] Univ Salerno, Dept Med Surg & Dent, Via S Allende, I-84081 Baronissi, Italy
[2] Univ Basilicata, Dept Sci, Viale Ateneo Lucano 10, I-85100 Potenza, Italy
[3] Univ Salerno, Dept Chem & Biol Adolfo Zambelli, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy
[4] Univ Salerno, Dept Ind Engn, Via Giovanni Paolo II 132, I-84084 Fisciano, Italy
[5] Univ Salerno, Interdept Ctr BIONAM, Via Giovanni Paolo II, I-84084 Fisciano, Italy
来源
MOLECULES | 2023年 / 28卷 / 12期
关键词
human malignant melanoma cells; immortal keratinocyte from adult human skin; N-heterocyclic carbene complexes; metallorganic anticancer agents; toxicity; selectivity; 3D culture; live cell imaging; HETEROCYCLIC CARBENE COMPLEXES; IMPROVED SURVIVAL; CANCER; GROWTH; DRUG; INHIBITION; MECHANISMS; APOPTOSIS;
D O I
10.3390/molecules28124851
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human malignant melanoma cells from lymph node metastatic site (MeWo) were selected for testing several synthesized and purified silver(I) and gold(I) complexes stabilized by unsymmetrically substituted N-heterocyclic carbene (NHC) ligands, called L20 (N-methyl, N & PRIME;-[2-hydroxy ethylphenyl]imidazol-2-ylide) and M1 (4,5-dichloro, N-methyl, N & PRIME;-[2-hydroxy ethylphenyl]imidazol-2-ylide), having halogenide (Cl- or I-) or aminoacyl (Gly=N-(tert-Butoxycarbonyl)glycinate or Phe=(S)-N-(tert-Butoxycarbonyl)phenylalaninate) counterion. For AgL20, AuL20, AgM1 and AuM1, the Half-Maximal Inhibitory Concentration (IC50) values were measured, and all complexes seemed to reduce cell viability more effectively than Cisplatin, selected as control. The complex named AuM1 was the most active just after 8 h of treatment at 5 & mu;M, identified as effective growth inhibition concentration. AuM1 also showed a linear dose and time-dependent effect. Moreover, AuM1 and AgM1 modified the phosphorylation levels of proteins associated with DNA lesions (H2AX) and cell cycle progression (ERK). Further screening of complex aminoacyl derivatives indicated that the most powerful were those indicated with the acronyms: GlyAg, PheAg, AgL20Gly, AgM1Gly, AuM1Gly, AgL20Phe, AgM1Phe, AuM1Phe. Indeed, the presence of Boc-Glycine (Gly) and Boc-L-Phenylalanine (Phe) showed an improved efficacy of Ag main complexes, as well as that of AuM1 derivatives. Selectivity was further checked on a non-cancerous cell line, a spontaneously transformed aneuploid immortal keratinocyte from adult human skin (HaCaT). In such a case, AuM1 and PheAg complexes resulted as the most selective allowing HaCaT viability at 70 and 40%, respectively, after 48 h of treatment at 5 & mu;M. The same complexes tested on 3D MeWo static culture induced partial spheroid disaggregation after 24 h of culture, with almost half of the cells dead.
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页数:22
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