Diorganotin(IV) N-acetyl-L-cysteinate complexes: synthesis, solid state, solution phase, DFT and biological investigations.
Diorganotin(IV) complexes of N-acetyl-L-cysteine (H(2)NAC; (R)-2-acetamido-3-sulfanylpropanoic acid) have been synthesized and their solid and solution-phase structural configurations investigated by FTIR, Mössbauer, (1)H, (13)C and (119)Sn NMR spectroscopy. FTIR results suggested that in R(2)Sn(IV)NAC (R = Me, Bu, Ph) complexes NAC(2-) behaves as dianionic tridentate ligand coordinating the tin(IV) atom, through ester-type carboxylate, acetate carbonyl oxygen atom and the deprotonated thiolate group. From (119)Sn Mössbauer spectroscopy it could be inferred that the tin atom is pentacoordinated, with equatorial R(2)Sn(IV) trigonal bipyramidal configuration. In DMSO-d(6) solution, NMR spectroscopic data showed the coordination of one solvent molecule to tin atom, while the coordination mode of the ligand through the ester-type carboxylate and the deprotonated thiolate group was retained in solution. DFT (Density Functional Theory) study confirmed the proposed structures in solution phase as well as the determination of the most probable stable ring conformation. Biological investigations showed that Bu(2)SnCl(2) and NAC2 induce loss of viability in HCC cells and only moderate effects in non-tumor Chang liver cells. NAC2 showed lower cytotoxic activity than Bu(2)SnCl(2), suggesting that the binding with NAC(2-) modulates the marked cytotoxic activity exerted by Bu(2)SnCl(2). Therefore, these novel butyl derivatives could represent a new class of anticancer drugs.
Pellerito
Lorenzo
L
Dipartimento di Chimica Inorganica e Analitica Stanislao Cannizzaro, Università degli Studi di Palermo, Viale delle Scienze, Ed. 17-90128 Palermo, Italy. bioinorg@unipa.it
Prinzivalli
Cristina
C
Casella
Girolamo
G
Fiore
Tiziana
T
Pellerito
Ornella
O
Giuliano
Michela
M
Scopelliti
Michelangelo
M
Pellerito
Claudia
C
D000111:Acetylcysteine / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D006801:Humans; D015394:Molecular Structure; D009947:Organotin Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013057:Spectrum Analysis
D000970:Antineoplastic Agents; D009947:Organotin Compounds; D000111:Acetylcysteine