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Copper (II) complexes of substituted salicylaldehyde dibenzyl semicarbazones: Synthesis, cytotoxicity and interaction with quadruplex DNA
Citation
Siti Munira Haidad Ali, Yan, Y.-K., Lee, P. P. F., Khong, K. Z. X., Mahasin Alam Sk, Lim, K. H., Klejevskaja, B., & Vilar, R. (2014). Copper (II) complexes of substituted salicylaldehyde dibenzyl semicarbazones: Synthesis, cytotoxicity and interaction with quadruplex DNA. Dalton Transactions, 43(3), 1449-1459. https://doi.org/10.1039/C3DT52297K
Author
Siti Munira Haidad Ali
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Khong, Kenny Zhi Xiang
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Mahasin Alam Sk
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Lim, Kok Hwa
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Klejevskaja, Beata
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Vilar, Ramon
Abstract
A series of substituted salicylaldehyde dibenzyl semicarbazones [RC6H3(OH)CH=NNHCON(CH2Ph)2] and their copper(II) complexes were synthesized and characterized. The chloridocopper(II) complexes of the 4- OH and 5-OH substituted ligands (complexes 9 and 7) show modest affinity and good selectivity (over duplex DNA) for the quadruplex formed from the 22AG human telomeric (HTelo) DNA sequence. Substitution of the chlorido ligands of these two complexes with pyridine yielded derivatives (7-py and 9-py) with increased affinity for HTelo. These derivatives also show good selectivity for HTelo over calf-thymus DNA (170- and 211-fold, respectively). The X-ray crystal structures of 9 and 9-py were determined. Molecular docking studies based on these structures show that the complexes stack on the 5′-end of the HTelo quadruplex, with the hydroxyl group forming a hydrogen bond with a guanine residue. Complexes 7, 9, 7-py and 9-py display significant cytotoxicity against MOLT-4 human leukaemia cells. Interestingly, they have low to negligible cytotoxicity against the non- cancerous IMR-90 human fibroblasts.
Date Issued
2009
Publisher
Royal Society of Chemistry
Journal
Dalton Transactions