Journal
JOURNAL OF COORDINATION CHEMISTRY
Volume 66, Issue 18, Pages 3211-3228Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1080/00958972.2013.831406
Keywords
Ag(I)-N-heterocyclic carbene; Anticancer; K562; Crystal structure; Ag-Ag separation; SAR; Acute oral toxicity
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Funding
- Universiti Sains Malaysia (USM) [1001/PKIMIA/811217, 1001/PKIMIA/823082]
- (IPS) USM [RU(1001/441/CIPS/AUPE001), USM.IPS/JWT/1/19 (JLD 6): P-KD0030/11(R)]
- PRGS grant [1001/PKIMIA/834080]
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The synthesis, spectral (FT-IR and NMR), and structural studies of 1,1-methylene linked 3,3-2-cyanobenzyl bis-imidazolium salt (L-1) and respective dinuclear Ag(I)-NHC complex (C-1) are reported. The structures of both compounds were established through single-crystal X-ray diffraction. C-1 has a short Ag-Ag separation of 3.16 angstrom. Both L-1 and C-1 were tested for potential against leukemia (k562) cell line. For comparison, para-xylyl linked bis-benzimidazolium salts (L-2-L-4) and their dinuclear Ag(I)-NHC complexes (C-2-C-4) were synthesized and tested against the same cell line (K562). The IC50 values proved that L-2-L-4 and C-2-C-4 are many fold more active than L-1 and C-1. The mechanism of action and structure activity relationship are discussed. In vivo oral acute toxicity study (sighting study) was carried out which depicts that 2000mg/kg dose of selected compounds is an appropriate and safe dose for conducting main study on animals.
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