Dinuclear Cu-I complexes of pyridyl-diazadiphosphetidines and aminobis(phosphonite) ligands: synthesis, structural studies and antiproliferative activity towards human cervical, colon carcinoma and breast cancer cells
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Title |
Dinuclear Cu-I complexes of pyridyl-diazadiphosphetidines and aminobis(phosphonite) ligands: synthesis, structural studies and antiproliferative activity towards human cervical, colon carcinoma and breast cancer cells
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Creator |
RASHID, A
ANANTHNAG, GS NAIK, S MAGUE, JT PANDA, D BALAKRISHNA, MS |
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Subject |
HETEROCYCLIC CARBENE COMPLEXES
COPPER(I) COMPLEXES ANTITUMOR-ACTIVITY METAL-COMPLEXES ANTICANCER AGENTS ANTIINFLAMMATORY DRUGS KINETIC STABILIZATION MICROTUBULE DYNAMICS BIOLOGICAL-ACTIVITY CHEMICAL NUCLEASE |
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Description |
The copper(I) complexes containing phosphorus donor ligands such as diazadiphosphetidine, cis-{(o-OCH2C5H4N)P(mu-(NBu)-Bu-t)}(2) (1) and aminobis(phosphonite), C6H5N{P(OC6H3(OMe-o)(C3H5-p))(2)}(2) (2, PNP), have been synthesized. Treatment of 1 with copper iodide afforded the 1D coordination polymer [{Cu(mu-I)}(2){(o-OCH2C5H4N)P(mu-(NBu)-Bu-t)}(2)](n) (3). Treatment of 3 with 2,2'-bipyridine (bpy) and 1,10-phen-anthroline (phen) produced mixed-ligand complexes [(L)(2)Cu-2{(o-OCH2C5H4N)P(mu-(NBu)-Bu-t)}(2)][I](2) (4 L = bpy; 5 L = phen) in good yields. The reaction of 2 with copper iodide yielded a rare tetranuclear copper complex [(CuI)(2)C6H5N(PR2)(2)](2) (6), which on subsequent treatment with various pyridyl ligands produced binuclear complexes [{Cu(mu-I)(py)}(2)(mu-PNP)] (7), [Cu-2(mu-I)(bpy)(2)(mu-PNP)]I (8), [Cu-2(mu-I)I(bpy)(mu-PNP)] (9), [Cu-2(phen)(bpy)(mu-PNP)](OTf)(2) (10), [Cu-2(mu-I)I(phen)(mu-PNP)] (11) and [Cu-2(mu-I(phen)(2)(mu-PNP)]I (12), in an almost quantitative yield. The new copper(I) complexes (4, 5 and 7-12) were tested for anti-cancer activity against three human tumor cell lines. Compounds 5, 10 and 12 showed in vitro antitumor activity 5-7 fold higher than cisplatin, the most used anticancer drug. These three most potent compounds (5, 10 and 12) were chosen for detailed study to understand their mechanism of action. The copper(I) compounds studied in the present investigation were found to inhibit tumor cell growth by arresting cells at the S-phase of the cell cycle. The characteristic nuclear morphology of treated cells showed signs of DNA damage. The experimental evidence clearly indicated that these compounds initiated apoptosis, which is mediated through the p53 pathway.
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Publisher |
ROYAL SOC CHEMISTRY
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Date |
2014-12-28T12:19:16Z
2014-12-28T12:19:16Z 2014 |
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Type |
Article
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Identifier |
DALTON TRANSACTIONS, 43(29)11339-11351
1477-9226 1477-9234 http://dx.doi.org/10.1039/c4dt00832d http://dspace.library.iitb.ac.in/jspui/handle/100/16488 |
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Language |
English
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