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Syntheses, Cytotoxicity and Properties of CO Releasing Molecules Containing Acetyl Salicylamide-3-pyridine 被引量:2

Syntheses, Cytotoxicity and Properties of CO Releasing Molecules Containing Acetyl Salicylamide-3-pyridine
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摘要 A series of CO-releasing molecules [M(CO)5L] (M=Cr, W, Mo, L=acetyl salicylamide 3-pyridine, 1--3; L= N,N-dimethyl-4-pyridine, 4-6; L=nicotinamide, 7--9; L=4-CHO-pyridine, 10--12) were synthesized. And in this paper, we have investigated mainly cytotoxicity and properties of the CO-releasing molecules containing acetyl salicyamide-3-pyridine, namely complexes 1--3. The stability of complexes 1 and 2 was evaluated by means of UV-Vis spectroscopy and 1H NMR spectra. The results indicate complexes 1 and 2 were stable in methanol and acidic aqueous solution, but unstable and decayed in basic media (pH 10.0). Among all the complexes, complex 2 was the slowest CO-releaser, and its half-life was 73.8 min. Complex 9 containing nicotinamide was the fastest CO-releaser with half-life only 6.5 min. In addition, cytotoxic effects of all the complexes on the proliferation of fibroblast line were assayed by MTT. Among all the complexes, the IC50 of complex 1 was 6 μmol/L, revealing complex 1 possessed stronger antiproliferative activity than the control. Analysis by Flow cytometry revealed that complex 1 arrested Hela cells in S phase while complexes 2 and 8 arrested in G2/M phase. Cell apoptosis caused by the complexes mainly occurred in "Late apoptosis". A series of CO-releasing molecules [M(CO)5L] (M=Cr, W, Mo, L=acetyl salicylamide 3-pyridine, 1--3; L= N,N-dimethyl-4-pyridine, 4-6; L=nicotinamide, 7--9; L=4-CHO-pyridine, 10--12) were synthesized. And in this paper, we have investigated mainly cytotoxicity and properties of the CO-releasing molecules containing acetyl salicyamide-3-pyridine, namely complexes 1--3. The stability of complexes 1 and 2 was evaluated by means of UV-Vis spectroscopy and 1H NMR spectra. The results indicate complexes 1 and 2 were stable in methanol and acidic aqueous solution, but unstable and decayed in basic media (pH 10.0). Among all the complexes, complex 2 was the slowest CO-releaser, and its half-life was 73.8 min. Complex 9 containing nicotinamide was the fastest CO-releaser with half-life only 6.5 min. In addition, cytotoxic effects of all the complexes on the proliferation of fibroblast line were assayed by MTT. Among all the complexes, the IC50 of complex 1 was 6 μmol/L, revealing complex 1 possessed stronger antiproliferative activity than the control. Analysis by Flow cytometry revealed that complex 1 arrested Hela cells in S phase while complexes 2 and 8 arrested in G2/M phase. Cell apoptosis caused by the complexes mainly occurred in "Late apoptosis".
出处 《Chinese Journal of Chemistry》 SCIE CAS CSCD 2015年第7期739-748,共10页 中国化学(英文版)
基金 This work was supported by the National Natural Science Foundations of China (No. 21171079) and Science Development Project of Lanzhou (No. 2014-2-34).
关键词 CO-releasing molecules PRODRUG toxicity apoptosis CO-releasing molecules, prodrug, toxicity, apoptosis
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