A novel silver iodide metalo-drug: Experimental and computational modelling assessment of its interaction with intracellular DNA, lipoxygenase and glutathione
PBN-AR
Instytucja
Wydział Chemii (Uniwersytet im. Adama Mickiewicza w Poznaniu)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
European Journal of Medicinal Chemistry
ISSN
0223-5234
EISSN
Wydawca
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI
URL
Rok publikacji
2014
Numer zeszytu
Strony od-do
388-399
Numer tomu
77
Identyfikator DOI
Liczba arkuszy
Autorzy
(liczba autorów: 6)
Pozostali autorzy
+ 5
Streszczenia
Język
en
Treść
The new mixed ligand silver(I) complex of formula [AgI(TPP)(2)(MBZT)] (1) was obtained by reacting 2-mercapto-benzothiazole (MBZT) with triphenylphosphine (TPP). The complex was characterized by m.p., vibrational spectroscopy (FT-IR), H-1 NMR, UV-vis, ESI-MS spectroscopic techniques and its structure was confirmed by X-ray crystallography. Mixed ligand complexes of silver(l) iodide with thiones and phosphines are very rare in the literature and to the best of our knowledge compound 1 is the first of this kind exhibiting significant biological effects. Complex 1 was evaluated for its in vitro cytotoxic activity (cell viability) under irradiation with UV light and without irradiation against human cancer cell lines: MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), Caki-1 (renal), A549 (lung), OAW-42 (ovarian), HeLa (cervical) and additionally against the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line (MTSV17) with SRB assay. The results showed that 1 mediates a strong cytotoxic response to the tested normal and cancer cell lines. It exhibits equal activity against MDA-MB-231 cells where estrogen receptors (ERs) are devoid with the one against MCF-7 where ERs are present. Molecular docking studies have shown that 1 is docked in the different pocket than that of the ERs modulators. The binding affinity of 1 towards the intracellular molecules DNA and lipoxygenase (LOX) was studied for the evaluation of the mechanism of its cytostasis. The binding constant (K-b) of 1 towards CT-DNA was calculated by UV Vis and fluorescent spectra suggesting intercalation or electrostatic interactions of 1 into DNA. Docking studies on DNA-complex interactions confirm the binding of I. Moreover, the influence of complex I on the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. In addition, since the deactivation of cisplatin caused by glutathione, seems to be an important determinant of its cytotoxic effects, the reaction of 1 with glutathione (GSH) was investigated by UV-absorption spectroscopy. (C) 2014 Elsevier Masson SAS. All rights reserved.
Cechy publikacji
discipline:Biochemia – dziedzina nauk chemicznych
discipline:Chemia
discipline:Technologia chemiczna – dziedzina nauk chemicznych
discipline:Biochemistry – field of chemical sciences
discipline:Chemistry
discipline:Chemical Technology – field of chemical sciences
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:763902
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