Abstract
As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential anticancer agents, complexes [AuIIIX2(dtc-Sar-l-Ser(t-Bu)- O(t-Bu))] (X = Br (1a)/Cl (1b)), [AuIIIX2(dtc-AA-Aib 2-O(t-Bu))] (AA = Sar (sarcosine, N-methylglycine), X = Br (2a)/Cl (2b); AA = d,l-Pro, X = Br (3a)/Cl (3b)), [AuIIIX2(dtc- Sar-Aib3-O(t-Bu))] (X = Br (4a)/Cl (4b)), and [AuIIIX 2(dtc-Sar-Aib3-Gly-OEt)] (X = Br (5a)/Cl (5b)) (Aib = alpha-aminoisobutyric acid, 2-methylalanine) were designed to obtain metal-based peptidomimetics that may specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several human tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy. According to in vitro cytotoxicity studies, complex [Au IIICl2(dtc-d,l-Pro-Aib2-O(t-Bu))] (3b) turned out to be the most effective toward the four human tumor cell lines evaluated (PC3, 2008, C13, and L540), for which the IC50 values were lower than cisplatin. Remarkably, it showed no cross-resistance with cisplatin itself and was proved to inhibit tumor cell proliferation by inducing almost exclusively late apoptosis/necrosis. Biological results are here reported and discussed in terms of the structure-activity relationship.
| Original language | English |
|---|---|
| Pages (from-to) | 248-260 |
| Number of pages | 13 |
| Journal | Journal of Inorganic Biochemistry |
| Volume | 117 |
| DOIs | |
| Publication status | Published - Dec 2012 |
Fingerprint
Keywords
- Anticancer activity
- Dithiocarbamates
- Drug delivery
- Gold
- Peptide transporters (PEPTs)
- Peptidomimetics
ASJC Scopus subject areas
- Biochemistry
- Inorganic Chemistry
Cite this
Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted anticancer chemotherapy. / Kouodom, Morelle Negom; Boscutti, Giulia; Celegato, Marta; Crisma, Marco; Sitran, Sergio; Aldinucci, Donatella; Formaggio, Fernando; Ronconi, Luca; Fregona, Dolores.
In: Journal of Inorganic Biochemistry, Vol. 117, 12.2012, p. 248-260.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rational design of gold(III)-dithiocarbamato peptidomimetics for the targeted anticancer chemotherapy
AU - Kouodom, Morelle Negom
AU - Boscutti, Giulia
AU - Celegato, Marta
AU - Crisma, Marco
AU - Sitran, Sergio
AU - Aldinucci, Donatella
AU - Formaggio, Fernando
AU - Ronconi, Luca
AU - Fregona, Dolores
PY - 2012/12
Y1 - 2012/12
N2 - As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential anticancer agents, complexes [AuIIIX2(dtc-Sar-l-Ser(t-Bu)- O(t-Bu))] (X = Br (1a)/Cl (1b)), [AuIIIX2(dtc-AA-Aib 2-O(t-Bu))] (AA = Sar (sarcosine, N-methylglycine), X = Br (2a)/Cl (2b); AA = d,l-Pro, X = Br (3a)/Cl (3b)), [AuIIIX2(dtc- Sar-Aib3-O(t-Bu))] (X = Br (4a)/Cl (4b)), and [AuIIIX 2(dtc-Sar-Aib3-Gly-OEt)] (X = Br (5a)/Cl (5b)) (Aib = alpha-aminoisobutyric acid, 2-methylalanine) were designed to obtain metal-based peptidomimetics that may specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several human tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy. According to in vitro cytotoxicity studies, complex [Au IIICl2(dtc-d,l-Pro-Aib2-O(t-Bu))] (3b) turned out to be the most effective toward the four human tumor cell lines evaluated (PC3, 2008, C13, and L540), for which the IC50 values were lower than cisplatin. Remarkably, it showed no cross-resistance with cisplatin itself and was proved to inhibit tumor cell proliferation by inducing almost exclusively late apoptosis/necrosis. Biological results are here reported and discussed in terms of the structure-activity relationship.
AB - As a further extension of our research work focusing on the development of gold(III)-dithiocarbamato dtc derivatives of oligopeptides as potential anticancer agents, complexes [AuIIIX2(dtc-Sar-l-Ser(t-Bu)- O(t-Bu))] (X = Br (1a)/Cl (1b)), [AuIIIX2(dtc-AA-Aib 2-O(t-Bu))] (AA = Sar (sarcosine, N-methylglycine), X = Br (2a)/Cl (2b); AA = d,l-Pro, X = Br (3a)/Cl (3b)), [AuIIIX2(dtc- Sar-Aib3-O(t-Bu))] (X = Br (4a)/Cl (4b)), and [AuIIIX 2(dtc-Sar-Aib3-Gly-OEt)] (X = Br (5a)/Cl (5b)) (Aib = alpha-aminoisobutyric acid, 2-methylalanine) were designed to obtain metal-based peptidomimetics that may specifically target two peptide transporters (namely, PEPT1 and PEPT2) upregulated in several human tumor cells. All the compounds were characterized by means of FT-IR and mono- and multidimensional NMR spectroscopy. According to in vitro cytotoxicity studies, complex [Au IIICl2(dtc-d,l-Pro-Aib2-O(t-Bu))] (3b) turned out to be the most effective toward the four human tumor cell lines evaluated (PC3, 2008, C13, and L540), for which the IC50 values were lower than cisplatin. Remarkably, it showed no cross-resistance with cisplatin itself and was proved to inhibit tumor cell proliferation by inducing almost exclusively late apoptosis/necrosis. Biological results are here reported and discussed in terms of the structure-activity relationship.
KW - Anticancer activity
KW - Dithiocarbamates
KW - Drug delivery
KW - Gold
KW - Peptide transporters (PEPTs)
KW - Peptidomimetics
UR - http://www.scopus.com/inward/record.url?scp=84869095001&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869095001&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2012.07.001
DO - 10.1016/j.jinorgbio.2012.07.001
M3 - Article
C2 - 22877925
AN - SCOPUS:84869095001
VL - 117
SP - 248
EP - 260
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
ER -