A series of new platinum(Il) bis-amidine derivatives were prepared by addition of primary and secondary aliphatic amines to coordinated nitrile ligands in cis- and trans-[PtCl2(NCR)2] (R = Me, Ph, CH2Ph). The bis-amidine complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicated that the trans isomers are more effective than the cis species, and in particular the benzamidine complex trans-[PtCl2{E-N(H)=C(NMe2)Ph}2] was the most active derivative and was able to circumvent acquired cisplatin resistance, thus suggesting a different mechanism of action compared to that exhibited by cisplatin. New benzyliminoether derivatives cis- and trans-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] were also prepared by addition of MeOH to cis- and trans-[PtCl2(NCCH2Ph)2] and the cytotoxic properties were evaluated in terms of cell growth inhibition against a panel of different types of human cancer cell lines. The complex cis-[PtCI2{E-N(H)=C(OMe)CH2Ph}2] was significantly more potent than cisplatin against all tumour cell lines, including cisplatin-resistant ones. Moreover, the in vivo studies, performed on two transplantable tumour models, showed that cis-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] exhibited a marked activity against murine L1210 leukaemia and Lewis lung carcinoma in terms of survival prolongation and tumour growth inhibition, respectively.

Synthesis of cisplatin analogues: cytitoxic efficacy and anti-tumor activity of bis-amidine and bis-iminoether Pt(II) complexes

BERTANI, ROBERTA;GANDIN, VALENTINA;MICHELIN, RINO;MARZANO, CRISTINA
2009

Abstract

A series of new platinum(Il) bis-amidine derivatives were prepared by addition of primary and secondary aliphatic amines to coordinated nitrile ligands in cis- and trans-[PtCl2(NCR)2] (R = Me, Ph, CH2Ph). The bis-amidine complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicated that the trans isomers are more effective than the cis species, and in particular the benzamidine complex trans-[PtCl2{E-N(H)=C(NMe2)Ph}2] was the most active derivative and was able to circumvent acquired cisplatin resistance, thus suggesting a different mechanism of action compared to that exhibited by cisplatin. New benzyliminoether derivatives cis- and trans-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] were also prepared by addition of MeOH to cis- and trans-[PtCl2(NCCH2Ph)2] and the cytotoxic properties were evaluated in terms of cell growth inhibition against a panel of different types of human cancer cell lines. The complex cis-[PtCI2{E-N(H)=C(OMe)CH2Ph}2] was significantly more potent than cisplatin against all tumour cell lines, including cisplatin-resistant ones. Moreover, the in vivo studies, performed on two transplantable tumour models, showed that cis-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] exhibited a marked activity against murine L1210 leukaemia and Lewis lung carcinoma in terms of survival prolongation and tumour growth inhibition, respectively.
2009
platinum and other heavy metal compounds in cancer chemotherapy
9781603274586
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/2515766
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