Synthesis and properties of (diamine)platinum(II) complexes of pyridine carboxylate isomers and their antitumor activity

Abstract

Novel (diamine)platinum(II) complexes of the isomeric pyridine carboxylate ligands [A(2)Pt(PyCA)(x)](PyCA)(2-x) (A(2) = 2,2'-dimethyl-1,3-propanediamine (dmpda), trans-(+/-)-1,2-diaminocyclohexane (dach), ethylenediamine (en), PyCA = picolinate (pic), nicotinate (nic), and isonicotinate (isonic), x = 1 or 2) have been prepared from the reaction of (diamine)Pt(SO,) and Ba[PyCA], in aqueous solution. All products were obtained as crystals. Different coordination modes were observed depending on the position of the carboxylate group on the pyridine ring. Picolinate with the carboxylate group in the ortho-position chelated the platinum(II) atom by a (N,O) chelation mode resulting in the formation of a cationic complex. However, nicotinate and isonicotinate with the carboxylate group in meta- and pala-positions, respectively, did not chelate but coordinated to the platinum(II) atom through their nitrogen atoms resulting in the formation of zwitterionic complexes. [(dmpda)Pt(pic)](+) (pic)(-) crystallizes in the monoclinic system, space group P2(1)/c (No. 14) with a = 9.586(4), b = 10.797(2), c = 18.460(4) Angstrom; beta = 100.267(2)degrees, V = 1880.1(9) Angstrom(3) and Z = 4, and (dmpda)Pt(isonic), crystallizes in the triclinic system, space group P (1) over bar (No. 2) with a = 8.721(14), b = 10.981(3), c = 15.093(3) Angstrom; alpha = 80.10(2), beta = 74.48(14), gamma = 70.2(18)degrees; V = 1305.9(5) Angstrom(3) and Z = 2. Some of these compounds exhibit a significant antitumor activity in vitro against mouse leukemia cell line, which is comparable to that of carboplatin. (C) 1999 Elsevier Science S.A. All rights reserved.