Interactions of two cytotoxic organotin(IV) compounds with calf thymus DNA.
The reactions with DNA of two antitumor active organotin(IV) compounds, the dimer of bis[(di-n-butyl 3,6-dioxaheptanoato)tin] (C(52)H(108)Sn(4)O(1) x 2H(2)O), compound 1, and tri-n-butyltin 3,6,9-trioxodecanoate (C(19)H(40)SnO(5) x 1/2H(2)O), compound 2, were analysed by circular dichroism, DNA melting experiments and gel mobility shift assays. It is found that both complexes modify only slightly the B-type circular dichroism spectroscopy (CD) spectrum of calf thymus DNA. On the other hand, both complexes were found to affect significantly the parameters of the thermally induced helix-to-coil transition. Addition of 1 or 2 to calf thymus DNA samples does not favor DNA renaturation after melting ruling out formation of interstrand crosslinks. Moreover, the effects of both compounds on plasmid DNA gel mobility were investigated. From the analysis of the present results it is inferred that both organotin(IV) compounds do interact with DNA, probably at the level of the phosphate groups.
Casini
A
A
Department of Chemistry, University of Florence, via Gino Capponi 7, 50121 Florence, Italy.
Messori
L
L
Orioli
P
P
Gielen
M
M
Kemmer
M
M
Willem
R
R
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002417:Cattle; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry / Q000187:drug effects*; D009690:Nucleic Acid Conformation; D009947:Organotin Compounds / Q000494:pharmacology*; D013950:Thymus Gland / Q000378:metabolism*
D000970:Antineoplastic Agents; D009947:Organotin Compounds; C437425:bis((di-n-butyl 3,6-dioxaheptanoato)tin); C437443:tri-n-butyltin 3,6,9-trioxodecanoate; D004247:DNA