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Interaction of antitumor drug Sn(CH3)2Cl2 with DNA and RNA |
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| Authors: | Shohreh Nafisi Amir Sobhanmanesh Majid Esm-Hosseini Kamran Alimoghaddam Heidar Ali Tajmir-Riahi |
| Affiliation: | aDepartment of Chemistry, Azad University, Tehran Central Branch, Tehran 14169 63316, Iran bDepartment of Chemistry, Urumieh University, Urumieh, Iran cHematology, Oncology and BMT research Center, Tehran University of Medical Science, Shariati Hospital, Kargar Ave., Tehran 14117 13131, Iran dDepartment of Chemistry-Biology, University of Quebec at Trois-Rivieres, C. P. 500, TR, Que., Canada G9A 5H7 |
| Abstract: | Sn(CH3)2Cl2 exerts its antitumor activity in a specific way. Unlike anticancer cis-Pt(NH3)2Cl2 drug which binds strongly to the nitrogen atoms of DNA bases, Sn(CH3)2Cl2 shows no major affinity towards base binding. Thus, the mechanism of action by which tinorganometallic compounds exert antitumor activity would be different from that of the cisplatin drug. The aim of this study was to examine the binding of Sn(CH3)2Cl2 with calf thymus DNA and yeast RNA in aqueous solutions at pH 7.1–6.6 with constant concentrations of DNA and RNA and various molar ratios of Sn(CH3)2Cl2/DNA (phosphate) and Sn(CH3)2Cl2/RNA of 1/40, 1/20, 1/10, 1/5. Fourier transform infrared (FTIR) and UV–visible difference spectroscopic methods were used to determine the Sn(CH3)2Cl2 binding mode, binding constant, sequence selectivity and structural variations of Sn(CH3)2Cl2/DNA and Sn(CH3)2Cl2/RNA complexes in aqueous solution. Sn(CH3)2Cl2 hydrolyzes in water to give Sn(CH3)2(OH)2 and [Sn(CH3)2(OH)(H2O)n]+ species. Spectroscopic evidence showed that interaction occurred mainly through (CH3)2Sn(IV) hydroxide and polynucleotide backbone phosphate group with overall binding constant of K(Sn(CH3)2Cl2–DNA)=1.47×105 M−1 and K(Sn(CH3)2Cl2–RNA)=7.33×105 M−1. Sn(CH3)2Cl2 induced no biopolymer conformational changes with DNA remaining in the B-family structure and RNA in A-conformation upon drug complexation. |
| Keywords: | DNA RNA Drug Sn cation Binding constant Conformation FTIR UV–Visible spectroscopy |
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