Effect of lipophilicity of amylamine and amylglycine ligands on biological activity of new anticancer cisplatin analog.
Investigation of side effects and solubility of anticancer drugs is a major challenge in chemotherapy science. Thus, design and synthesis of cisplatin analogs with higher lipophilicity as novel water-soluble anticancer drugs is valuable. In this work, two new Pt(II) complexes were synthesized with formula cis-[Pt(NH3)2(amylgly)]NO3and cis-[Pt(amylamine)2(amylgly)]NO3, where gly is penthyl glycine as an amino acid. The new compounds were synthesized and extensively characterized using analytical techniques; spectroscopic methods, and conductivity measurement. The anticancer activity of synthesized complexes was investigated against colon cancer cell line HCT116 using MTT assay and results showed excellent anticancer activity with Cc50values of 36 and 270 M after 24-h incubation time for cis-[Pt(NH3)2(amylgly)]NO3and cis-[Pt(NH2-amyl)2(amylgly)]NO3, respectively; which is lower than that for cisplatin. These complexes were also interacted with highly polymerized calf thymus DNA and the binding mode of the complexes to CT-DNA was evaluated by fluorescence, circular dichroism, and UV spectroscopy. The calculation of binding and thermodynamic of Pt(II) complexes with CT-DNA can provide deeper insight into mechanism of the action of these types of complexes with nucleic acids. So, thermodynamic parameters were also determined according to isothermal titration. In comparison with cis-[Pt(NH3)2(amylgly)]NO3in DNA interaction, the result show that cis-[Pt(NH2-amyl)2(amylgly)]NO3has higher affinity with binding constant Kf= 8.72 mM to CT-DNA. The results indicate that cis-[Pt(amylamine)2(amylgly)]NO3with large and bulky aliphatic group bind to CT-DNA by different modes and covalent and groove bindings were preferred mode of interaction with DNA.
a Department of Chemistry, Science and Research Branch , Islamic Azad University , Tehran , Iran.
Fatemeh
F
Safa Shams Abyaneh
b Chemistry & Chemical Engineering Research Center of Iran , Tehran , Iran.
Mahboube
M
Eslami Moghadam
a Department of Chemistry, Science and Research Branch , Islamic Azad University , Tehran , Iran.
Moayad
M
Hossaini Sadr
c Department of Cell & Molecular Sciences, Faculty of Biological Sciences , Kharazmi University , Tehran , Iran.
Adeleh
A
Divsalar
D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002942:Circular Dichroism; D002945:Cisplatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000187:drug effects; D005998:Glycine / Q000138:chemical synthesis / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy; D013816:Thermodynamics
D000588:Amines; D000970:Antineoplastic Agents; D008024:Ligands; D004247:DNA; C427203:calf thymus DNA; C005264:n-amylamine; D002945:Cisplatin; D005998:Glycine
Cisplatin analog; amylglycine, DNA interaction; anticancer drug; cytotoxicity