title: Biophysical studies on the effect of the 13 position substitution of the anticancer alkaloid berberine on its DNA binding.
abstract: The structural effects and thermodynamics of the DNA binding of six berberine analogues with alkyl chains of varying length and a terminal phenyl group at the C-13 position were investigated. All the analogues bound DNA noncooperatively in contrast to the cooperative binding of berberine. The binding affinity was higher and the effect of the chain length was only up to (CH(2))(3), after which the binding affinity decreased slightly. Intercalative binding with strong stabilization of the DNA helix was revealed. Binding resulted in the weakening of the base stacking with moderate conformational changes within the B-form. The binding was entropy driven in each case, the entropy contribution to the free energy increasing with the chain length up to the threshold (CH(2))(3). The complexation was dominated by nonpolyelectrolytic forces in each case; polyelectrolytic forces contributed only a quarter to the total free energy at 50 mM [Na(+)]. Overall, the phenylalkyl substitution at the C-13 position considerably enhanced the DNA binding and was highest for the analogue with (CH(2))(3). Structural and thermodynamic data on the DNA binding aspects of the substituted berberines are presented in comparison with berberine.
authors.affiliation: Biophysical Chemistry Laboratory, Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India.
authors.forename: Debipreeta
authors.initials: D
authors.lastname: Bhowmik
authors.forename: Maidul
authors.initials: M
authors.lastname: Hossain
authors.forename: Franco
authors.initials: F
authors.lastname: Buzzetti
authors.forename: Rosaria
authors.initials: R
authors.lastname: D'Auria
authors.forename: Paolo
authors.initials: P
authors.lastname: Lombardi
authors.forename: Gopinatha Suresh
authors.initials: GS
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001665:Binding Sites; D002152:Calorimetry, Differential Scanning; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D013816:Thermodynamics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001599:Berberine; D004247:DNA; C427203:calf thymus DNA