Theoretical study of fast repair of DNA damage by cistanoside C and analogs: mechanism and docking

Experiments show that the natural substances phenylpropanoid glycosides (PPGs) extracted from pelicularis spicata are capable of repairing DNA damaged by oxygen radicals. Based on kinetic measurements and experiments on tumor cells, a theoretical study of the interaction between PPG molecules and isolated DNA bases, as well as a DNA fragment has been performed. An interaction mechanism reported early has been refined. The docking calculations performed using junction minimization of nucleic acids (JUMNA) software showed that the PPG molecules can be docked into the minor groove of DNA and form complexes with the geometry suitable for an electron transfer between guanine radical and the ligand. Such complexes can be formed without major distortions of DNA structure and are further stabilized by the interaction with the rhamnosyl side-groups.     

Docking study of cistanoside C to telomeric DNA fragment

Experiments show that the natural products phenyl propanoid glycosides (PPGs) extracted from the plant Pedicularis spicata are capable of repairing DNA damaged by oxygen radicals. Based on kinetic measurements and experiments on tumor cells, a theoretical study of the interaction between PPG molecule Cistanoside C and telomeric DNA fragment has been carried out. The docking calculations performed using JUMNA software showed that the Cistanoside C could be docked into the minor groove of telomeric DNA and form complexes with the geometry suitable for an electron transfer between guanine radical and the ligand. Such complexes can be formed without major distortions of DNA structure and are further stabilized by the interaction with the saccharide side-groups.     

Docking study of cistanoside C to telomeric DNA fragment

Experiments show that the natural products phenyl propanoid glycosides (PPGs) extracted from the plant Pedicularis spicata are capable of repairing DNA damaged by oxygen radicals. Based on kinetic measurements and experiments on tumor cells, a theoretical study of the interaction between PPG molecule Cistanoside C and telomeric DNA fragment has been carried out. The docking calculations performed using JUMNA software showed that the Cistanoside C could be docked into the minor groove of telomeric DNA and form complexes with the geometry suitable for an electron transfer between guanine radical and the ligand. Such complexes can be formed without major distortions of DNA structure and are further stabilized by the interaction with the saccharide side-groups.     

Atom-atom potential analysis of the complexing characteristics of cyclodextrins (host) with benzene and p-dihalobenzenes (guest)

Abstract

Intermolecular interaction and modelling calculations on the complexes of α-, β- and γ-cyclodextrins (host) with benzene and p-dihalobenzenes (guest) were performed. The complex formation mechanism between the host and guest molecules was evaluated from three-dimensional potential maps generated by the atom-atom potential method, and the molecular packing of the complexed compounds was visualized by a space-fill representation. Stable inclusion complexes only form when both the host and guest molecules experience a significant decrease in the complexing potential. The host and guest molecules have a maximum molecular surface contact at the minimum potential, which depends on both the cavity size and the molecular volumes of the guest molecules. The calculated interaction energies can be correlated to the association constants of complex formation determined from experiment. The molecular dynamics of the guest molecules are also discussed.     

基于取代苯甲酰肼缩丙酮酸配体的二苄基锡配合物的合成、晶体结构及生物活性

二苄基二氯化锡分别与对甲氧基苯甲酰肼缩丙酮酸及对硝基苯甲酰肼缩丙酮酸反应,合成了2个二苄基锡配合物(C1、C2),通过元素分析、IR、~1H NMR、~(13)C NMR、~(119)Sn NMR、HRMS以及X射线单晶衍射等表征了配合物结构。测试了配合物C1、C2的热稳定性以及配合物对癌细胞H460、HepG2、MCF7的体外抑制活性;在Tris-HCl缓冲溶液中,以EB做为荧光探针,用荧光光谱法初步研究了配合物C1与小牛胸腺DNA的相互作用;并且用凝胶电泳法研究了配合物C1切割质粒DNA pBR322的能力。结果表明:配合物C1、C2对3种癌细胞都有较好的抑制作用,但是C1更优于C2;配合物C1与小牛胸腺DNA作用是插入结合作用所致,能有效的将超螺旋DNA pBR322切割成缺刻型DNA。     

2-羰基丙酸芳甲酰腙二对甲基苄基锡配合物的合成、晶体结构及生物活性

在含水甲苯中,对甲基氯苄与锡粉反应合成了二对甲基苄基二氯化锡,将其分别与2-羰基丙酸苯甲酰腙及2-羰基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物（1、2）,通过元素分析、IR、¹H NMR、¹³C NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞MCF-7、HepG2、NCI-H460以及正常人体肝细胞HL-7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB作为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明：配合物1、2对3种癌细胞都有明显的抑制作用,配合物2对HL-7702的细胞毒性小于1;配合物1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物2与小牛胸腺DNA作用是插入结合作用所致。     

2-羰基丙酸芳甲酰腙二对甲基苄基锡配合物的合成、晶体结构及生物活性

在含水甲苯中,对甲基氯苄与锡粉反应合成了二对甲基苄基二氯化锡,将其分别与2-羰基丙酸苯甲酰腙及2-羰基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物(1、2),通过元素分析、IR、1H NMR、13C NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞MCF-7、Hep G2、NCI-H460以及正常人体肝细胞HL-7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB作为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明:配合物1、2对3种癌细胞都有明显的抑制作用,配合物2对HL-7702的细胞毒性小于1;配合物1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物2与小牛胸腺DNA作用是插入结合作用所致。     

Synthesis,interaction with double-helical DNA and biological activity of new Pt(II) and Pd(II) complexes with phenylglycine

The mononuclear palladium(II) (1) and platinum(II) (2) complexes containing phenylglycine have been synthesized and characterized by elemental analysis, IR spectra, and ¹H NMR spectra. The structure of 1 was determined by X-ray diffractometry. The interaction between the complexes and fish sperm DNA (FS-DNA), adenosine-5′-triphosphate (ATP), and adenine (Ade) were investigated by UV absorption spectra, the interaction mode of the complex binding to DNA was studied by fluorescence spectra and viscometry. The results indicate that the two complexes have different binding affinities to DNA, complex 2 > complex 1. Gel electrophoresis assay demonstrates that the two complexes have the ability to cleave pBR322 plasmid DNA. Cytotoxicity experiments were carried out toward four different cancer cell lines, and 1 shows lower inhibitory efficiency than 2, consistent with the binding affinities towards DNA.     

2-羰基-3-苯基丙酸芳甲酰腙二(2,4-二氯苄基)锡配合物的合成、晶体结构及生物活性

二(2,4-二氯苄基)二氯化锡分别与2-羰基-3-苯基丙酸苯甲酰腙及2-羰基-3-苯基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物(C1、C2),通过元素分析、IR、1H NMR、13C NMR、119Sn NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞Hela、MCF7、Hep G2、Colo205、NCI-H460以及正常人体胚肾细胞HEK293、正常人体肝细胞HL7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB做为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明:配合物C1、C2对5种癌细胞都有明显的抑制作用,配合物C2对HEK293、HL7702的细胞毒性远小于C1;配合物C1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物C2与小牛胸腺DNA作用是插入结合作用所致。     

Synthesis,structure, DNA binding studies and nuclease activities of two luminescent neodymium complexes

Two neodymium(III) complexes, [Nd(Phen)(NO₃)₃(DMF)₂] (1) and [Nd(Phen)₂(NO₃)₃] (2) (phen = 1,10-phenanthroline; DMF = dimethylformamide), have been synthesized with a view to design artificial luminescent nucleases and nuclease mimics. The complexes were characterized by spectroscopic, powder, and single crystal XRD studies. The complexes, as expected, have luminescent properties. The DNA binding studies of both complexes have been carried out by spectroscopic studies e.g. electronic absorption (UV–Vis), fluorescence emission as well as viscosity measurements. The nuclease activity of the complexes has been established by gel electrophoresis using pUC19 circular plasmid DNA. The results of DNA binding as well as DNA cleavage activity and the model studies of interaction with pNPP indicate that both neodymium complexes demonstrate nuclease activity through phosphoester bond cleavage.     

2-羰基-3-苯基丙酸芳甲酰腙二(2,4-二氯苄基)锡配合物的合成、晶体结构及生物活性

二（2,4-二氯苄基）二氯化锡分别与2-羰基-3-苯基丙酸苯甲酰腙及2-羰基-3-苯基丙酸水杨酰腙反应,合成了2个取代苄基锡配合物（C1、C2）,通过元素分析、IR、¹H NMR、¹³C NMR、¹¹⁹Sn NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞Hela、MCF7、HepG2、Colo205、NCI-H460以及正常人体胚肾细胞HEK293、正常人体肝细胞HL7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB做为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明：配合物C1、C2对5种癌细胞都有明显的抑制作用,配合物C2对HEK293、HL7702的细胞毒性远小于C1;配合物C1与小牛胸腺DNA作用是插入结合与静电结合共同作用所致,配合物C2与小牛胸腺DNA作用是插入结合作用所致。     

Complex formation of cyclodextrins with poly(propylene glycol) derivatives

The complex formation between cyclodextrins (CDs) and poly(propylene glycol) (PPG) derivatives is described. β‐CD and γ‐CD formed complexes with PPG derivatives such as 1‐naphthyl (1NA), 2‐naphthyl (2NA), 3,5‐dinitrobenzoyl, and 2,4‐dinitrophenyl PPG. α‐CD did not form complexes with these PPG derivatives. Although γ‐CD gave complexes with 9‐anthryl PPG (PPG9An), β‐CD did not efficiently form complexes with PPG9An. β‐CD did not form complexes with trityl PPG, demonstrating that trityl groups were too bulky to thread a β‐CD cavity. The emission spectra of the complexes showed that β‐CD bound a single 2NA moiety in its cavity and that γ‐CD included two 2NA moieties. In contrast, γ‐CD bound a single 1NA moiety in the cavity. X‐ray diffraction studies and ¹H NMR analysis showed that the CD molecules were stacked along a PPG chain to form a channel structure. The inclusion modes are discussed. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 4839–4849, 2000     

Photosynthetic reactions in fullerene based donor-acceptor complexes

Donor-acceptor interaction changes essentially the terms of the ground state of binary complexes imparting them a multi-well, in particular, two-well form. A quantum chemical analysis of formation conditions for the amine derivatives of fullerenes depending on the type of the term has been performed by the example of binary complexes, including fullerenes C₆₀ and C₇₀ as acceptors of electrons and amines as donors,. It is found that the addition reaction of amines to fullerene hampered between neutral molecules can occur when the latter are ionized by light.     

Synthesis and characterization of diorganotin(IV) derivatives from rhodanine (HRd): crystal structures of [(PhCH2)2Sn(Rd)(μ-OH)]2 and [n-Bu2Sn(Rd)(μ-OH)]2

The diorganotin(IV) complexes, [R₂Sn(Rd)(μ-OH)]₂ (R?=?Me (1), PhCH₂ (2), n-Bu (3), Ph (4); HRd?=?rhodanine), have been synthesized and characterized by IR and multinuclear (¹H, ¹³C, ¹¹⁹Sn) NMR spectroscopy. The structures of complexes 2 and 3 have been determined by single-crystal X-ray diffraction. Both crystal structures of 2 and 3 show the presence of asymmetrically bridging hydroxy groups leading to an Sn₂O₂ unit. Each atom in complex 1 is also coordinated by an N atom of ligand and two C atoms of the alkyl groups, so the Sn environment is based on a trigonal bipyramid. While in complex 2, a weak intermolecular Sn–O interaction has also been found between the two adjacent molecules, so the geometry of the Sn atom can be best described as six-coordinate octahedral. The salient feature of the supramolecular structure of complex 3 is that of a 1D polymer, in which the discrete molecules are connected through weak intermolecular Sn?···?O interactions.     

Pharmacological properties of dicyanidoaurate(I)-based complexes: characterization and single crystal X-ray analysis

The synthesis of three bimetallic cyanido complexes with edbea [2,2′-(ethylenedioxy)bis(ethylamine)] ligand is reported. [Ni^II(μ-edbea)₂{Au(μ-CN)₂}₂]_n (1), [{Cu^II(edbea)}₂{Au(μ-CN)₂}₄]_n (2) and [Cd^II(edbea)₂][Au(CN)₂]₂·H₂O (3) were fully characterized by elemental, infrared, XRD (3), ESI-MS and thermal analysis. The DNA/BSA binding properties of these complexes were evaluated by spectrophotometric titration, fluorometric ethidium bromide kinetics, and DNA electrophoresis studies and their partially minor groove binding mode between the base pairs of DNA and electrostatic interaction between the amino acid residues of BSA were explained. The complexes were tested for their pharmacological properties. These molecules had excellent in vitro antiproliferative activity and also exhibited a strong tumor inhibiting effect against HT29, HeLa, C6 and Vero cell lines. These complexes had metastatic features as they are able to reduce cell migration activity and suppress tumor growth in vitro. Analysis of the DNA topoisomerase I relaxing activity indicates that the complexes do not inhibit topoisomerase I which regulates the topological states of the DNA double helix during DNA processing reactions. The TUNEL and DNA laddering assay results indicated that these compounds may destroy cell maintenance by triggering apoptosis. Immunohistochemistry staining analysis demonstrated that these complexes significantly decreased the expression of Bcl-2 in HeLa and HT29 cells while increasing the expression of P53 levels. Overall, the potent antiproliferative activity, low cytotoxic effect, good solubility, and micro molar range dosage observed for these complexes emphasizes their potential as anticancer drug candidates.     

N-(2-丙酸)-芳甲酰腙二对甲基苄基锡配合物的合成、晶体结构及生物活性

二对甲基苄基二氯化锡分别与N-（2-丙酸）-对硝基苯甲酰腙及N-（2-丙酸）-对叔丁基苯甲酰腙反应,合成了2个取代二苄基锡配合物（C1、C2）,通过元素分析、IR、UV-Vis、¹H NMR、¹³C NMR、¹¹⁹Sn NMR、X射线单晶衍射以及热重分析等表征了配合物结构。测试了配合物对癌细胞H460、HepG2、MCF7以及正常人体肝细胞HL7702的体外抑制活性;在Tris-HCl缓冲溶液中,以EB作为荧光探针,用荧光光谱法初步研究了配合物与小牛胸腺DNA的相互作用。结果表明：配合物C1、C2对3种癌细胞都有较好的抑制作用,配合物C2对HL7702的细胞毒性远小于C1;配合物C1、C2与小牛胸腺DNA作用均是插入结合作用所致。     

Interaction between methyl and hydroxyl radicals: a theoretical study

In this paper, we conduct a computational quantum mechanic study of two molecules interaction between methyl (·CH₃) and hydroxyl (·OH) radicals. The molecular exploration has been focused on the possibility of finding non-bonding interactions (formation of complexes by weak-bond interaction among C–O–H atoms) and the potential energy reaction between those two molecules. It shows that the formed complexes presents in slightly lower potential energy than that of the reactants and/or products. The existence of these complexes could proceed to the further interaction, e.g. reaction of the molecules, as those complexes formed a particular configuration.     

Estimation of the molecular weights of noncovalent columnar polymers based on β-cyclodextrin by the measurement of the aggregation rate of their polymer inclusion complexes with polypropylene glycol

Noncovalent columnar polymers (NCPs) based on cyclodextrins (CD) are polymeric assemblies of molecules that have continuous hollow channels, the width of which is determined by the diameter of the cavity of the initial CDs. The repeating fragment in an NCP is the CD molecule. For NCPs that were obtained by the exclusion of polymer backbone macromolecule from the corresponding inclusion complexes (ICs) based on β-cyclodextrin (NCP_excl), the polymer length, expressed as the number of macrocycles in a single chain (n) is determined by the size of the included ligand, polypropylene glycol (PPG), and is the PPG polymerization degree divided by two. The determination of the molecular weight of an NCP obtained by the precipitation method (NCP_prec) is rather difficult, since they are present in the aggregated state rather than in the form of individual molecules in solution. To estimate the molecular weight of NCP_prec, an indirect method is used, which is based on the determination of the aggregation rate of the ICs formed as a result of the interaction between an NCP and polypropylene glycol with a fixed molecular weight (MW), in this case PPG 1000. The comparison of the aggregation rates of the inclusion between NCP_excb (which were synthesized using PPGs with different molecular weights) and PPG 1000 with the aggregation rate of the inclusion complex on the basis of NCP_prec provided the estimation for the MWs of single polymer chains. The fact that the samples of NCPprec contain ∼30% of the monomeric β-CD was taken into account when constructing the calibration curve. It was demonstrated that the MW of the polypropylene glycol corresponding to NCP_prec is 1320 Da. Consequently, ∼11–12 molecules of β-CD are included in the single chains of NCP_prec.     

Heteroleptic Pd(II) dithiocarbamates: synthesis,characterization, packing and in vitro anticancer activity against HeLa cell line

Two new heteroleptic Pd(II) dithiocarbamates (1 and 2) have been synthesized by reaction of equimolar quantities of palladium(II) chloride, sodium 4-(3-methoxyphenyl)piperazine-1-carbodithioate, and appropriate substituted triphenylphosphines. The synthesized complexes have been characterized by their physical, spectral (IR, ¹H, ¹³C, and ³¹P NMR), and X-ray crystallographic data. Complexes 1 and 2 showed square-planar geometry both in solution and solid states. The crystal packing of both complexes revealed similar 3-D-supramolecular networks comprised of 1-D chains. However, the nature and strength of various non-covalent interactions of these networks were slightly different. The DNA interaction studies of the complexes have been carried out by UV–visible spectroscopy to evaluate their anticancer potential. The study suggested intercalative interaction with 2.402 × 10⁴ and 2.713 × 10³ M^?1 binding constants, respectively. The complexes have also been evaluated for their anticancer activity against HeLa cell line. Both complexes showed higher activity with IC₅₀ values much lower (22.176 and 26.166 μM for 1 and 2, respectively) than the standard cisplatin (78.075 μM). Furthermore, the complexes induced stronger DNA fragmentation as investigated by DNA ladder assay for apoptosis. Our findings suggested that the anticancer action of these compounds stems from their interaction with DNA leading to DNA damage and apoptosis. The excellent activity of 1 and 2 deserves to be a focus for further research and in vivo studies.