Differential interaction of Fluorescein-ß-cyclodextrin conjugate to quadruplex kit22 DNA: Inclusion of Berberine and modulation of binding.

Clinical applicability of G-quadruplexes as anticancer drugs is an area of current interest. Identification of supramolecular systems for selective targeting G-quartets is particularly intriguing. In this work, the DNA binder Berberine is encapsulated inside the molecular cavity of the synthesised host structure, Fluoresecein-ß-cyclodextrin conjugate. The host: guest complex is characterized and the mode of binding is optimized using two dimensional rotating-frame Overhauser effect spectroscopy. The conjugate is examined for its binding to quadruplex DNAs viz., kit22, myc22, telo24 and the duplex calf-thymus DNA before and after Berberine encapsulation. UV-vis and fluorescence spectroscopic methods were employed to determine the strength of binding of the complex with the DNAs. The binding strength and the stoichiometry of the host: guest complex are 1.9 × 106 mol-1 dm3 and 1:1, respectively. A quenching of fluorescence of the quadruplex kit22 and duplex ctDNA is observed on binding to the Fluorescein-ß-cyclodextrin conjugate. The quadruplexes of myc22 and telo24 display an enhanced fluorescence on binding to the modified cyclodextrin. The Stern-Volmer quenching constants are 1.4 × 106 mol-1 dm3 and 3.8 × 105 mol-1 dm3 for binding to kit22 and ctDNA respectively. kit22 shows a different emission profile on interacting with the Berberine encapsulated conjugate, whereas all the other quadruplexes and duplex exhibit similar emission profiles. The results indicate a variation in the binding mode and strength of the ligand-quadruplexes and depend on the conformation of the quadruplexes.Communicated by Ramaswamy H. Sarma.

G-Quadruplex binding of cavity-containing anthraquinonesulfonyl-ß-cyclodextrin conjugate. Effect of encapsulation of ethidium bromide and berberine.

An anthraquinonesulfonyl derivative of ß-cyclodextrin is prepared and characterized employing spectroscopic techniques. The binding interactions of the compound with ethidium bromide, berberine, calf-thymus DNA, quadruplex DNAs viz., kit22, telo24, and myc22 are investigated by ultraviolet-visible, and fluorescence spectroscopic methods. Anthraquinonesulfonyl-ß-cyclodextrin conjugate acts as a host molecule and enhances ethidium bromide and berberine fluorescence due to their encapsulation in cyclodextrin's cavity. The binding constant values are 9.0 × 105 mol-1 dm3 and 5.7 × 104 mol-1 dm3 for the formation of host: guest complexes of the ß-CD derivative with ethidium bromide and berberine respectively. The proximity of the protons of ethidium bromide and berberine protons with those of the internal cavity of ß-CD in the anthraquinonesulfonyl-ß-CD conjugate is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy. The conjugate displays a quenching of fluorescence selectively to the quadruplexes kit22 and telo24 that is contrast to the spectral behavior with duplex DNA. ctDNA and myc22 exhibit different absorption and emission profiles with ethidium bromide on encapsulation by ß-CD. The encapsulation of berberine leads to a fluorescence enhancement on binding to ctDNA, telo24, and myc22 with binding constants of 5.6 × 105, 3.3 × 105 mol-1 dm3, and 1.5 × 105 mol-1 dm3 respectively. In contrast, kit22 leads to fluorescence quenching on berberine encapsulated-anthraquinonesulfonyl-ß-cyclodextrin conjugate with a Stern-Volmer constant of 3.3 × 105 mol-1 dm3.Communicated by Ramaswamy H. Sarma.

Molecular encapsulation of berberine and ethidium bromide in anthraquinonecarboxamido-ß-cyclodextrin conjugate: supramolecular association with DNA duplex and G-quadruplexes.

G-quadruplex DNA in recognized as a potential target for anti-cancer drugs. In this work, an anthraquinonecarboxamido derivative of ß-cyclodextrin (AQCC) is synthesized as a novel DNA binder that further can deliver an additional molecule at the target, carrying it in the cavity of modified cyclodextrin. The binding of AQCC with ethidium bromide (EtBr), berberine (Ber), duplex calf-thymus DNA (CT-DNA), quadruplexes (G4) viz., kit22, myc22, and telo24 are studied. The compound acts as a host molecule for the encapsulation of DNA binders viz., EtBr, Ber and enhances their fluorescence due to the encapsulation in its AQCC's cyclodextrin cavity. The binding constant of the host: guest complex of EtBr and Ber with AQCC's cavity are 6.4 × 105 and 3.3 × 106 mol-1 dm3, respectively. The proximity of the protons of the guest and host molecules is confirmed by two-dimensional rotating-frame Overhauser effect spectroscopy (2D ROESY). The conjugate displays a quenching of fluorescence selectively on the association with CT-DNA and quadruplex kit22 that is contrast to the spectral behavior with quadruplex myc22 and telo24. CT-DNA exhibits dissimilar fluorescence spectra in free- and EtBr-bound forms. In addition, kit22 exhibit dissimilar emission profile when AQCC encapsulates Ber. Therefore, the Ber-loaded complexes and the AQCC molecule bind to different G-quadruplexes with different binding strengths. In addition, the effect of Ber in binding to the target DNAs is pronounces since the Ber molecule has more affinity to bind to quadruplexes than the duplex.

Chemico-biological interaction of Etravirine and its ß-Cyclodextrin complex with macromolecular targets.

The interaction of etravirine with ß-cyclodextrin is analyzed by UV-visible absorption, infrared, fluorescence, nuclear magnetic resonance, two-dimensional rotational frame nuclear Overhauser effect spectroscopy, and molecular modeling studies. The 4-hydroxy-3, 5-dimethylbenzonitrile moiety is found to take part in the binding. The stoichiometry of the inclusion complex of ET with ß-CD is 1:1 with the binding constant of 2.03 × 103 mol-1 dm3. The binding of ET with calf thymus DNA (ctDNA) and bovine serum albumin (BSA) protein is investigated in the presence and the absence of ß-CD. Fluorescence enhancement is observed during the binding of ET with ctDNA in the absence of ß-CD, whereas in the presence of ß-CD, fluorescence quenching is observed. The binding constants of the binding of ET and ET-ß-CD to ctDNA are 7.84 × 104 and 4.38 × 104 mol-1 dm3, respectively. The binding constant of the binding of ET and ET-ß-CD to BSA are 3.14 × 104 and 1.6396 × 104 mol-1 dm3, respectively. The apparent binding constants between ET-ß-CD complex and ctDNA or BSA protein decreases significantly. The numbers of binding sites of interaction of ET with BSA protein and the binding distance between BSA protein and ET the absence and the presence of ß-CD differ. ß-CD modulates the binding of ET with the macromolecular targets.

On the accessibility of surface-bound drugs on magnetic nanoparticles. Encapsulation of drugs loaded on modified dextran-coated superparamagnetic iron oxide by ß-cyclodextrin.

We report the loading of drugs on aminoethylaminodextran-coated iron oxide nanoparticles, their superparamagnetic behavior, loading of drugs on them, and the ß-cyclodextrin-complex formation of the drugs on the surface of the nanoparticles. The magnetic behavior is studied using vibrating sample magnetometry and X-ray photoelectron spectroscopy is used to analyze the elemental composition of drug-loaded nanoparticles. Scanning electron microscopy shows ordered structures of drug-loaded nanoparticles. UV-visible absorption and fluorescence spectroscopy are used to study the binding of the surface-loaded drugs to ß-cyclodextrin. All of the drugs form 1:1 host-guest complexes. The iodide ion quenching of fluorescence of free- and iron oxide-attached drugs are compared. The binding strengths of the iron oxide surface-loaded drugs-ß-cyclodextrin binding are smaller than those of the free drugs.

Picking Out Logic Operations in a Naphthalene ß-Diketone Derivative by Using Molecular Encapsulation, Controlled Protonation, and DNA Binding.

On-off switching and molecular logic in fluorescent molecules are associated with what chemical inputs can do to the structure and dynamics of these molecules. Herein, we report the structure of a naphthalene derivative, the fashion of its binding to ß-cyclodextrin and DNA, and the operation of logic possible using protons, cyclodextrin, and DNA as chemical inputs. The compound crystallizes out in a keto-amine form, with intramolecular N-H⋅⋅⋅O bonding. It shows stepwise formation of 1:1 and 1:2 inclusion complexes with ß-cyclodextrin. The aminopentenone substituents are encapsulated by ß-cyclodextrin, leaving out the naphthalene rings free. The binding constant of the ß-cyclodextrin complex is 512 m(-1). The pKa value of the guest molecule is not greatly affected by the complexation. Dual input logic operations, based on various chemical inputs, lead to the possibility of several molecular logic gates, namely NOR, XOR, NAND, and Buffer. Such chemical inputs on the naphthalene derivative are examples of how variable signal outputs based on binding can be derived, which, in turn, are dependent on the size and shape of the molecule.

Chromenone-conjugated magnetic iron oxide nanoparticles. Toward conveyable DNA binders.

Magnetic nanoparticles can transport drug and possibly target cancer. DNA-binding of ligands loaded in dextran coated magnetic nanoparticles, could aid their better target-specific binding. In this work, we report the loading of chromenones onto aminoethylamino-modified dextran coated iron oxide nanoparticles, their loading efficiency, and openness for binding to DNA. The magnetic behavior, the size, and the morphology of the nanoparticles are analyzed. The crystallite size of the magnetic nanoparticles is around 40 nm. The chromenones are present on the surface of the dextran shell, as revealed by their cyclodextrin-binding characteristics, which is a new approach in comprehending the accessibility of the surface-bound molecules by macromolecules. The mode of binding of the chromenones to DNA is not altered on surface loading on dextran shell, although the binding strength is generally diminished, compared to the strength of binding of the free chromenones to DNA.

Sheehan's Syndrome Presenting as Major Depressive Disorder.

Sheehan's syndrome or Simmond's disease is a rare endocrine disorder seen in clinical practice. The clinical spectrum is diverse and a high index of suspicion together with a good clinical acumen and proper diagnostic approach helps in early diagnosis and prompt treatment of this endocrinopathy. Sheehan's syndrome presenting as a major depressive disorder finds less mention in the literature. The patient discussed here is a 45-year-old female who had been on antidepressants and psychiatry follow up for a long time until she presented to our Out Patient Department (OPD), where she was evaluated in detail and diagnosed as a case of Sheehan's syndrome. The patient is doing well and is on a regular follow-up with us. Further studies are required to demystify the strength of this association in more detail and to elucidate the possible underlying mechanism.

Mode of encapsulation of linezolid by ß-cyclodextrin and its role in bovine serum albumin binding.

We describe, in this article, the associative interaction between Linezolid and ß-Cyclodextrin, and the influence of ß-Cyclodextrin on Linezolid's binding to Bovine serum albumin. ß-Cyclodextrin forms a 1:1 inclusion complex with Linezolid, with a binding constant value of 3.51×10(2)M(-1). The binding is studied using ultraviolet-visible absorption, fluorescence, nuclear magnetic resonance, and rotating-frame overhauser effect spectroscopic techniques. The amide substituent on the oxazolidinone ring of Linezolid is involved in its binding to ß-Cyclodextrin. The binding of the Linezolid to bovine serum albumin, in the absence and the presence of ß-Cyclodextrin, is studied by analyzing the fluorescence quenching and Förster resonance energy transfer. The Stern-Volmer quenching constant, the binding constant, and energy transfer occurring on the interaction of the Linezolid with BSA are found to be smaller in the presence of ß-Cyclodextrin than in water.

Binding interactions of naringenin and naringin with calf thymus DNA and the role of ß-cyclodextrin in the binding.

The interaction of naringenin (Nar) and its neohesperidoside, naringin (Narn), with calf thymus deoxyribonucleic acid (ctDNA) in the absence and the presence of ß-cyclodextrin (ß-CD) was investigated. The interaction of Nar and Narn with ß-CD/ctDNA was analyzed by using absorption, fluorescence, and molecular modeling techniques. Docking studies showed the existence of hydrogen bonding, electrostatic and phobic interaction of Nar and Narn with ß-CD/DNA. 1:2 stoichiometric inclusion complexes were observed for Nar and Narn with ß-CD. With the addition of ctDNA, Nar and Narn resulted into the fluorescence quenching phenomenon in the aqueous solution and ß-CD solution. The binding constant K(b) and the number of binding sites were found to be different for Nar and Narn bindings with DNA in aqueous and ß-CD solution. The difference is attributed to the structural difference between Nar and Narn with neohesperidoside moiety present in Narn.

Isolation of Prunin from the fruit shell of Bixa orellana and the effect of ß-cyclodextrin on its binding with calf thymus DNA.

Naringenin-7-O-glucoside [Prunin (Pru)] was isolated from the fruit shell of Bixa orellana L. The binding of Pru with calf thymus DNA (ctDNA) and the influence of cyclomaltoheptaose (ß-cyclodextrin, ß-CD) on the binding were studied by absorption and fluorescence spectroscopic techniques. The comparison of the binding modes of Pru/ß-CD and ctDNA-Pru/ß-CD suggested that ß-CD extracted Pru from DNA for forming inclusion complex. Molecular modeling gave added support to the above results. Fluorescence microscopy was used to visualize the effect of ß-CD on the bindings.

The influence of ß-cyclodextrin encapsulation on the binding of 2'-hydroxyflavanone with calf thymus DNA.

Inclusion complexation of 2'-hydroxyflavanone (2'HF) with ß-cyclodextrin (ß-CD) was studied, both in solution phase and as solid inclusion complexes, by UV-visible and fluorescence spectroscopic, scanning electron microscopic and X-ray diffractometric techniques. The interaction of 2'HF with calf thymus DNA (ctDNA) in the presence and the absence of ß-CD were compared. Fluorescence enhancement was observed for 2'HF due to the formation of 1:1 complex with ß-CD. The structure of 1:1 complex is proposed based on spectral observation, molecular modeling and by calculated theoretical bond lengths. The possible mode of interaction between 2'HF and DNA was analyzed by molecular modeling method. The interaction of 2'HF with calf thymus DNA (ctDNA) was investigated by absorption and fluorescence measurements in the presence and the absence of ß-CD as capping agent. Both in the presence and the absence of ß-CD, 2'HF showed hyper-chromic effect, red shift of absorption spectra, and quenching of fluorescence due to binding of 2'HF with ctDNA. The results reveal that the phenolic moiety is involved in inclusion complexation with ß-CD and interaction with DNA. In the presence of ß-CD, the phenolic moiety may be included in cyclodextrin cavity, whereas the dihydrobenzopyran-4-one moiety interacts with DNA. Further, ß-CD selectively blocks a part of the 2'HF molecule binding with DNA. This renders the remaining portion of the flavanone available for interaction with DNA.