Cyclodextrins are toroidal oligosaccharides with six to eight D-glucose monomers. β-cyclodextrins (β-CD) having seven such monomer units find various applications as drug delivery vehicles as it forms stable inclusion complexes with small biologically active molecules. Here, we have chosen thymol, as it has antimicrobial, antibacterial and antioxidant activities owing to its phenolic structure. We have studied the behaviour of β-CD encapsulated thymol and its interaction with DNA and different cell lines. Various sets of β-CD encapsulated systems were prepared by Box–Behnken design. Morphology of the encapsulated systems have been characterised using TEM and stability of the systems were monitored using DLS. UV–visible spectroscopy indicates a hyperchromic shift upon gradual addition of DNA. Isothermal titration calorimetric experiments help to confirm the binding interactions between β-CD-thymol and DNA. Positive ∆H (+ 336 kJ mol−1) and ∆S (+ 1.176 kJ mol−1 K−1) values indicate hydrophobic interactions. Fluorescence spectroscopic studies showed emission intensity of the complex decreases gradually upon increasing addition of DNA. Temperature variance and time resolved fluorescence measurement support static quenching. Competitive displacement assay, iodide quenching and DNA melting studies suggest groove binding with DNA. By encapsulation technique, thymol can be safely delivered to the living cells. MTT assay was performed to see whether the encapsulation has impact on anticancer activity or not. Finally, ROS-H2O2 assay indicated that β-CD-thymol offers cell protection under oxidative stress.

The study of interaction between small molecule and biomacromolecule is highly important in the field of research in biochemistry, pharmaceutical and medicinal chemistry. Here bromelain, a pineapple-stem enzyme is taken as the biomacromolecule and its binding interaction with triazole-based organic molecules are investigated by steady state absorption and emission spectroscopy. The experimental results are supplemented by molecular docking. The triazoles are designed by mimicking the structure of Vorinostat which a bioactive compound. In this paper, we have explored the biophysical interaction of three triazole based ligands with cysteine protease enzyme bromelain for the very first time using steady-state fluorescence and temperature variation experimentally, also compared them with two of our previously published triazoles molecules (SSAM 1 as C-1 and SAM 1 as C-5). The triazole moiety in these compounds are found to be involved in pi-interactions and hydrogen bonding with the amino acid residues present in bromelain and provides stability to the bromelain-small molecule complexes. At lower temperature the binding of these compounds with bromelain becomes relatively more spontaneous. The study shows that the presence of triazole at terminal end in the molecule can make them an inhibitor of bromelain's proteolytic acitivity. But the presence of triazole at cap region provides better binding interaction of the ligand with bromelain under physiological condition.

Cisplatin, a platinum-based chemotherapeutic agent, has been used in the treatment of various cancers, including testicular, ovarian, lung, bladder, and cervical cancer, for over four decades. However, cisplatin’s clinical utility is often limited by its severe side effects, including nephrotoxicity, ototoxicity, neurotoxicity, and myelosuppression. In the present study, we have developed a liposomal system for encapsulation of the drug using the thin film hydration method. Pristine cholesterol-free cisplatin-loaded liposomes (FCLs), cisplatin-loaded lecithin-cholesterol liposomes (CLs), and chitosan-coated cisplatin-loaded CLs (CHCLs) were prepared using active loading method with the help of Box-Behnken design. The liposomes were characterized by evaluating particle size, zeta potential, TEM, and encapsulation efficacy. The release of cisplatin from the liposomal system was found to be in the order free cisplatin > FCLs > CLs > CHCLs. However, chitosan coating increased the encapsulation efficacy of cisplatin and the stability of the liposomal system. Moreover, CHCLs exhibit better cytotoxicity towards HeLa cells compared to CLs through the generation of more reactive oxygen species (ROS) leading to cell death. From isothermal calorimetric studies, it has been found that the interactions of cisplatin with the liposomal system were electrostatic in nature and the interaction of cisplatin encapsulated liposome with 0.25

We have semi-synthesized a natural product 7-acetylhorminone from crude extract of Premna obtusifolia (Indian headache tree), which is active against colorectal cancer after probation through computational screening methods as it passed through the set parameters of pharmacokinetics (most important nonblood-brain barrier permeant) and drug likeliness (e.g., Lipinski's, Ghose's, Veber's rule) which most other phytoconstituents failed to pass combined with docking with EGFR protein which is highly upregulated in the colorectal carcinoma cell. The structure of 7-acetylhorminone was confirmed by single crystal X-ray diffraction studies and H-1 NMR, C-13 NMR, and COSY studies. To validate the theoretical studies, first, in vitro experiments were carried out against human colorectal carcinoma cell lines (HCT116) which revealed the potent cytotoxic efficacy of 7-acetylhorminone and verified preliminary investigation. Second, the drugability of 7-acetylhorminone interaction with serum albumin proteins (HSA and BSA) is evaluated both theoretically and experimentally via steady-state fluorescence spectroscopic studies, circular dichroism, isothermal titration calorimetry, and molecular docking. In summary, this study reveals the applicability of 7-acetylhorminone as a potent drug candidate or as a combinatorial drug against colorectal cancer.

Study of interaction of small molecules with serum albumins is very much essential in the perspective of pharmaceutical and food chemistry. Triazoles are nitrogen containing heterocyclic organic compounds and can show binding interaction with the amino acid residues of proteins via mainly H-bonding using the nitrogen atoms. Here we have synthesized a triazole based organic compound tert-butyl(6-oxo-6-(((1-(2-oxo-2H-chromen-4-yl)-1H-1,2,3-triazol-4-yl) methyl)amino) hexyl)carbamate (SAM-1) using CuAAC reaction and investigated its interaction with serum albumins (BSA, HSA) and Bromelain (BMLN) using steady state fluorescence spectroscopy. The experimental results were further supplemented by Molecular docking. The theoretical ADMET (Absorption, Digestion, Metabolism, Excretion, Toxicity) predictions are also performed to check its drug-able nature. The experimental and theoretical studies indicate a good and spontaneous binding interaction (binding constant is of 10(5) order) of SAM-1 with both the serum albumins and Bromelain at 298K along with a good ADMET profile. As SAM-1 binds with Bromelain, it makes it suitable for oral absorption. In a nutshell SAM-1 can be considered as a potential drug candidate and can be further investigated for its medical effectiveness in future.

A novel 1,2,3-triazole-napthamide molecule (SSAM-1) is designed as per De-Novo drug design method and synthesized by using copper-catalyzed alkyne-azide cycloaddition reaction. The interaction studies of SSAM-1 with bovine serum albumin (BSA), human serum albumin (HSA) and bromelain (BMLN) are investigated by steady state fluorescence spectroscopic studies. The experimental results for these interaction studies are validated by molecular docking method. The theoretical prediction of ADMET properties of SSAM-1 are also performed using computational methods. All these studies indicate significant and spontaneous binding of SSAM-1 with serum albumins and BMLN at pH 7 under varying temperature conditions (288K, 298K, 308K). In all the three cases the interaction of the molecule with the proteins and enzymes led to quenching of the fluorescence emission (mainly via static quenching mechanism) of tryptophan (Trp) residue present in the proteins and in the enzyme. The complexation with SSAM-1 changes the microenvironment of the Trp residue(s) of BSA, HSA and BMLN. Strong binding affinity between proteins and SSAM-1 is indicated by the binding constant values, which is in 103-105 orders. Hydrophobic forces are acting as the major interacting forces for SSAM-1-HSA interaction while H-bonding and van der Waals forces are acting as the primary interacting forces for SSAM-1 interacting with BSA and BMLN. ADMET prediction reveals the drug-able nature of SSAM-1 which is justified due to its ability to bind with the serum albumins. In addition binding study of SSAM-1 with BMLN indicates its possibility of oral administration. Conducting such binding studies of the newly synthesized triazole with biomolecules, an effort is made to assess the contribution of a novel compound to the development of medicines for the drug design process at a very early stage of the research.

Dietary polyphenols offer a wide range of health benefits in functional food, nutraceutical, as well as pharma-ceutical industries. Their practical applications, however, encounter several challenges due to limited solubility and bioavailability. In the present study, we have developed a pH-driven method to prepare rutin-loaded lipo-somes which were characterized by evaluating particle size, polydispersity index (PDI), zeta potential, TEM, and encapsulation efficacy. The IC50 value of encapsulated rutin for HeLa cells was 250 mu mol/L, while free rutin shows insignificant inhibitory effect. Besides, the bioaccessibility of rutin enhanced from 9.8% to 19.7% upon liposomal encapsulation. The percentage release of free rutin in SGF and SIF was-98.4% and-98.7% respectively within 6 h. However, upon encapsulation, less than 55% was released even after 24 h. Overall, the enhanced bioaccessibility, reduced cell viability of HeLa cells, and most importantly, sustained release for rutin-loaded liposomes, accounted for the favorable outcome of our approach.

A polyphenolic acid assisted synthesis of Ni nano particles for absorption spectrophotometric sensing of MnO4- ions in micro molar range is reported here. The synthesis was carried out using a green approach where sinapic acid acts as a capping agent. The synthesized nano particle was then characterized using UV-Vis spectroscopy, Fourier transform infrared spectroscopy, transmission electron microscopy, powder X-ray diffraction analysis, X-ray photoelectron spectroscopy. The particle size is around 5 to 10 nm with the presence of both porosity and nano crystallinity as obtained from the transmission electron microscopic analysis. This nano particle can selectively sense permanganate ions in presence of different co-existing ions with the limit of detection (LOD) 0.413 mu M. The sensing mechanism was examined with the isothermal titration calorimetry (ITC) and X-ray photoelectron spectroscopy (XPS). Isothermal titration calorimetric data suggests that the interaction between permanganate and the nano particle is enthalpy driven process with Delta H and Delta G values are-80 kcal/mol and-5.72 kcal/mol respectively. XPS data confirmed the presence of Ni(II) ions in the Ni-SA NPs and the atomic percentage of the same differed in presence of KMnO4. There was no significant interference from the contemporary ions and even in the presence of Mn2+ ion. The method has also been applied for the natural water samples and for vegetable. similar to 88 to 108 % of the added KMnO4 could be recovered from the tap water sample using our prepared methodology. The limit of detection and the present technique are compared with the pre-viously reported literature and have been found to be comparable, even in solvent-free conditions and using simple instrumentation.

The self-assembly process of proteins provides plenty of potential for redesigning and combining them into supramolecular assemblies for real-time applications. The present study demonstrates the encapsulation of dietary polyphenol rutin in beta-casein (beta CN) micellar cavity followed by their molecular interactions and biological implications. The prepared rutin-loaded beta CN particles (DLS: 274.2 +/- 3.86 nm; TEM: similar to 200 nm) appeared to be smoothly spherical. Isothermal titration calorimetry (ITC) studies indicated that the encapsulation process was thermodynamically favorable and a typical example of entropy-driven hydrophobic interaction (Delta H: 38.1 kJ mol(-1); T Delta S = 51.9 kJ mol(-1) K-1). The molecular interaction of rutin with beta CN was characterized by absorption, steady-state fluorescence, and time-resolved fluorescence spectroscopic studies. The intrinsic fluorescence of beta CN was quenched by rutin via a static mechanism with a favorable binding affinity. Molecular docking studies suggested the involvement of hydrophobic and hydrogen bonding interactions between the concerned entities. A sustained release mechanism followed by significant improvement in the cytotoxicity of rutin was observed after encapsulation. An in vitro digestion model mimicking gastric and intestinal phases was also employed to study the bioaccessibility. Our study may assist in formulating more efficient casein-based carrier systems to enhance the bio-efficacy of polyphenols.

Plant-derived flavonoids are an excellent option as a potential substitute to synthetic products in food industries, and flavonoid-metal complexes exhibit better functional properties than free tlavonoids. Here, an iron(II) complex of rutin, a dietary flavonoid, has been synthesized and characterized. A comparative assessment of the interaction of rutin and its iron(II) complex with the transport protein [bovine serum albumin (BSA)] and deoxyribonucleic acid (DNA) has been performed. The interaction process has been characterized using multispectroscopic techniques and has been further supported by theoretical studies. We have evidenced the alteration in the interacting mode of rutin with BSA upon complexation with Fe(II). Also, rutin interacts with DNA via minor groove binding, while the complex interacts with DNA through a mixed mode involving both groove binding and intercalative binding. Interestingly, the antioxidant activity of the metal complex has been found to he enhanced, and it also provides better protection against UV radiation-induced cell damage than rutin alone.

Introduction: The UV radiation is known as a potential environmental carcinogen which causes damages of macromolecules like DNA, RNA, lipid, and protein inside the cell and eventually causes cell death. Persons who chronically exposed to UV radiation due to occupational or environmental exposure have a potential risk to develop cancer of the skin and internal organs. Polyphenols have a promising role in scavenging reactive oxygen species developed in our body due to a variety of exposure including radiation. In the present study, we are therefore evaluating the role of sinapic acid (SA), a polyphenol, in scavenging UV radiation-induced generation of reactive oxygen species and eventual cell death. We have studied the biological activity of SA as a potential antioxidant on human peripheral blood mononuclear cells taken from human volunteers. Methods : Graded concentration of SA in different solvent mediums was applied to UV exposed peripheral blood mononuclear cells for evaluating the best effective delivery system and concentration against UV radiation. Result: After series of experiments, we have observed that even at 10 µM concentration, SA is effective against UV induced cellular death. Conclusion: Finally, from this work we are inviting lots of works in this field to establish this molecule as a medicine to reduce radiation-induced cellular death.

AbstractNaturally occurring phenolic compounds (PCs) exhibit potential biological efficiencies and have potential applications in the food and pharmaceutical industries. Poor water solubility along with some other factors limits the usage of PCs in different industrial sectors. The bio‐efficacy of PCs is also affected due to their low water solubilities. Suitable encapsulating systems are thus required to maximize the water solubility and hence enhance the efficacies of bioactive PCs. Liposomal encapsulation is a good option as reflected in numerous research works. In this review, we have discussed different conventional methods and modified methods utilized to prepare PC‐loaded liposomes and the ensuing effect of encapsulation on the stability and bio‐efficacies of PCs. The encapsulation efficiencies of different methods have also been discussed. A comparative assessment of different methods applied for liposomal encapsulation of PCs and their effectiveness in enhancing bio‐efficacy is the key feature of this review.

3,5-Dimethoxy-4-hydroxycinnamic acid commonly known as Sinapic acid is a well-known derivative of hydroxycinnamic acids, is commonly present in human diet. Due to its wide variety of pharmacological activities like antioxidant, antimicrobial, anti-inflammatory, anticancer, and anti-anxiety, it has attracted much attention for the researchers. In our previous published work we have already analyzed the interaction between sinapic acid (SA) with a model transport protein. In this work our aim is to demonstrate a detailed investigation of the binding interaction between sinapic acid with another carrier of genetic information in a living cell, the DNA. Here we have used calf thymus DNA (ct-DNA) as a model. The binding characteristic of SA with ct-DNA was investigated by different spectroscopic and theoretical tools. The spectroscopic investigation revealed that quenching of intrinsic fluorescence of SA by ct-DNA occurs through dynamic quenching mechanism. The thermodynamic parameters established the involvement of hydrogen bonding and weak van der Waals forces in the interaction. Further, the circular dichroism, competitive binding experiment with ethidium bromide and potassium iodide quenching experiment suggested that SA possibly binds to the groove position of the ct-DNA. Finally, molecular docking analysis established the SA binds to minor groove position of ct-DNA in G-C rich region through hydrogen bonding interaction. Additionally, gel electrophoresis analysis has been performed to determine the protective efficacy of SA against UVB induced DNA damage and 50 μM of SA was found to protect the DNA from UVB induced damage. We hope that our study could provide the validation of SA on behalf of therapeutics and development of next generation therapeutic drug as well as designing new efficient drug molecule and methodology for the interaction study of the drug with DNA.

This work deals with the synthesis of biomolecule-based monometallic Ag and Pd and bimetallic Ag–Pd nanocomposites and their catalytic activity towards etherification reaction.

Introduction: Flavonoids are widely used as dietary supplements, and thus, play a significant role in the research field. In recent time, the interaction of flavonoid-metal complexes with serum albumin (SA) has widely been studied since the complexation poses a significant impact on biological activities. Additionally, the binding nature of flavonoids with SA gets modified in the presence of metal ions. Methods: In the present review, we studied the interaction of quercetin (Qu), a well-known flavonoid, and its Cu2+ complexes with SA to provide sufficient information about the beneficial role of metal-flavonoid complexes over free flavonoids. Results: Complexation with Cu(II) ion may alter the mode of binding of Qu with SAs. The strength of binding might be increased in the presence of Cu(II) as evidenced by the binding constant calculation. However, the drug binding site in bovine serum albumin (BSA) and human serum albumin (HSA) are not altered during the complexation process. Conclusion: To enhance the pharmaceutical outcomes of Qu molecules, one may use Qu-Cu(II) complex for the development and delivery of the small molecules.

Researches based on metal complexes of plant-derived phenolic acids have attracted much attention due to their beneficial applications in the development of functional food products, dietary supplements and pharmacology. Binding of phenolic acids with serum proteins greatly influences their pharmacological properties. In this context, interactions of a naturally occurring phenolic acid, sinapic acid (SA) and its Cu2+ complex with a model transport protein, bovine serum albumin (BSA), have been explored by means of different spectroscopic and theoretical tools. Spectroscopic studies revealed that the interaction of SA and its Cu2+ complex with BSA occurred through quenching of intrinsic fluorescence of BSA. Site-specific experimental and docking studies were performed to predict the binding site. The geometies of bound Cu2+ and interacting residues of protein were predicted from a solution dynamics study. Interestingly, the complexation of SA with Cu2+ enhanced the antioxidant activity of SA.

Increases in general circulatory time, half-life and bioavailability increase the efficacy of any drug molecule. Rutin (3, 3′, 4′, 5, 7 -pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid known for its ability to regulate cell metabolism, gene expression, and protect against oxidative stress, although certain biophysical aspects of their functioning are not yet clear. Non protein and small protein molecules with electrophilic properties are transported through the blood to their target site by binding with albumin. The authors therefore hypothesized that modification of rutin-albumin binding by changing the microenvironment in which it is delivered can increase the efficacy of the molecule. Therefore, the interaction of rutin in different solvent systems with albumin have been studied to evaluate the bioavailability and efficacy of the molecule to introduce it as a drug for combating UVB radiation-induced damage in biological systems. We evaluated the effect of rutin–albumin interaction in blood plasma in various modes of delivery (in DMSO, alcohol and PEG). The biological activity and efficacy of different solvents for rutin delivery and its bioavailability were studied using UVB irradiated human peripheral blood mononuclear cells in vitro. Amelioration of UVB radiation-induced oxidative damage and cell death by rutin has been studied by MTT assay and Tryphan blue exclusion assay and LDH-cytotoxicity assay. In these three studied systems the most effective concentration of rutin was also determined.

The crucial role of chemosensor for the immediate recognition of environment pollutant motivates the researchers to develop variety of sensing protocols. Of various chemosensory protocols, the colour change observed by the naked eye is considered to be a conceivable and on-site way to indicate the presence of an analyte. We herein report a colourimetric and commercially available absorption probe, sinapic acid (SA) that is completely ready to use for "on-site" visual determination of copper ions. The molecule, SA is well-known phenolic acid, often utilized for its antibacterial activity. In this work, for the first time, we are exploring its ability to work as an efficient Cu2+ sensor. This sensor molecule selectively detected Cu2+ ions by changing its colour from colourless to pink within detection limit of 64.5nM, which is much lower than other reported sensor molecules and the suggested limit by World Health Organization (WHO) and U. S. Environmental Protection Agency (EPA) guidelines. The sensing mechanism was investigated through UV-vis and 1H NMR titration along with ESI-MS spectroscopy and further confirmed by DFT computational studies. Studies revealed the participation of hydroxyl group (OH) and methoxy group (OMe) of SA in complexation with Cu2+. The binding stoichiometry of SA to Cu2+ was found to be 1:2 through Job's plot and ESI-MS analysis. Importantly, paper strips of SA were prepared which could be used for a rapid "on-site" determination of Cu2+ containing samples.

The binding interaction of Rutin, a flavonoid, with model transport proteins, bovine serum albumin (BSA) and human serum albumin (HSA), were investigated using different spectroscopic techniques, such as fluorescence, time-resolved single photon counting (TCSPC) and circular dichroism (CD) spectroscopy as well as molecular docking method. The emission studies revealed that the fluorescence quenching of BSA/HSA by Rutin occurred through a simultaneous static and dynamic quenching process, and we have evaluated both the quenching constants individually. The binding constants of Rutin-BSA and Rutin-HSA system were found to be 2.14 × 106 M-1 and 2.36 × 106 M-1 at 298 K respectively, which were quite high. Further, influence of some biologically significant metal ions (Ca2+, Zn2+ and Mg2+) on binding of Rutin to BSA and HSA were also investigated. Thermodynamic parameters justified the involvement of hydrogen bonding and weak van der Waals forces in the interaction of Rutin with both BSA and HSA. Further a site-marker competitive experiment was performed to evaluate Rutin binding site in the albumins. Additionally, the CD spectra of BSA and HSA revealed that the secondary structure of the proteins was perturbed in the presence of Rutin. Finally protein-ligand docking studies have also been performed to determine the probable location of the ligand molecule.