Subramani Karthikeyan

Insights into the binding of thiosemicarbazone derivatives with human serum albumin: spectroscopy and molecular modelling studies.

4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl acetate [Ace semi],4-[(1Z)-1-(2-carbamothioylhydrazinylidene)ethyl]phenyl propanoate [Pro semi] from the family of thiosemicarbazones derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and it is also less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiosemicarbazone derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance (r) between donor (HSA) and acceptor (thiosemicarbazone derivative) was estimated according to Forster’s theory of non-radiative energy transfer using fluorescence spectroscopy. The binding dynamics has been elaborated using synchronous fluorescence spectroscopy, and the feature of thiosemicarbazone derivative induced structural changes of HSA has been studied by circular dichorism, Fourier transform infrared spectroscopy. Molecular modelling simulations explore the hydrophobic interaction and hydrogen bonding which stabilizes the interaction.

Determination on the binding of thiadiazole derivative to human serum albumin: a spectroscopy and computational approach

4-[3-acetyl-5-(acetylamino)-2,3-dihydro-1,3,4-thiadiazole-2-yl]phenyl benzoate from the family of thiadiazole derivative has been newly synthesized. It has good anticancer activity as well as antibacterial and less toxic in nature, its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of thiadiazole derivative to human serum albumin (HSA) has been investigated by studying its quenching mechanism, binding kinetics and the molecular distance, r between the donor (HSA) and acceptor (thiadiazole derivative) was estimated according to Forster’s theory of non-radiative energy transfer. The Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) changes of temperature-dependent Kb was calculated, which explains that the reaction is spontaneous and exothermic. The microenvironment of HSA have also been studied using synchronous fluorescence spectroscopy, and the feature of thiadiazole derivative-induced structural changes of HSA have been carried using Fourier transform infrared spectroscopy and the Molecular modelling simulations explore the hydrophobic and hydrogen bonding interactions.

Investigation of Optical Spectroscopic and Computational Binding Mode of Bovine Serum Albumin with 1, 4-Bis ((4-((4-Heptylpiperazin-1-yl) Methyl)-1H-1, 2, 3-Triazol-1-yl) Methyl) Benzene.

A newly synthesized 1, 4‐bis ((4‐((4‐heptylpiperazin‐1‐yl) methyl)‐1H‐1, 2, 3‐triazol‐1‐yl) methyl) benzene from the family of piperazine derivative has good anticancer activity, antibacterial and low toxic nature; its binding characteristics are therefore of huge interest for understanding pharmacokinetic mechanism of the drug. The binding of piperazine derivative to bovine serum albumin (BSA) was investigated using fluorescence spectroscopy. The molecular distance r between the donor (BSA) and acceptor (piperazine derivative) was estimated according to Forsters theory of nonradiative energy transfer. The physicochemical properties of piperazine derivative, which induced structural changes in BSA, have been studied by circular dichroism and those chemical environmental changes were probed using Raman spectroscopic analysis. Further, the binding dynamics was expounded by synchronous fluorescence spectroscopy and molecular modeling studies explored the hydrophobic interaction and hydrogen bonding results, which stabilize the interaction.

Underlying the Mechanism of 5-Fluorouracil and Human Serum Albumin Interaction: A Biophysical Study

5-Fluorouracil is clinically utilized as antitumor drug to treat numerous sorts of malignancy, which is made accessible to the objective tissues in conjugation with transport protein serum albumin furthermore which is low harmful when compared to the other drugs of this family and hence its binding characteristics are therefore of prime interest. The steady state and time resolved fluorescence studies, Fourier transform infrared spectroscopy and circular dichroism studies were employed to explain the mode and the mechanism of interaction of 5FU with HSA. 5-Fluorouracil binding is characterized with one high affinity binding site, with the binding constant of the order of 104. The molecular distance r (1.23 nm) between donor (HSA) and acceptor (5-FU) was estimated according to Forsters theory of non-radiative energy transfer. The feature of 5-Fluorouracil induced structural changes of human serum albumin has been studied in detail by Raman spectroscopy, circular dichroism and Fourier transform infrared spectroscopy analysis. The binding dynamics was expounded by synchronous fluorescence spectroscopy, fluorescence lifetime measurements and molecular modelling elicits that hydrophobic interactions and hydrogen bonding, stabilizes the 5-Fluorouracil interaction with HSA.

Effect of Moderate UVC Irradiation on Bovine Serum Albumin and Complex with Antimetabolite 5-Fluorouracil: Fluorescence Spectroscopic and Molecular Modelling Studies

The interaction of antimetabolite 5-fluorouracil (5FU) with bovine serum albumin (BSA) under UVC (253.7 nm) irradiation was investigated in the present study using UV-Vis spectroscopy, steady state/time resolved fluorescence spectroscopic techniques. The stability of protein was found to be very strong when BSA gets bind to 5FU and moreover it is compared with the free BSA under UVC irradiation. From the fluorescence spectroscopic study, the stability of the complex was found to acquire 2-fold stronger than free protein. From the molecular modelling studies, we came to know the hydrogen bonds between BSA and antimetabolite 5FU are strong, up to 70.4 J/m2 under UVC irradiation.

Investigations on the Interactions of 5-Fluorouracil with Herring Sperm DNA: Steady State/Time Resolved and Molecular Modeling Studies

In the present study, the interaction of 5-Fluorouracil with herring sperm DNA is reported using spectroscopic and molecular modeling techniques. This binding study of 5-FU with hs-DNA is of paramount importance in understanding chemico–biological interactions for drug design, pharmacy and biochemistry without altering the original structure. The challenge of the study was to find the exact binding mode of the drug 5-Fluorouracil with hs-DNA. From the absorption studies, a hyperchromic effect was observed for the herring sperm DNA in the presence of 5-Fluorouracil and a binding constant of 6.153 × 103 M-1 for 5-Fluorouracil reveals the existence of weak interaction between the 5-Fluorouracil and herring sperm DNA. Ethidium bromide loaded herring sperm DNA showed a quenching in the fluorescence intensity after the addition of 5-Fluorouracil. The binding constants for 5-Fluorouracil stranded DNA and competitive bindings of 5-FU interacting with DNA–EB systems were examined by fluorescence spectra. The Stern–Volmer plots and fluorescence lifetime results confirm the static quenching nature of the drug-DNA complex. The binding constant Kb was 2.5 × 104 L mol-1 and the number of binding sites are 1.17. The 5-FU on DNA system was calculated using double logarithmic plot. From the Forster nonradiative energy transfer study it has been found that the distance of 5-FU from DNA was 4.24 nm. In addition to the spectroscopic results, the molecular modeling studies also revealed the major groove binding as well as the partial intercalation mode of binding between the 5-Fluorouracil and herring sperm DNA. The binding energy and major groove binding as -6.04 kcal mol-1 and -6.31 kcal mol-1 were calculated from the modeling studies. All the testimonies manifested that binding modes between 5-Fluorouracil and DNA were evidenced to be groove binding and in partial intercalative mode.

4-Hydroxycoumarin Derivative: N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide Interaction with Human Serum Albumin

In this study, the interaction between the coumarin derivative: N-(diphenylmethyl)-2-[(2-oxo-2H-chromen-4-yl)oxy]acetamide, biologically active drug, and human serum albumin (HSA) was investigated by using various optical spectroscopy techniques along with the computational technique. The results of steady-state fluorescence spectroscopy show that the static quenching occurred while increasing the coumarin drug concentration into HSA. Also, the binding constant (K) and thermodynamical parameters of enthalpy change (ΔH°), entropy change (ΔS°), and Gibbs free energy change (ΔG°) were calculated at different temperatures (293 K, 298 K, and 303 K). The results are in good agreement with those of molecular docking studies, and also, the docking study was carried out to understand the hydrogen bonding and hydrophobic interaction between human serum albumin and coumarin derivative. In addition to the docking, charge distribution analysis was done to understand the internal stability of coumarin derivative active sites of human serum albumin. Further time-resolved emission spectroscopy (TRES) studies were carried out between free HSA and HSA-coumarin complex, and the result confirms the presence of the drug in the protein molecule without cytotoxicity.

(Z)-3-(2-Amino-anilino)-1-phenyl-but-2-en-1-one.

In the title compound, C16H16N2O, the phenyl and 2-aminophenyl rings are almost perpendicular to one another, with a dihedral angle of 82.77 (8)°. There is an intramolecular N—H⋯O hydrogen bond in the molecule. In the crystal, molecules are linked via N—H⋯O hydrogen bonds forming chains along [001]. There are also C—H⋯π interactions present, linking the chains to form a three-dimensional structure.