Sudit Mukhopadhyay

Ligand substitution reaction on a platinum(II) complex with bio-relevant thiols: kinetics, mechanism and bioactivity in aqueous medium

The kinetics of the interaction between [Pt(pic)(H2O)2](ClO4)2, cis-diaqua(2-aminomethylpyridine)platinum(II) perchlorate 1 and selected thiols (L-cysteine and N-acetyl-L-cysteine) has been studied spectrophotometrically in aqueous medium as a function of complex and thiol concentrations, pH, and temperature at constant ionic strength. The observed pseudo-first-order rate constants kobs (s−1) obeyed the equation kobs = k1[thiol]. At pH = 4.0, complex 1 interacts with the thiols via two distinct consecutive steps. The first step is dependent while the second step is independent of ligand concentration. The rate constants for the process are of the order: k1 ≈ 10−3 M−1 s−1 and k2 ≈ 10−5 s−1. The association equilibrium constant (KE) for the outer sphere complex formation has been evaluated together with the rate constants for the two subsequent steps. Both the steps are ligand-assisted anation and the final step is the ring closure process. The activation parameters for both steps were evaluated using Eyrings equation. The low ΔH‡1 = (34.91 ± 0.97 kJ mol−1) and ΔH‡2 = (29.10 ± 0.72 kJ mol−1) values and large negative values of ΔS‡1 = (−174.68 ± 2.18 J K−1 mol−1) and ΔS‡2 = (−233.74 ± 2.4 J K−1 mol−1) for both the anation steps were evaluated. On the basis of the kinetic observations, evaluated activation parameters and spectroscopic data, a plausible associative mechanism is proposed for both processes. Antibacterial properties on both gram positive and gram negative bacteria and anticancer properties of complex 1 and its substituted complexes 2 and 3 on HeLa cells have been investigated. Complexes 1 to 3 show remarkable growth inhibition of bacteria. They also show anticancer activity of about 70% when compared to cis-platin. The complexes bind to DNA and change its electrophoretic mobilization pattern in agarose gel.

Physico-chemical characterization and biological response of Labeo rohita -derived hydroxyapatite scaffold

The chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite (HAp) biomaterials. Thermogravimetric and differential thermal analyses of fish scale materials reveal the different phase changes with temperature and find out the suitable calcination temperatures. The composition and structures of wet ball-milled calcined HAp powders are characterized by Fourier transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray analysis (EDX). The EDX as well as chemical analysis of fish scale-derived apatite materials confirms that the Ca/P ratio is 1.71. The compressive stress, hardness and porosity have been evaluated on sintered HAp biomaterials. The cell attachment on HAp surfaces, cytotoxicity evaluation and MTT assay, which are carried out in RAW macrophage-like cell line media demonstrate good biocompatibility. The histological analysis also supports the bioaffinity of processed HAp biomaterials in Wistar rat model for investigating the contact reaction and stability at the artificial or natural prosthesis interface.

Interaction of bio-relevant thio-ether and thiols with dinuclear Pd(II) complex: kinetics, mechanism, bioactivity in aqueous medium and molecular docking

The kinetics of interaction between [Pd(pic)(OH)]2(ClO4)2, 2 (pic = 2-aminomethylpyridine) with the selected ligands (L) DL-methionine (DL-meth), L-cysteine (L-cys) and N-acetyl-L-cysteine (N-ac-L-cys) have been studied under pseudo-first order conditions using a stopped-flow spectrophotometer in aqueous medium as a function of [complex 2] as well as [ligand], pH, and temperature at constant ionic strength. The ligand dependent second order reaction is found to take place in two consecutive steps in accordance with the rate law, k(obs) = k1[L]2 in which all these three reactions follow the third order kinetics. The first step of the reaction is dependent, while the second step is independent of [ligand] in all the cases. The activation parameters, ΔH‡ and ΔS‡ for the two-step reactions are evaluated from the Eyring equation. An associative mode of activation (an associative mechanism) in the transition state is proposed for all these substitution processes. Complex 2 and its substituted products [Pd(pic)DL-meth]+ 3; [Pd(pic)L-cys] 4; and [Pd(pic)N-ac-L-cys] 5 are characterized by UV-Vis, FT-IR, 1H-NMR and ESI-mass spectroscopic methods. Complex 2–5 show remarkable anticancer properties on HeLa cells of about 70% at high concentration when compared to cis-platin and antibacterial properties on both the Gram positive (Bacillus subtilis) and Gram negative (E. coli Dh5α) bacteria. In addition, DNA interaction with plasmid DNA is observed and computational molecular docking studies were carried out with an aim to establish the binding mode of complex 2 with B-DNA.

A novel ditopic chemosensor for cadmium and fluoride and its possible application as a pH sensor

A urea-based BPC [1,5-bis(perfluorophenyl)carbonohydrazide] molecule with four acidic NH protons has been synthesized by a facile synthetic process. The molecule was found to be a ditopic chemosensor for Cd2+ and F− ions. BPC was synthesized from low-cost starting materials, dinitrophenyl hydrazine and triphosgene. The host–guest interactions between the ions (Cd2+ and F−) were not only confirmed by convenient spectroscopic techniques such as UV-Vis, PL, 1H-NMR, FT-IR, and cyclic voltammetry but also through modern DFT, the results of which were in good agreement with the experimental results. In vitro studies in human cancer cells (HeLa cells) were successfully performed with BPC and Cd2+ using fluorescence microscopy. The reversible UV-Vis response for BPC with F−, OH− and H+ mimics multiple logic functions and can be used for several complex electronic circuits based on logic operations. The pH sensor (BPC) can be further interfaced with suitable circuitry interfaced with appropriate programming for ease of access and enhancement of its practical applications.

Antagonistic molecular interactions of photosynthetic pigments with molecular disease targets: a new approach to treat AD and ALS

Abstract Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS) are progressive neurodegenerative diseases that affect the neurons in the brain and the spinal cord. Neuroinflamation and apoptosis are key players in the progressive damage of the neurons in AD and ALS. Currently, there is no drug to offer complete cure for both these diseases. Riluzole is the only available drug that can prolong the life time of the ALS patients for nearly 3 months. Molecules that offer good HIT to the molecular targets of ALS will help to treat AD and ALS patients. P53 kinase receptor (4AT3), EphA4 (3CKH) and histone deacetylase (3SFF) are the promising disease targets of AD and ALS. This paper discusses on a new approach to combat neurodegenerative diseases using photosynthetic pigments. The docking studies were performed with the Autodock Vina algorithm to predict the binding of the natural pigments such as β carotene, chlorophyll a, chlorophyll b, phycoerythrin and phycocyanin on these targets. The β carotene, phycoerythrin and phycocyanin had higher binding energies indicating the antagonistic activity to the disease targets. These pigments serve as a potential therapeutic molecule to treat neuroinflammation and apoptosis in the AD and ALS patients.

Insights from the Molecular Dynamics Simulation of Cellobiohydrolase Cel6A Molecular Structural Model from Aspergillus fumigatus NITDGPKA3.

Global demand for bioethanol is increasing tremendously as it could help to replace the conventional fossil fuel and at the same time supporting the bioremediation of huge volume of cellulosic wastes generated from different sources. Ideal genetic engineering approaches are essential to improve the efficacy of the bioethanol production processes for real time applications. A locally isolated fungal strain Aspergillus fumigatus NITDGPKA3 was used in our laboratory for the hydrolysis of lignocellulose with good cellulolytic activity when compared with other contemporary fungal strains. An attempt is made to sequence the cellobiohydrolases (CBHs) of A. fumigatus NITDGPKA3, model its structure to predict its catalytic activity towards improving the protein by genetic engineering approaches. Herein, the structure of the sequenced Cellobiohydrolases (CBHs) of A. fumigatus NITDGPKA3, modelled by homology modelling and its validation is reported. Further the catalytic activity of the modelled CBH enzyme was assessed by molecular docking analysis. Phylogenetic analysis showed that CBH from A. fumigatus NITDGPKA3 belongs to the Glycohydro 6 (Cel6A) super family. Molecular modeling and molecular dynamics simulation suggest the structural and functional mechanism of the enzyme. The structures of both the cellulose binding (CBD) and catalytic domain (CD) have been compared with most widely studied CBH of Trichoderma reesei. The molecular docking with cellulose suggests that Gln 248, Pro 287, Val236, Asn284, and Ala288 are the main amino acids involved in the hydrolysis of the β, 1-4, glycosidic bonds of cellulose.

A systems biology approach for elucidating the interaction of curcumin with Fanconi anemia FANC G protein and the key disease targets of leukemia

Abstract Fanconi anemia (FA) is an autosomal recessive disorder with a high risk of malignancies including acute myeloid leukemia and squamous cell carcinoma. There is a constant search out of new potential therapeutic molecule to combat this disorder. In most cases, patients with FA develop haematological malignancies with acute myeloid leukemia and acute lymphoblastic leukemia. Identifying drugs which can efficiently block the pathways of both these disorders can be an ideal and novel strategy to treat FA. The curcumin, a natural compound obtained from turmeric is an interesting therapeutic molecule as it has been reported in the literature to combat both FA as well as leukemia. However, its complete mechanism is not elucidated. Herein, a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia. The proteins namely DOT1L, farnesyl transferase (FDPS), histone decetylase (EP3000), Polo-like kinase (PLK-2), aurora-like kinase (AUKRB), tyrosine kinase (ABL1), and retinoic acid receptor alpha (RARA) were chosen as disease targets for leukemia and modeled structure of FANC G protein as the disease target for FA. The docking investigations showed that curcumin had a very high binding affinity of −8.1 kcal/mol with FANC G protein. The key disease targets of leukemia namely tyrosine kinase (ABL1), aurora-like kinase (AUKRB), and polo-like kinase (PLK-2) showed that they had the comparable binding affinities of −9.7 k cal/mol, −8.7 k cal/mol, and −8.6 k cal/mol, respectively with curcumin. Further, the percentage similarity scores obtained from PAM50 using EMBOSS MATCHER was shown to provide a clue to understand the structural relationships to an extent and to predict the binding affinity. This investigation shows that curcumin effectively interacts with the disease targets of both FA and leukemia.