Sumit Kumar Pramanik

Dipeptide derived from benzylcystine forms unbranched nanotubes in aqueous solution

The essence of modern nanotechnology is manifested in the formation of well-ordered nanostructures by a process of self-association. Peptides are among the most useful building blocks for organic bionanostructures such as nanotubes, nanospheres, nanotapes, nanofibrils, and other different ordered structures at the nanoscale. Peptides are biocompatible, chemically diverse, and much more stable and can be readily synthesized on a large scale. Also, they have diverse application in biosensors, tissue engineering, drug delivery, etc. Here, we report a short cystine-based dipeptide, which spontaneously self-associates to form straight, unbranched nanotubes. Such self-assembled nanobiomaterials provide a novel possibility of designing new functional biomaterials with potential applications in nanobiotechnology. The formation of nanotubes in solution state has been demonstrated by atomic force microscopy and scanning electron microscopy. Infrared absorption and circular dichroism demonstrated the intermolecular β-sheet-like backbone hydrogen bonding in juxtaposing and stacking of aromatic side chains.

Synthesis, characterization and cytotoxicity study of magnetic (Fe3O4) nanoparticles and their drug conjugate

An easy synthesis of magnetic nanoparticles (Fe3O4) is described. Transmission electron microscopy (TEM), atomic force microscopy (AFM), dynamic light scattering (DLS) and X-ray diffraction (XRD) have been used to study the well dispersed and uniformly spherical nanoparticles. 5-Fluorouracil (5-FU) has been successfully loaded onto the nanoparticles and cytotoxicity studies were performed using a standard MTT assay. The results indicate that 5-fluorouracil-loaded iron nanoparticles are a more potent anticancer drugversus5-fluorouracil alone.

Efficacy of Cyclin Dependent Kinase 4 Inhibitors as Potent Neuroprotective Agents against Insults Relevant to Alzheimer’s Disease

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with no cure till today. Aberrant activation of cell cycle regulatory proteins is implicated in neurodegenerative diseases including AD. We and others have shown that Cyclin dependent kinase 4 (Cdk4) is activated in AD brain and is required for neuron death. In this study, we tested the efficiency of commercially available Cdk4 specific inhibitors as well as a small library of synthetic molecule inhibitors targeting Cdk4 as neuroprotective agents in cellular models of neuron death. We found that several of these inhibitors significantly protected neuronal cells against death induced by nerve growth factor (NGF) deprivation and oligomeric beta amyloid (Aβ) that are implicated in AD. These neuroprotective agents inhibit specifically Cdk4 kinase activity, loss of mitochondrial integrity, induction of pro-apoptotic protein Bim and caspase3 activation in response to NGF deprivation. The efficacies of commercial and synthesized inhibitors are comparable. The synthesized molecules are either phenanthrene based or naphthalene based and they are synthesized by using Pschorr reaction and Buchwald coupling respectively as one of the key steps. A number of molecules of both kinds block neurodegeneration effectively. Therefore, we propose that Cdk4 inhibition would be a therapeutic choice for ameliorating neurodegeneration in AD and these synthetic Cdk4 inhibitors could lead to development of effective drugs for AD.

Potent anticancer activity of cystine-based dipeptides and their interaction with serum albumins

BackgroundCancer is a severe threat to the human society. In the scientific community worldwide cancer remains a big challenge as there are no remedies as of now. Cancer is quite complicated as it involves multiple signalling pathways and it may be caused by genetic disorders. Various natural products and synthetic molecules have been designed to prevent cell proliferation. Peptide-based anticancer drugs, however, are not explored properly. Though peptides have their inherent proteolytic instability, they could act as anticancer agents.ResultsIn this present communication a suitably protected cystine based dipeptide and its deprotected form have been synthesized. Potent anticancer activities were confirmed by MTT assay (a laboratory test and a standard colorimetric assay, which measures changes in colour, for measuring cellular proliferation and phase contrast images. The IC50 value, a measure of the effectiveness of a compound in inhibiting biological or biochemical function, of these compounds ranges in the sub-micromolar level. The binding interactions with serum albumins (HSA and BSA) were performed with all these molecules and all of them show very strong binding at sub-micromolar concentration.ConclusionsThis study suggested that the cystine-based dipeptides were potential anticancer agents. These peptides also showed very good binding with major carrier proteins of blood, the serum albumins. We are currently working on determining the detailed mechanism of anticancer activity of these molecules.

Synthesis and Cytotoxicity Studies of Novel Triazolo-Benzoxazepine as New Anticancer Agents

Cancer continues to be one of the biggest threats to the human civilization because there is no cure of it. Small heterocyclic molecule with low molecular weight and novel structural feature is therapeutically highly demanding. These molecules have the capability to disrupt signaling pathways leading to anticancer activities. Therefore, the search for new anticancer agents continues to draw attention to the research community. In this study, a small triazolo‐benzoxazepine scaffolds was synthesized using a one‐pot four‐step synthetic methodology involving click reaction. Small libraries of 12 compounds were successfully synthesized and screened them against different cancer cell lines. Low micromolar anticancer activity was recorded using MTT assay, and further confirmation of cell death was obtained by phase contrast, fluorescent, and confocal images.

Conformation and cytotoxicity of a tetrapeptide constellated with alternative D- and L-proline

Proline containing peptides are highly important due to their natural abundance in various secondary structural elements like turns (β turn and γ turn etc.) in proteins. Here the conformation, cytotoxicity and structure of a unique tetrapeptide composed of alternative D- and L-proline residues are discussed. The peptide showed a polyproline II like conformation in dilute aqueous solution. The aqueous solution of the peptide self-assembled to form spheroidal oligomers with a diameter of ∼90 nm. The morphological features were confirmed by bright field confocal images, TEM analysis and AFM. The alternative D- and L-proline residues in the peptide showed toxicity towards cancer cell lines and ∼50% cell death was recorded against three different types of cancer cells (Neura 2a, HEK 293 and Hep G2).

Binding of hemoglobin to ultrafine carbon nanoparticles: a spectroscopic insight into a major health hazard

Carbon nanoparticles (CNPs) are light and easily absorb into different parts of organs of the human body. They are suspended particulate matters of respirable sizes. In the atmosphere, ultrafine CNPs are known to be generated mainly from the combustion of fuels and have been reported to be a major contributor to the induction of cardiopulmonary diseases. In third world countries, these diseases are more prevalent because of the higher abundance of ultrafine CNPs in the air. Different nanostructured materials, when exposed to the human body, can easily enter into the body through the lungs or other organs and tissues. In the laboratory, ultrafine carbon nanoparticles were synthesized and their structure was confirmed by DLS experiments, TEM and AFM imaging studies. Their interactions with hemoglobin (Hb) and myoglobin (Mb) were studied using fluorescence spectroscopy. The results indicate a remarkably strong interaction between carbon nanoparticles and Hb (or Mb). Temperature dependent steady state fluorescence spectroscopy showed exothermic binding of Hb to CNPs, which is favored by enthalpy and entropy changes. A circular dichroism study also indicated significant change in the protein secondary structure and a partial unfolding of the helical conformation. These findings are highly important for understanding the interactions between CNPs and Hb (or Mb), which might help to better clarify the potential risks and undesirable health hazards associated with carbon nanoparticles.

Silver-catalysed azide-alkyne cycloaddition (AgAAC): assessing the mechanism by density functional theory calculations.

‘Click reactions’ are the copper catalysed dipolar cycloaddition reaction of azides and alkynes to incorporate nitrogens into a cyclic hydrocarbon scaffold forming a triazole ring. Owing to its efficiency and versatility, this reaction and the products, triazole-containing heterocycles, have immense importance in medicinal chemistry. Copper is the only known catalyst to carry out this reaction, the mechanism of which remains unclear. We report here that the ‘click reactions’ can also be catalysed by silver halides in non-aqueous medium. It constitutes an alternative to the well-known CuAAC click reaction. The yield of the reaction varies on the type of counter ion present in the silver salt. This reaction exhibits significant features, such as high regioselectivity, mild reaction conditions, easy availability of substrates and reasonably good yields. In this communication, the findings of a new catalyst along with the effect of solvent and counter ions will help to decipher the still obscure mechanism of this important reaction.

Binding studies of creatinine and urea on iron-nanoparticle

Abstract Kidney diseases are complicated and can be fatal. Dialysis and transplantation are the only survival solutions to the patients suffering from kidney failures. Both hemodialysis and peritoneal dialysis are risky, due to the possibility of infection and these are expensive and time consuming. The development of simple and reliable technique for the clearance of creatinine and urea from the body is an important part of biotechnology. We have synthesized an iron nanoparticle (INP) and studied its binding with creatinine and urea. The DLS, TEM, AFM, FT-IR and Powder-XRD studies demonstrate strong binding of creatinine and urea to the nanoparticles. This finding may be helpful if it is used in the dialysis technologies. The proposed method may substantially decrease dialysis time and improve its quality in terms of urea and creatinine clearances.

Synthesis and cytotoxicity studies of 1-propenyl-1,3-dihydro-benzimidazol-2-one

A heterocyclic compound 1-propenyl-1,3-dihydro-benzimidazol-2-one was synthesized by a palladium-catalyzed rearrangement reaction. Anticancer activities were confirmed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay against Neura 2a (neuroblastoma cell), HEK 293 (kidney cancer) and MCF-7 (breast cancer) cell lines at low micromolar range. Furthermore, clear images from phase-contrast and fluorescence microscopes and confocal images unambiguously confirm the cancer cell death. The single X-ray crystal structure of the compound unambiguously proves the structure of the benzimidazolone compound.