Search

Aim: To develop novel compounds having potent anticancer and antibacterial activities. Background: Several studies have proved that benzylidene analogues of clinical 2,4-TZDs, such as troglitazone and ciglitazone, have more potent antiproliferative activity than their parent compounds. Literature studies also revealed that the attachment of more heterocyclic rings, containing nitrogen on 5th position of 2,4-TZD, can enhance the antimicrobial activity. Hence, attachment of various moieties on the benzylidene ring may produce safe and effective compounds in the future. Objective: The objective of the present study was to synthesize a set of novel benzylidene ring containing 5- and 3-substituted-2,4-thiazolidinedione derivatives and evaluate them for their anticancer and antibacterial activity. Methods: The synthesized compounds were characterized by IR, NMR, mass, and elemental studies. The in vitro cytotoxicity studies were performed for human breast cancer (MCF-7) and human lung cancer (A549) cells and HepG2 cell-line and compared to standard drug doxorubicin by MTT assay. Antimicrobial activity of the synthesized 2,4-thiazolidinediones derivatives was carried out using the cup plate method with slight modification. Results: The results obtained showed that TZ-5 and TZ-13 exhibited good antiproliferative activity against A549 cancer cell-line, whereas TZ-10 exhibited moderate antiproliferative activity against HepG2 cell-line when compared to standard drug doxorubicin. TZ-5 also exhibited reasonable activity against the MCF-7 cell-line with doxorubicin as standard. TZ-4, TZ-5, TZ-6, TZ-7, and TZ- 16 exhibited remarkable antibacterial activity against Gram positive and moderate activity against Gram negative bacteria with the standard drug ciprofloxacin. Conclusion: Attachment of heterocyclic rings containing nitrogen as the hetero atom improves the anticancer and antimicrobial potential. Attachment of electronegative elements like halogens can also enhance the antimicrobial activity. Further structure modifications may lead to the development of more potent 2,4-TZD leads that can be evaluated for further advanced studies. more...

Background: Piperine, a bioactive alkaloid was a well-known component which was used traditionally to treat a variety of disorders. Objective: The present review is to discuss the modified piperine or piperic acid analogs or its derivatives to explore the potential of piperine. Piperine or piperic acid had potentials as antibacterial, antitumor, antioxidant, anti-inflammatory, antifungal, immunomodulatory and many more for drug development. So modification in natural molecule piperine generates numerous derivatives or analogues which may be found beneficial in drug development. Methods: A literature survey has been carried out to determine the real potential of piperine and its modified analogs. Results: It has been scrutinized that piperine and its derivatives possess valuable components with good therapeutic potential. Conclusion: Thus, this review aims to provide knowledge as well as to explore the excellent potential of piperine, piperic acid, piperine derived compounds/ analogs which may further, after performing toxicity studies, and other parameters, be helpful in the design and development of novel drug candidates against numerous disease conditions and thus it paves way for further work in exploring the potential to treat the patients with obesity and skin related disorders. more...

Background: Piperine or piperic acid was isolated from fruits of Piper nigrum and had been reported as pharmacological valuable bioactive constituents. Keeping in view, a series of piperic acid-based N heterocyclic’s derivatives were synthesized and evaluated for antibacterial activity. All these prepared ligands were docked to study the molecular interactions and binding affinities against the protein PDB ID: 5 CDP. Objective: To meet the real need of newer antibacterials, we designed and synthesized scaffolds with good antibacterial activity. The obtained antibacterials have been validated in terms of ligand-protein interaction and thus prove to build up as good drug candidates. Methods: Antibacterial activity of the compounds were carried out against bacterial strains; three Grampositive and three Gram-negative bacterial strains using agar well diffusion method. In silico molecular docking studies were carried out using Glide (grid-based ligand docking) program incorporated in the Schrödinger molecular modeling package by Maestro 11.0. Results: Compounds BC 28, BC 32, and BC 33 exhibits antibacterial activity along with Glide docking score of -8.580, -9.753 kcal/mol, and -8.813 kcal/mol, respectively. Docking studies explained hydrogen bonding, pi-pi, and hydrophobic interactions with amino acid residues which explain the binding affinity of the most docked ligand with protein. Conclusion: In the present study, substituted piperic acid was synthesized and evaluated as antibacterial compared with standard drug ciprofloxacin and results interpret that having nitrogen as heteroatom in the heterocyclic nucleus found to be more potent than the standard drug ciprofloxacin. On comparing, substitution with electron-donating groups generates excellent antibacterial potential against the bacterial strains. It was also proved that having substitution with electron-donating groups on meta and para position with triazoline ring system exhibits greater potential while compounds which have a meta- electron-donating substituent showed lesser activity with thiazole nucleus. In addition, structure-based activities of the prepared analogs were discussed under Structure-Activity Relationship (SAR) section. more...

1,5-Benzodiazepines are considered some of the most vital classes of heterocyclic compounds due to their amazing biological and varied pharmacological activities. They are regarded as privileged structures and therefore have been striking synthetic targets for organic and medicinal chemists over the last decade. This results in the exploration of various silica supported catalysts, Lewis acids, organoacids, magnetic nanoparticles and other miscellaneous catalysts that have been investigated till date for an efficient and green synthesis of 1,5-benzodiazepine and its derivatives. The current review article primarily covers the one-pot green chemical synthesis of 1,5- benzodiazepines using various novel catalysts. The main motive of this review is the assessment of the literature on various catalysts along with their yield, reaction condition, and mechanism of action. In the end, the entire catalysts are structured systematically into various Lewis acids, Bronsted organoacids, supported catalysts, nanocatalysts, and miscellaneous catalysts and are presented in the form of tables for quick ‘at a glance’ study of catalysts, their reaction condition, time taken, etc. more...

Amidoalkyl-2-naphthol is one of the vital synthetic intermediates which occupy an imperative position in medicinal chemistry due to its amazing biological, pharmacological as well as industrial and synthetic applications. Owing to its diverse pharmaceutical activities, hundreds of scientific literature are available, signifying the efficient synthesis of this intermediate using various catalysts. Most of these literature methods suffer from low yield and harsh reaction conditions that further ignited the researcher to explore for another green catalyst and fresh methodologies. This review summarizes the last five years progress in the catalytic synthesis of 1-amidoalkyl-2-naphthols using various heterogenous, homogenous and nanocatalysts along with their mechanism of action. Various advantages like green synthesis, atom economy, clean reaction profile and catalyst recovery are discussed which facilitate the scientist to probe and stimulate the study on this scaffold. In the end, the catalysts and reactions condition are organized into the tables for swift at a glance understanding of different catalysts used with their yield and time taken for the synthesis. more...

Background: Many efforts have been explored in the last decade to treat colon cancer but nanoparticulate drug delivery systems are making a vital contribution in the improvement of drug delivery to colon cancer cells. Objective: In this review, we attempt to highlight recent advancements in the development of novel drug delivery systems of nanoparticles for the targeted drug delivery to colon. Polymers like Epithelial Cell Adhesion Molecule (EpCAM) aptamer chitosan, Hyaluronic Acid (HA), Chitosan (CS)– Carboxymethyl Starch (CMS), silsesquioxane capped mesoporous silica, Near IR (NIR) fluorescent Human Serum Albumin (HAS), poly(ethylene glycol)-conjugated hyaluronic acid etc. have been discussed by employing various anticancer drugs like doxorubicin, oxaliplatin, paclitaxel, 5-fluorouracil etc. Conclusion: These novel drug delivery systems have been determined to be more efficacious in terms of stability, sustained and targeted drug delivery, therapeutic efficacy, improved bioavailability and enhanced anticancer activity. more...

As a therapeutic group, non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used, prescribed and over the counter (OTC) medications for the treatment of inflammatory diseases, but suffering from several undesired side effects, the most important being ulcerogenicity, mucosal hemorrhage and gastritis. Most of the NSAID moieties are chemically composed of carboxylic functional groups and this could be one of the reasons for the damage to the mucosal lining. The prodrug designing is one of the several strategies used to overcome this drawback. Hence, in the last decade, the design and the synthesis of prodrugs of NSAIDs have been explored and given much attention by medicinal chemists. The rationale behind the prodrug concept is to achieve temporary blockade of the free carboxylic group present in the NSAIDs till their systemic absorption. This review is aimed to highlight and provide important information on NSAID prodrugs that have been designed and reported to be safe and more effective. This review will also focus on NSAID prodrugs that have been designed for improving therapeutic i.e. anti-inflammatory action as well as improving drug delivery at the target site. The most common derivatives of carboxylic NSAIDs that are discussed here belong to the chemical classes of esters, amides, anhydrides, acetals and the other derivatives with completely masked carboxylic groups. The successful prodrugs were listed and their molecular structures were also demonstrated here. The present review covers the recent updates present in literature and will surely provide a greater insight into the designing of safer NSAIDs in the future. more...

Background: Various mediators and anti-inflammatory drugs were used since from a long time but it is still a challenge for the medicinal chemists to treat or reduce the symptoms of inflammatory diseases. Most of the clinically used anti-inflammatory drugs such as NSAIDs, Coxibs and GCs are allied with considerable toxicity. Objective: The search of novel anti-inflammatory agent is not an ending process. Although the drug treatment has been improved steadily but yet, it is still there is a need to develop more potent therapeutic agents. Method: Reported literature survey has been studied to summarize the nitrogen containing moieties which were utilized as potential therapeutic agents. Results: A variety of N-heterocyclic analogs are known to exhibit a wide range of interesting biological activities like antioxidant, anti-inflammatory, anticonvulsant, analgesic, antimicrobial, anticancer, antiprotozoal, antioxidant, antiparasitic, antiplatelet, cardioprotective, anthelmintic, antidiabetic, antitubercular, trypanocidal and anti-HIV. However, numerous approaches were used to overcome the toxicity level such as co-administration with suitable agent/substance which provides protection against toxicity as well to synthesise new potent and safe anti-inflammatory drug. Conclusion: The present review summarizes the synthetic methodology and therapeutic potential of some N-heterocyclic analogs as potent anti-inflammatory agents. more...

Solid-state thermal neutron detectors are desired to replace 3He tube based technology for the detection of special nuclear materials. 3He tubes have some issues with stability, sensitivity to microphonics and very recently, a shortage of 3He. There are numerous solid-state approaches being investigated that utilize various architectures and material combinations. By using the combination of high-aspect-ratio silicon PIN pillars, which are 2 m wide with a 2 m separation, arranged in a square matrix, and surrounded by 10B, the neutron converter material, a high efficiency thermal neutron detector is possible. Besides intrinsic neutron detection efficiency, neutron to gamma discrimination is an important figure of merit for unambiguous signal identification. In this work, theoretical calculations and experimental measurements are conducted to determine the effect of structure design of pillar structured thermal neutron detectors including: intrinsic layer thickness, pillar height, substrate doping and incident gamma energy on neutron to gamma discrimination. more...

Interactions of surfactants with hydrophobically modified polyelectrolytes in aqueous solutions are important in several applications such as detergents, cosmetics, foods, and paints. Fundamental questions arise on the mechanisms of complexation of the polyelectrolyte and surfactant that control their behavior. In this work, the complexation was studied by examining interactions in aqueous solutions of a hydrophobically modified polymer, poly(maleic acid/octyl vinyl ether) (PMAOVE), with sodium dodecyl sulfate (SDS) by monitoring viscosity, pyrene solubility, light scattering, and analytical ultracentrifugation. When the anionic surfactant SDS was added to aqueous solutions of the similarly charged polymer PMAOVE, the surfactant was incorporated into the hydrophobic nanodomains of PMAOVE even far below the cmc of the surfactant. On the basis of viscosity, pyrene solubility, and analytical ultracentrifugation data, it is proposed that PMAOVE undergoes structural unfolding and at higher SDS concentrations mixed micelles are formed. more...

Abstract Chemical Vapour Deposition (CVD) of cobalt was deposited from a liquid source precursor of cobalt tricarbonyl nitrosyl (Co(CO)3NO) on to oxidised < 100 > silicon wafers. The cobalt layers were deposited at 450∘C at 1.5 torr chamber pressure of hydrogen for 15 min processing time with various precursor flow rates. X-ray diffraction studies of the cobalt films reveal both hcp and fcc peaks. The vibrating sample magnetometer (VSM) yields coercivity (Hc) 167 Oe and 364 Oe for 46 nm and 30 nm thickness layers respectively at room temperature and squareness (S) Mr/Ms (remanence/saturation of magnetisation) value of  1. The study of magnetic properties of the cobalt suggests that magnetisation is dependent on grain size and therefore thickness. The grain size was observed by atomic force microscopy (AFM). Magnetic images were observed by magnetic force microscopy (MFM) and analyzed in terms of domain structure. The surface domain structure was recorded with the tip lift height 100 nm so that the magnetic interactions arising produced the topography effect. Where there is repulsive interaction the intensity is recorded as a bright region and where the interaction is attractive the intensity is recorded as a dark region. more...

The mechanism of vesicle-to-micelle transformation due to the interactions with sodium dodecylsulfate (SDS) has been studied by monitoring changes in the optical density, surface tension, SDS monomer concentrations, pyrene fluorescence, and mass spectrometry. Two inflection points appeared on the optical density as well as effective hydrodynamic diameter curves. Based on the results of the surface tension and SDS monomer measurements, the first inflection point is attributed to the saturation of bilayers by SDS monomers and the onset of liposome solubilization processes. The second inflection point corresponds to the onset of complete disruption of bilayers and the critical micelle concentration of the mixed systems. The fluorescence results show the core of the mixed micelles to be more hydrophobic than that of the SDS micelles, suggesting that liposome solubilization is a micellization process. From the individual phospholipid liposome solubilization studies, it was found that phosphatidic acid (PA) molecules are more susceptible toward SDS. Interestingly, it has been detected from the mass spectra that the disruption of liposome bilayers is a preferential dissolution process. It is proposed that, at low SDS concentration, PA molecules preferentially exit first from the mixed liposome bilayers (1:1 PA/phosphatidylcholine), causing liposome solubilization. In contrast, at high SDS concentrations, the breakdown of liposome takes place instantaneously. more...

Interactions between sodium dodecyl sulfate and zein protein, a model system for the understanding of the effect of surfactants on skin, were investigated using a range of techniques involving UV−vis spectroscopy, TOC (total organic carbon analysis), electrophoresis, and static and dynamic light scattering. Zein protein was solubilized by SDS. The adsorption of SDS onto insoluble protein fraction caused the zeta potential of the complex to become more negative. From these values, we calculated the Gibbs energy of absorption, which decreases when the SDS concentration is raised. Finally the structure of the complex, based on the analysis by static and dynamic light scattering, is proposed to be rod like. more...

It is well-known that harshness and skin irritation are related to surfactant−skin lipid interactions. Delipidization of the stratum corneum is caused by surfactant penetration into extracellular lipid bilayers, disrupting the lipid microstructure and, thereby, impairing skin-barrier properties. The main objective of this work was to investigate the mechanisms of interactions of sodium dodecyl sulfate (SDS) with liposomes as model membranes. Vesicle-to-micelle structural transitions that occur as a result of the interaction of SDS with liposomes (1:1 phosphatidylcholine/phosphatidic acid) were studied by monitoring the optical density, surface tension, and monomer concentration. Two inflections appeared on the turbidity curve, which allowed the determination of surfactant concentrations corresponding to the onset and completion of the solubilization of liposomes. The effective surfactant-to-lipid mole ratios in the surfactant-saturated lipid bilayers (R^sat) and in the lipid-saturated mixed micelle (R^sol) were estimated from the excess surfactant monomer left in the supernatant. The monomer concentration of the surfactant in the supernatant of the liposome/surfactant suspension was estimated by ultrafiltration followed by a titration technique. The changes in the surface-tension data enabled us to elucidate the mechanisms by which surfactant solubilizes the liposomes and finally reaches the critical micelle concentration of mixed micelles at the end of the solubilization process. more...

Interactions of a model surfactant, sodium dodecyl sulfate (SDS), with a water-insoluble model protein, zein, were investigated to gain an understanding of the effects, such as skin irritation and protein denaturation, of surfactants that are common in personal-care products. To elucidate the mechanisms of such effects, the zein protein interaction with SDS in aqueous solutions was investigated using a multipronged approach involving a range of techniques, such as UV−visible and fluorescence spectroscopy, TOC (total organic carbon analysis), light scattering, and viscosimetry. The zein protein solubilization increases with an increase in the SDS concentration. Solubilization of zein occurs in two distinct stages followed by a complete unfolding of the protein. In the first stage ([SDS] ~ 4 mM; critical complexation concentration), SDS is incorporated into the globular zein structure, forming small hydrophobic microdomains. From the pyrene fluorescence lifetime decay measurements, the aggregation number of SDS in such hydrophobic microdomains was found to be markedly lower than the aggregation number of pure SDS micelles in the bulk solution. The vibrational fine structure of pyrene fluorescence, however, showed the core of SDS−zein complex micelles to be more hydrophobic than that of the SDS micelles. In the second stage ([SDS] ~ 200 mM; unfolding concentration), the protein unfolds, as is evidenced by viscosity and dynamic light scattering measurements. more...

Biological membranes are formed from the supramolecular aggregates of lipids, cholesterols, proteins, and other components such as carbohydrates. Harshness of personal cleaning products is related to surfactant interactions with proteins and lipids. Surfactants can damage biomembranes either by solubilizing their components in surfactant micelles or by fluidizing lipid bilayers through surfactant penetration. The interactions of surfactants with simpler biomembranes such as phosphatidic acid and phosphatidyl choline liposomes were first studied (Deo, N.; Somasundaran, P. Colloids Surf., A 2001, 186, 33), and then cholesterol and zein protein were added to make the liposomes more realistic. Sodium dodecyl sulfate (SDS) was used as a model surfactant for this purpose. Results show that while cholesterol makes the liposomes more resistant toward SDS, protein enhances the liposome solubilization processes. The mechanisms of the above process were investigated using a multipronged approach involving UV−visible spectroscopy, viscometry, and analytical ultracentrifugation. From viscometry and analytical ultracentrifuge analysis, it was seen that protein undergoes structural reorientation in the presence of SDS due to its strong affinity toward SDS, which stimulates the zein protein to be extracted away first from the bilayers. The preferential exits of zein protein out of the liposome membrane perturb the stability of the liposomes and enhance the liposome disintegration process. more...

This paper summarizes some work that I have been doing on eigenvalue correlators of random matrix models which show some interesting behavior. First we consider matrix models with gaps in their spectrum or density of eigenvalues. The density-density correlators of these models depend on whether N, where Nis the size of the matrix, takes even or odd values. The fact that this dependence persists in the large Nthermodynamic limit is an unusual property and may have consequences in the study of one electron effects in mesoscopic systems. Secondly, we study the parametric and cross correlators of the Harish Chandra-Itzykson-Zuber matrix model. The analytic expressions determine how the correlators change as a parameter (e.g. the strength of a perturbation in the Hamiltonian of the chaotic system or external magnetic field on a sample of material) is varied. The results are relevant for the conductance fluctuations in disordered mesoscopic systems. more...

We present an optimal parallel algorithm for the construction of (a, b)-trees-a generalization of 2-3 trees, 2-3-4 trees, and B-trees. We show the existence of a canonical form for (a, b)-trees, with a very regular structure, which allows us to obtain a scalable parallel algorithm for the construction of a minimum-height (a, b)-tree with Nkeys in O(N/p+ log log N) time using p≤ N/log log Nprocessors on the EREW-PRAM model, and in O(N/p) time using p≤ Nprocessors on the CREW model. We show that the average memory utilization for the canonical form is at least 50% better than that for the worst-case and is also better than that for a random (a, b)-tree. A significant feature of the proposed parallel algorithm is that its time-complexity depends neither on anor on b, and hence our general algorithm is superior to earlier algorithms for parallel construction of B-trees. more...

We present several parallel algorithms for the problem of finding shortest paths from a specified vertex (called the source) to all others in a weighted directed graph. The algorithms are for machines ranging from array processors, multipleinstruction multiple-data stream machines to a special network of processors. These algorithms have been designed by “parallelizing” two classic sequential algorithms — one due to Dijkstra (1959), the other due to Moore (1957). Our interest is not only in obtaining speeded-up parallel versions of the algorithms but also in exploring the design principles, the commonality of correctness proofs of the different versions, and the subjective complexity of explaining and understanding these versions. more...

Solid-state thermal neutron detectors are desired to replace 3He tube tube-based technology for the detection of special nuclear materials. 3He tubes have some issues with stability, sensitivity to microphonics and very recently, a shortage of 3He. There are numerous solid-state approaches being investigated that utilize various architectures and material combinations. Our approach is based on the combination of high-aspect-ratio silicon PIN pillars, which are 2 m wide with a 2 m separation, arranged in a square matrix, and surrounded by 10B, the neutron converter material. To date, our highest efficiency is ~ 20 % for a pillar height of 26 m. An efficiency of greater than 50 % is predicted for our device, while maintaining high gamma rejection and low power operation once adequate device scaling is carried out. Estimated required pillar height to meet this goal is ~ 50 m. The fabrication challenges related to 10B deposition and etching as well as planarization of the three-dimensional structure is discussed. more...

Pseudoephedrine (I) is N‐alkylated with the chlorides (II) in the presence of a base to give the derivatives (III).