A poly(acrylic acid)-modified copper-organic framework for electrochemical determination of vancomycin.

A copper(II) benzene-1,3,5-tricarboxylate (BTC) metal-organic framework (MOF) was modified with poly(acrylic acid) (PAA) and then used in an electrochemical sensor for vancomycin. The MOF, synthesized via a single-pot method, has enhanced solubility and dispersibility in water as compared to HKUST-1 but without compromising its crystallinity and porosity. The MOF was placed on a glassy carbon electrode (GCE) where it shows enhanced electrocatalytic properties. This is assumed to be due to the presence of the poly(acrylic acid) that forms a network between various HKUST-1 crystals through dimer formation between the carboxy groups of BTC and PAA. This also led to better dispersion of the MOF and to improved interaction between MOF and vancomycin. The structural, spectral and electrochemical properties of the MOFs and their vancomycin complexes was characterized. The modified GCE is shown to be a viable tool for electrochemical determination (best at a working potential of 784 mV vs. Ag/AgCl) of the antibiotic vancomycin in spiked urine and serum samples. Response is linear in the 1-500 nM vancomycin concentration range, and the detection limit is 1 nM, with a relative standard deviation of ±4.3%. Graphical abstractSchematic representation of a method for determination of vancomycin. Poly(acrylic acid) modified HKUST-1 (P-HKUST-1) forms a complex with vancomycin [Van-P-HKUST-1] which is coated over glassy carbon electrode (GCE). The decrease in peak current is recorded as response to vancomycin via cyclic voltammetry.

Nanomaterial-based optical and electrochemical techniques for detection of methicillin-resistant Staphylococcus aureus: a review.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for a number of life-threatening complications in humans. Mutations in the genetic sequence of S. aureus due to the presence of certain genes results in resistance against ß-lactamases. Thus, there is an urgent need for developing highly sensitive techniques for the early detection of MRSA to counter the rise in resistant strains. This review (142 refs.) extensively covers literature reports on nanomaterial-based optical and electrochemical sensors from the year 1983 to date, with particularly emphasis on recent advances in electrochemical sensing (such as voltammetry and impedimetric) and optical sensing (such as colorimetry and fluorometry) techniques. Among the electrochemical methods, various nanomaterials were employed for the modification of electrodes. Whereas, in optical assays, formats such as enzyme linked immunosorbent assay, lateral flow assays or in optical fiber systems are common. In addition, novel sensing platforms are reported by applying advanced nanomaterials which include gold nanoparticles, nanotitania, graphene, graphene-oxide, cadmium telluride and related quantum dots, nanocomposites, upconversion nanoparticles and bacteriophages. Finally, closing remarks and an outlook conclude the review. Graphical abstract Schematic of the diversity of nanomaterial-based methods for detection of methicillin-resistant Staphylococcus aureus (MRSA). AuNPs: gold nanoparticles; QDs: quantum dots; PVL: Panton-Valentine leukocidin; mecA gene: mec-gene complex encoding methicillin resistance.

Structural insight of glitazone for hepato-toxicity: Resolving mystery by PASS.

Troglitazone causes severe hepatic injury in certain individuals and multiple mechanisms related to hepato-toxicity has been reported creating confusion. In the present study, the mechanism for the hepatic injury of glitazones was investigated by PASS. The results suggest that chromane containing glitazones are apoptic agonist (activating p53 by intrinsic pathway leading to the apoptosis) and those which do not contain the chromane are devoid of this. In case of hepato-toxicity by non-chromane glitazone and their metabolite such as M-3, RM-3, rosiglitazone and pioglitazone; PASS suggest that these chemicals are not apoptic agonist but they are the substrate for CYP enzyme (Phase-I Oxidative Enzyme) and Phase-II conjugating enzymes; interfering with bile acid metabolism rendering bile acid more toxic (cholestasis). This unmetabolised bile salt further initiates the process apoptosis via intrinsic and extrinsic pathway leading to the apoptosis. Immunoblot analysis further confirm our hypothesis that troglitazone (chromane containing glitazone), but not rosiglitazone and pioglitazone (non-chromane containing glitazone) increased the levels of p53 in a time-dependent manner. Hence our prediction related to the mechanism of hepato-toxicity by apoptosis and structural insight of glitazone can be helpful in improving the drug profile of this category.

One pot fabrication of diamino naphthalene -AuNPs decorated graphene nanoplatform for the MRSA detection in the biological sample.

Early monitoring of MRSA can effectively mitigate the disease risk by using Penicillin-binding protein 2a (PbP2a) biomarker. Diamino naphthalene-AuNPs decorated graphene (AuNPsGO-DN) nanocomposite was synthesized for a rapid and sensitive immunosensor detecting PbP2a. The synthesized AuNPsGO-DN nanocomposites were characterized by field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (SEM-EDX), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, and X-ray diffraction spectroscopy (XRD). Electrochemical characterization done with cyclic voltammetry (CV), differential pulse voltammetry (DPV), and electrical impedance spectroscopy (EIS) techniques. Anti-PbP2a monoclonal antibodies immobilized at AuNPsGO-DN/GCE via covalent bonding. AuNPs enhanced the electrode surface area and the antibodies' loading. Mercaptopropionic acid (MPA) was a linker between the AuNPs and antibodies, orientated the antibodies as opposite to the PbP2a antigen, and improved the sensitivity and specificity. The antiPbP2a/MPA/AuNPsGO-DN/GCE electrode displayed sensitive and selective detection towards the PbP2a antigen in phosphate buffer saline (PBS pH 7.4). The broad linear range from 0.01 to 8000 pg/mL was obtained with LOD of 0.154 pg/mL and 0.0239 pg/mL, respectively. A label-free, simple, and sensitive immunosensor was developed with a 98-106 % recovery rate in spiked biological samples. It shows the potential applicability of the developed immunoelectrode.

One-pot synthesis of ß-cyclodextrin modified silver nanoparticles for highly sensitive detection of ciprofloxacin.

This study emphases on electrochemical detection of ciprofloxacin in sheep serum and runoff water using silver nanoparticle modified ß-cyclodextrin (Ag-ß-CD) composite. The Ag-ß-CD composite was synthesized via a hydrothermal route, which resulted in a high product yield. Morphological and spectral characterizations of the Ag-ß-CD composite were carried out. The Ag-ß-CD composite was used to detect ciprofloxacin by employing differential pulse voltammetry (DPV) and cyclic voltammetry (CV). The Ag-ß-CD modified electrode displayed excellent specificity towards the electro-oxidation of ciprofloxacin. Further, the sensor gave the best response towards the electro-oxidation of ciprofloxacin near the human physiological pH of 7.5. A linear response was obtained between the concentration range of 0.1 nM to 50 nM and the limit of detection (LOD) at 0.028 nM with high sensitivity and selectivity towards ciprofloxacin oxidation. The current work has a rationally synthesized and characterized nanocomposite with a very high potential for rapid and sensitive detection of ciprofloxacin in spiked sheep blood serum and domestic runoff water samples. High sensitivity and low LOD results illustrate good practicability for the detection of ciprofloxacin in such samples in the near future.

A highly dispersed multi-walled carbon nanotubes and poly(methyl orange) based electrochemical sensor for the determination of an anti-malarial drug: Amodiaquine.

A glassy carbon electrode modified with electrochemically polymerized methyl orange (PMO) and multi-walled carbon nanotubes (MWCNT) was developed. The morphologies of the fabricating materials (PMO and MWCNT) were investigated by field-emission scanning electron microscopy (FE-SEM). The designed sensor was used for the sensitive determination of amodiaquine (AQ), an anti-malaria drug. AQ was developed as an alternative to chloroquine because of its activity against chloroquine-resistant Plasmodium falciparum (P. falciparum) parasites. The modified electrode was employed to study the electrochemical oxidation of AQ using cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. Under optimal experimental conditions, DPV exhibited a linear response in the concentration range from 1.0 × 10-7 to 3.5 × 10-6 mol L-1 with a limit of detection (LOD) of 8.9 × 10-8 mol L-1. Furthermore, the number of electrons and protons involved in the electrochemical study of AQ was also calculated and a plausible mechanism for the electro-oxidation of AQ was deduced. The developed sensor demonstrated analytical applicability as it was successfully employed to determine the drug AQ in pharmaceutical formulations and human urine samples.

Conducting polymer-based electrochemical biosensors for neurotransmitters: A review.

Neurotransmitters are important biochemical molecules that control behavioral and physiological functions in central and peripheral nervous system. Therefore, the analysis of neurotransmitters in biological samples has a great clinical and pharmaceutical importance. To date, various methods have been developed for their assay. Of the various methods, the electrochemical sensors demonstrated the potential of being robust, selective, sensitive, and real time measurements. Recently, conducting polymers (CPs) and their composites have been widely employed in the fabrication of various electrochemical sensors for the determination of neurotransmitters. Hence, this review presents a brief introduction to the electrochemical biosensors, with the detailed discussion on recent trends in the development and applications of electrochemical neurotransmitter sensors based on CPs and their composites. The review covers the sensing principle of prime neurotransmitters, including glutamate, aspartate, tyrosine, epinephrine, norepinephrine, dopamine, serotonin, histamine, choline, acetylcholine, nitrogen monoxide, and hydrogen sulfide. In addition, the combination with other analytical techniques was also highlighted. Detection challenges and future prospective of the neurotransmitter sensors were discussed for the development of biomedical and healthcare applications.

Fabrication of highly sensitive gold nanourchins based electrochemical sensor for nanomolar determination of primaquine.

A gold nanourchins modified glassy carbon electrode (AuNu/GCE) was developed for the determination of antimalarial drug, primaquine (PQ). The surface of AuNu/GCE was characterized by electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and cyclic voltammetry (CV). EIS results indicated that the electron transfer process at AuNu/GCE was faster as compared to the bare electrode. The SEM and TEM image confirmed the presence and uniform dispersion of gold nanourchins on the GCE surface. Upon investigating the electrochemical behavior of PQ at AuNu/GCE, the developed sensor was found to exhibit high electrocatalytic activity towards the oxidation of PQ. Under optimal experimental conditions, the sensor showed fast and sensitive current response to PQ over a linear concentration range of 0.01-1µM and 0.001-1µM with a detection limit of 3.5nM and 0.9nM using differential pulse voltammetry (DPV) and square wave voltammetry (SWV), respectively. The AuNu/GCE showed good selectivity, reproducibility and stability. Further, the developed sensor was successfully applied to determine the drug in human urine samples and pharmaceutical formulations demonstrating its analytical applicability in clinical analysis as well as quality control. The proposed method thus provides a promising alternative in routine sensing of PQ as well as promotes the application of gold nanourchins in electrochemical sensors.

Electrochemically reduced graphene oxide/Poly-Glycine composite modified electrode for sensitive determination of l-dopa.

A facile preparation strategy based on electrochemical technique for the fabrication of glycine (Poly-Gly) and electrochemically reduced graphene oxide (ERGO) composite modified electrode was developed. The morphology of the developed composite (ERGO/Poly-Gly) was investigated using field emission scanning electron microscope (FE-SEM). The composite modified glassy carbon electrode (GCE) was characterized using fourier transform-infrared (FT-IR) spectroscopy, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The electrochemical characterization results revealed that ERGO/Poly-Gly modified GCE has excellent electrocatalytic activity. Further, it was employed for sensing of l-dopa in pH5.5. Differential pulse voltammetry (DPV) was used for the quantification of l-dopa as well as for the simultaneous resolution of l-dopa and uric acid (UA). The LOD (S/N=3) was found to be 0.15µM at the proposed composite modified electrode. Determination of l-dopa could also be achieved in the presence of potentially interfering substances. The sensor showed high sensitivity and selectivity with appreciable reliability and precision. The proposed sensor was also successfully applied for real sample analysis.

An insight on synthetic and medicinal aspects of pyrazolo[1,5-a]pyrimidine scaffold.

Pyrazolo[1,5-a]pyrimidine scaffold is one of the privileged hetrocycles in drug discovery. Its application as a buliding block for developing drug-like candidates has displayed broad range of medicinal properties such as anticancer, CNS agents, anti-infectious, anti-inflammatory, CRF1 antagonists and radio diagnostics. The structure-activity relationship (SAR) studies have acquired greater attention amid medicinal chemists, and many of the lead compounds were derived for various disease targets. However, there is plenty of room for the medicinal chemists to further exploit this privileged scaffold in developing potential drug candidates. The present review briefly outlines relevant synthetic strategies employed for pyrazolo[1,5-a]pyrimidine derivatives. It also extensively reveals significant biological properties along with SAR studies. To the best of our understanding current review is the first attempt made towards the compilation of significant advances made on pyrazolo[1,5-a]pyrimidines reported since 1980s.

Electroanalysis of antitubercular drugs in pharmaceutical dosage forms and biological fluids: a review.

Tuberculosis remains a major global public health problem. Given the need for extensive analysis of antitubercular drugs, the development of sensitive, reliable and facile analytical methods to determine these compounds becomes necessary. Electrochemical techniques have inherent advantages over other well-established analytical methods, this review aiming to provide an updated overview of the latest trends (from 2006 till date) in the voltammetric determination of antitubercular drugs. Furthermore, the advantages and limitations of these methods are critically discussed. The review reveals that in spite of using a variety of chemically modified electrodes to determine antitubercular drugs, there is still a dearth of applicability of the voltammetric methods to quantify these compounds in human body fluids, especially in blood plasma.

A categorical review on electroanalytical determination of non-narcotic over-the-counter abused antitussive drugs.

Dextromethorphan (DXM) and diphenhydramine (DPH) are two commonly used over-the-counter non-narcotic antitussive drugs. Recent reports reveal the widespread abuse of DXM and DPH due to their euphoric and alcohol-like effects. Due to their medicinal importance as well as the apparent increase in their use as abused drugs, it has become critical to determine them in samples of biological, clinical and pharmaceutical interest. The electrochemical techniques for drug analysis have gathered considerable attention due to their pronounced selectivity, sensitivity and simplicity. The given review presents a compilation of published voltammetric and potentiometric methods developed for determination of DXM and DPH. It critically highlights the analytical performances, revealing the recent trends and progress in the specified approach for their analysis. The review forms a basis for further progress in this field and development of improved electrochemical sensors to determine the drug.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors from the natural origin: a recent perspective.

Overexpression of epidermal growth factor receptor (EGFR) is seen in a number of human tumors like prostate, colon, breast and ovarian. Their expression is correlated with vascularity and often difficult to diagnose. Though a number of active inhibitors and anticancer drugs against EGFR-tyrosine kinase are known, increase in resistance together with many side effects designate the need for new and improved treatments. Natural products and their analoges have significant contribution in the cancer drug discovery and development process. Therefore in the current review we mainly discuss design, synthesis and structural activity relationship of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors from the natural origin.

An insight into purine, tyrosine and tryptophan derived marine antineoplastic alkaloids.

There is an ever-increasing need for the development of new drugs with safe and improved profile for the treatment of cancer. From time immemorial, nature has been considered as an abundant source of medicinal compounds having therapeutic properties. An enormous chemical diversity is present in thousands and millions of species of microorganisms, marine organisms, plants and animals that can act as potential therapeutic agents against various types of human cancer. Literature survey revealed that many alkaloids isolated from marine cyanobacteria, fungi, algae, sponges and tunicates displayed a wide range of anticancer properties like antiproliferative, antiangiogenic, induction of apoptosis, promoting cytotoxicity by inhibition of topoisomerase activities and tubulin polymerization. In this context, bastadins derived from tyrosine-based alkaloids have been reported as one the important class of anticancer agents. In particular bastadin 6 (24), seems to be a promising natural lead compound for the development of marine natural product-based anticancer therapeutic agents. This review mainly highlights the pharmacologically active scaffolds like purine, tyrosine and tryptophan containing marine alkaloids that exhibit biological activity, including anti-angiogenesis, cytotoxicity and anticancer activity.

Current perspective of natural alkaloid carbazole and its derivatives as antitumor agents.

Throughout our evolution, the importance of natural products for medicine and health has been increasing and it continues to be a key source of novel anticancer drugs, leads and new chemical entities. Among natural products, tricyclic heteroaromatic alkaloids such as carbazoles are an important class of natural and semi-synthetic organic compounds. In the last few decades medicinal role of natural and semi-synthetic carbazoles has expanded significantly, especially as a vital heterocyclic class of antitumor agents. Some of the carbazoles that displayed potential anticancer activity have undergone clinical trials. However, complications arising due to multidrug resistance in clinical trials led to very few of the selected carbazoles being approved for cancer therapy. Planar, polycyclic and aromatic carbazoles exhibit anticancer activity via DNA intercalation. Further many carbazoles can be cytotoxic by inhibiting DNA-dependent enzymes such as telomerase and topoisomerase I/II.