Neuropharmacological potential of honokiol and its derivatives from Chinese herb Magnolia species: understandings from therapeutic viewpoint.

Honokiol is a neolignan biphenol found in aerial parts of the Magnolia plant species. The Magnolia plant species traditionally belong to China and have been used for centuries to treat many pathological conditions. Honokiol mitigates the severity of several pathological conditions and has the potential to work as an anti-inflammatory, anti-angiogenic, anticancer, antioxidant, and neurotherapeutic agent. It has a long history of being employed in the healthcare practices of Southeast Asia, but in recent years, a greater scope of research has been conducted on it. Plenty of experimental evidence suggests it could be beneficial as a neuroprotective bioactive molecule. Honokiol has several pharmacological effects, leading to its exploration as a potential therapy for neurological diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, anxiety, depression, spinal cord injury, and so on. So, based on the previous experimentation reports, our goal is to discuss the neuroprotective properties of honokiol. Besides, honokiol derivatives have been highlighted recently as possible therapeutic options for NDs. So, this review focuses on honokiol's neurotherapeutic actions and toxicological profile to determine their safety and potential use in neurotherapeutics.

Progress in Fluorescence Biosensing and Food Safety towards Point-of-Detection (PoD) System.

The detection of pathogens in food substances is of crucial concern for public health and for the safety of the natural environment. Nanomaterials, with their high sensitivity and selectivity have an edge over conventional organic dyes in fluorescent-based detection methods. Advances in microfluidic technology in biosensors have taken place to meet the user criteria of sensitive, inexpensive, user-friendly, and quick detection. In this review, we have summarized the use of fluorescence-based nanomaterials and the latest research approaches towards integrated biosensors, including microsystems containing fluorescence-based detection, various model systems with nano materials, DNA probes, and antibodies. Paper-based lateral-flow test strips and microchips as well as the most-used trapping components are also reviewed, and the possibility of their performance in portable devices evaluated. We also present a current market-available portable system which was developed for food screening and highlight the future direction for the development of fluorescence-based systems for on-site detection and stratification of common foodborne pathogens.

Conformational switching of aptamer biointerfacing graphene-gold nanohybrid for ultrasensitive label-free sensing of cardiac Troponin I.

The development of hybrid biofunctionalized nanomaterials has emerged as an attractive substitute for development of advanced biosensing platforms with superior synergistic properties. Herein, we report a label-free ultrasensitive electrochemical aptasensor comprising nanohybrid of graphene oxide (GO) and aptamer conjugated gold nanoparticles (GNP-A) for detection of cardiac biomarker Troponin I (TnI). The GNP-A are homogenously arranged by self-assembly on GO sheet to construct nanohybrid (GO@GNP-A) onto which the biomarker protein is analysed. TnI interactions at the aptamer biointerfaced nanohybrid surface causes electrochemical signal enhancement probed by using a redox active molecule. The consecutive increase in current signal is strongly attributed to conformational switching of aptamer and charge neutralization at the interface induced by TnI binding. The sensitivity of the nanohybrid aptasensor platform was found to be 0.001 pg/mL. The study has been further substantiated in Acute Myocardial Infarction (AMI) clinical samples for usage towards early, sensitive and efficient point-of-care detection of TnI.

Site-directed dual bioprobes inducing single-step nano-sandwich assay for the detection of cardiac troponin I.

Bioreceptor functionalized metallic nano-colloids have been identified as effective nanobioprobes to realize the detection of an analyte based on a common phenomenon of salt-induced aggregation. In marked contrast to this, we describe a nano-sandwich assay integrating the novel match-pair of aptamer and peptide functionalized gold nanoparticles. The site-directed biomolecular interaction of high affinity aptamer and peptide bioreceptors directed towards distinct sites of cardiac biomarker troponin I; this was found to form a nano-sandwich assay in a peculiar manner. The gold nanoconjugates interact with specific and distant regions of troponin I to result in collision of probes upon target identification. In the presence of TnI, both nanobioprobes bind at their respective sites forming a nano-sandwich pair providing a visual color change from red to blue. Thus, the presence of target TnI itself causes instant agglomeration in just a single-step without addition of any external aggregator. The assay imparts 100% specificity and 90% sensitivity in a dynamic concentration range of 0.1-500 ng/mL troponin I with detection limit as low as 0.084 ng/mL. The applicability of the assay has been validated in clinical samples of acute myocardial infarction patients thus establishing a promising point-of-care detection of TnI.

Glycosylation of a key cubilin Asn residue results in reduced binding to albumin.

Kidney disease often manifests with an increase in proteinuria, which can result from both glomerular and/or proximal tubule injury. The proximal tubules are the major site of protein and peptide endocytosis of the glomerular filtrate, and cubilin is the proximal tubule brush border membrane glycoprotein receptor that binds filtered albumin and initiates its processing in proximal tubules. Albumin also undergoes multiple modifications depending upon the physiologic state. We previously documented that carbamylated albumin had reduced cubilin binding, but the effects of cubilin modifications on binding albumin remain unclear. Here, we investigate the cubilin-albumin binding interaction to define the impact of cubilin glycosylation and map the key glycosylation sites while also targeting specific changes in a rat model of proteinuria. We identified a key Asn residue, N1285, that when glycosylated reduced albumin binding. In addition, we found a pH-induced conformation change may contribute to ligand release. To further define the albumin-cubilin binding site, we determined the solution structure of cubilin's albumin-binding domain, CUB7,8, using small-angle X-ray scattering and molecular modeling. We combined this information with mass spectrometry crosslinking experiments of CUB7,8 and albumin that provides a model of the key amino acids required for cubilin-albumin binding. Together, our data supports an important role for glycosylation in regulating the cubilin interaction with albumin, which is altered in proteinuria and provides new insight into the binding interface necessary for the cubilin-albumin interaction.

High-Efficiency Infrared Sensing with Optically Excited Graphene-Transition Metal Dichalcogenide Heterostructures.

Binary van der Waals heterostructures of graphene (Gr) and transition metal dichalcogenide (TMDC) have evolved as a promising candidate for photodetection with very high responsivity due to the separation of photo-excited electron-hole pairs across the interface. The spectral range of optoelectronic response in such hybrids has so far been limited by the optical bandgap of the light absorbing TMDC layer. Here, the bidirectionality of interlayer charge transfer is utilized for detecting sub-band gap photons in Gr-TMDC heterostructures. A Gr/MoSe2 heterostructure sequentially driven by visible and near infra-red (NIR) photons is employed, to demonstrate that NIR induced back transfer of charge allows fast and repeatable detection of the low energy photons (less than the optical band gap of the TMDC layer). This mechanism provides photoresponsivity as high as ≈3000 A W-1 close to the communication wavelength. The experiment provides a new strategy for achieving highly efficient photodetection over a broad range of energies beyond the spectral bandgap with the 2D semiconductor family.

Enhancing Carrier Diffusion Length and Quantum Efficiency through Photoinduced Charge Transfer in Layered Graphene-Semiconducting Quantum Dot Devices.

Hybrid devices consisting of graphene or transition metal dichalcogenides (TMDs) and semiconductor quantum dots (QDs) were widely studied for potential photodetector and photovoltaic applications, while for photodetector applications, high internal quantum efficiency (IQE) is required for photovoltaic applications and enhanced carrier diffusion length is also desirable. Here, we reported the electrical measurements on hybrid field-effect optoelectronic devices consisting of compact QD monolayer at controlled separations from single-layer graphene, and the structure is characterized by high IQE and large enhancement of minority carrier diffusion length. While the IQE ranges from 10.2% to 18.2% depending on QD-graphene separation, ds, the carrier diffusion length, LD, estimated from scanning photocurrent microscopy (SPCM) measurements, could be enhanced by a factor of 5-8 as compared to that of pristine graphene. IQE and LD could be tuned by varying back gate voltage and controlling the extent of charge separation from the proximal QD layer due to photoexcitation. The obtained IQE values were remarkably high, considering that only a single QD layer was used, and the parameters could be further enhanced in such devices significantly by stacking multiple layers of QDs. Our results could have significant implications for utilizing these hybrid devices as photodetectors and active photovoltaic materials with high efficiency.

Synthesis and biological evaluation of heterocyclic 1,2,4-triazole scaffolds as promising pharmacological agents.

BACKGROUND: Triazole is an important heterocyclic moiety that occupies a unique position in heterocyclic chemistry, due to its large number of biological activities. It exists in two isomeric forms i.e. 1,2,4-triazole and 1,2,3-triazole and is used as core molecule for the design and synthesis of many medicinal compounds. 1,2,4-Triazole possess broad spectrum of therapeutically interesting drug candidates such as analgesic, antiseptic, antimicrobial, antioxidant, anti-urease, anti-inflammatory, diuretics, anticancer, anticonvulsant, antidiabetic and antimigraine agents. METHODS: The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR). The synthesized compounds were evaluated for their in vitro antimicrobial activity against Gram-positive (B. subtilis), Gram-negative (P. aeruginosa and E. coli) bacterial and fungal (C. albicans and A. niger) strains by tube dilution method using ciprofloxacin, amoxicillin and fluconazole as standards. In-vitro antioxidant and anti-urease screening was done by DPPH assay and indophenol method, respectively. The in-vitro anticancer evaluation was carried out against MCF-7 and HCT116 cancer cell lines using 5-FU as standards. RESULTS, DISCUSSION AND CONCLUSION: The biological screening results reveal that the compounds T5 (MICBS, EC = 24.7 µM, MICPA, CA = 12.3 µM) and T17 (MICAN = 27.1 µM) exhibited potent antimicrobial activity as comparable to standards ciprofloxacin, amoxicillin (MICCipro = 18.1 µM, MICAmo = 17.1 µM) and fluconazole (MICFlu = 20.4 µM), respectively. The antioxidant evaluation showed that compounds T2 (IC50 = 34.83 µg/ml) and T3 (IC50 = 34.38 µg/ml) showed significant antioxidant activity and comparable to ascorbic acid (IC50 = 35.44 µg/ml). Compounds T3 (IC50 = 54.01 µg/ml) was the most potent urease inhibitor amongst the synthesized compounds and compared to standard thiourea (IC50 = 54.25 µg/ml). The most potent anticancer activity was shown by compounds T2 (IC50 = 3.84 µM) and T7 (IC50 = 3.25 µM) against HCT116 cell lines as compared to standard 5-FU (IC50 = 25.36 µM).

Naturally Inspired Pyrimidines Analogues for Alzheimer's Disease.

Alzheimer's disease (AD) is a multifarious and developing neurodegenerative disorder. The treatment of AD is still a challenge and availability of drug therapy on the basis of symptoms is not up to the mark. In the context of existence, which is getting worse for the human brain, it is necessary to take care of all critical measures. The disease is caused due to multidirectional pathology of the body, which demands the multi-target-directed ligand (MTDL) approach. This gives hope for new drugs for AD, summarized here in with the pyrimidine based natural product inspired molecule as a lead. The review is sufficient in providing a list of chemical ingredients of the plant to cure AD and screen them against various potential targets of AD. The synthesis of a highly functionalized scaffold in one step in a single pot without isolating the intermediate is a challenging task. In few examples, we have highlighted the importance of this kind of reaction, generally known as multi-component reaction. Multi-component is a widely accepted technique by the drug discovery people due to its high atom economy. It reduces multi-step process to a one-step process, therefore the compounds library can be made in minimum time and cost. This review has highlighted the importance of multicomponent reactions by giving the example of active scaffolds of pyrimidine/fused pyrimidines. This would bring importance to the fast as well as smart synthesis of bio-relevant molecules.

Optimal architecture for ultralow noise graphene transistors at room temperature.

The fundamental origin of low-frequency noise in graphene field effect transistors (GFETs) has been widely explored but a generic engineering strategy towards low noise GFETs is lacking. Here, we systematically study and eliminate dominant sources of electrical noise to achieve ultralow noise GFETs. We find that in edge contacted, high-quality hexagonal boron nitride (hBN) encapsulated GFETs, the inclusion of a graphite bottom gate and long (⪆1.2 µm) channel-contact distance significantly reduces noise as compared to global Si/SiO2 gated devices. From the scaling of the remaining noise with channel area and its temperature dependence, we attribute this to the traps in hBN. To further screen the charge traps in hBN, we place few layers of MoS2 between graphene and hBN, and demonstrate that the noise is as low as ∼5.2 × 10-9µm2 Hz-1 (corresponding to minimum Hooge parameter ∼5.2 × 10-6) in GFETs at room temperature, which is an order of magnitude lower than the earlier reported values.

A comprehensive review on biological activities of oxazole derivatives.

The utility of oxazole as intermediates for the synthesis of new chemical entities in medicinal chemistry have been increased in the past few years. Oxazole is an important heterocyclic nucleus having a wide spectrum of biological activities which drew the attention of researchers round the globe to synthesize various oxazole derivatives and screen them for their various biological activities. The present review article aims to review the work reported on therapeutic potentials of oxazole scaffolds which are valuable for medical applications during new millennium.

Benzimidazole scaffolds as promising antiproliferative agents: a review.

Cancer is one of the most serious medical problem and second leading cause of death in the world, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of cellular differentiation and uncontrolled cellular growth. The benzimidazole is a heterocyclic moiety found in extensive number of natural and biological active molecules. Benzimidazole derivatives might be considered as auxiliary isosters of nucleotides having attached heterocyclic cores in their structures, cooperate effortlessly with biopolymers and have potential action for chemotherapeutic applications. Benzimidazole and its derivatives displayed a wide range of biological activity because of its structural similarity with the naturally occurring nucleotides. Benzimidazole has established huge alertness in current time and is extremely significant heterocyclic pharmacophore in recent drug innovation and medicinal chemistry. The present review summarizes the chemistry of various substituted benzimidazole derivatives with their antiproliferative significance towards the various cancer cell lines such as HCT116, MCF7, HeLa, HepG2, A549 and A431.

Optimising graphene visibility in van der Waals heterostructures.

Graphene constitutes one of the key elements in many functional van der Waals heterostructures. However, it has negligible optical visibility due to its monolayer nature. Here we study the visibility of graphene in various van der Waals heterostructures and include the effects of the source spectrum, oblique incidence and the spectral sensitivity of the detector to obtain a realistic model. A visibility experiment is performed at different wavelengths, resulting in a very good agreement with our calculations. This allows us to reliably predict the conditions for better visibility of graphene in van der Waals heterostructures. The framework and the codes provided in this work can be extended to study the visibility of any 2D material within an arbitrary van der Waals heterostructure.

Rapid and sensitive colorimetric detection of pathogens based on silver-urease interactions.

Herein, we demonstrate a facile and economic approach for colorimetric detection of microbial pathogens in drinking water, employing silver-urease interactions. In the presence of harmful pathogens, receptor coated silver nanoparticles (AgNPs) preferentially bind to the bacterial surface and urease catalytically elevates the pH of the solution, which is sensed by a pH responsive chromogenic dye. The assay demarcates bacterial contamination levels up to 102 cells mL-1 in a field-friendly method.

Design, synthesis and biological evaluation of 3-(2-aminooxazol-5-yl)-2H-chromen-2-one derivatives.

BACKGROUND: In view of wide range of biological activities of oxazole, a new series of oxazole analogues was synthesized and its chemical structures were confirmed by spectral data (Proton/Carbon-NMR, IR, MS etc.). The synthesized oxazole derivatives were screened for their antimicrobial and antiproliferative activities. RESULTS AND DISCUSSION: The antimicrobial activity was performed against selected fungal and bacterial strains using tube dilution method. The antiproliferative potential was evaluated against human colorectal carcinoma (HCT116) and oestrogen- positive human breast carcinoma (MCF7) cancer cell lines using Sulforhodamine B assay and, results were compared to standard drugs, 5-fluorouracil and tamoxifen, respectively. CONCLUSION: The performed antimicrobial activity indicated that compounds 3, 5, 6, 8 and 14 showed promising activity against selected microbial species. Antiproliferative screening found compound 14 to be the most potent compound against HCT116 (IC50 = 71.8 µM), whereas Compound 6 was the most potent against MCF7 (IC50 = 74.1 µM). Further, the molecular docking study has been carried to find out the interaction between active oxazole compounds with CDK8 (HCT116) and ER-α (MCF7) proteins indicated that compound 14 and 6 showed good dock score with better potency within the ATP binding pocket and may be used as a lead for rational drug designing of the anticancer molecule.

Design, synthesis and biological potential of heterocyclic benzoxazole scaffolds as promising antimicrobial and anticancer agents.

BACKGROUND: Benzoxazole is the most important class of heterocyclic compound in medicinal chemistry. It has been incorporated in many medicinal compounds making it a versatile heterocyclic compound that possess a wide spectrum of biological activities. RESULTS: The molecular structures of synthesized benzoxazole derivatives were confirmed by physicochemical and spectral means. The synthesized compounds were further evaluated for their in vitro biological potentials i.e. antimicrobial activity against selected microbial species using tube dilution method and antiproliferative activity against human colorectal carcinoma (HCT 116) cancer cell line by Sulforhodamine B assay. CONCLUSION: In vitro antimicrobial results demonstrated that compounds 4, 5, 7 and 16 showed promising antimicrobial potential. The in vitro anticancer activity indicated that compounds 4 and 16 showed promising anticancer activity against human colorectal cancer cell line (HCT 116) when compared to standard drug and these compounds may serve as lead compound for further development of novel antimicrobial and anticancer agents.

Benzoxazole derivatives: design, synthesis and biological evaluation.

BACKGROUND: A new series of benzoxazole analogues was synthesized and checked for their in vitro antibacterial, antifungal and anticancer activities. RESULTS AND DISCUSSION: The synthesized benzoxazole compounds were confirmed by IR, 1H/13C-NMR, mass and screened for their in vitro antimicrobial activity against Gram-positive bacterium: Bacillus subtilis, four Gram-negative bacteria: Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi and two fungal strains: Candida albicans and Aspergillus niger using tube dilution technique and minimum inhibitory concentration (MIC) was noted in µM and compared to ofloxacin and fluconazole. Human colorectal carcinoma (HCT116) cancer cell line was used for the determination of in vitro anticancer activity (IC50 value) by Sulforhodamine B assay using 5-fluorouracil as standard drug. CONCLUSION: The performed study indicated that the compounds 1, 10, 13, 16, 19, 20 and 24 had highest antimicrobial activity with MIC values comparable to ofloxacin and fluconazole and compounds 4, 6, 25 and 26 had best anticancer activity in comparison to 5-fluorouracil.