Chemistry

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Shiv Nadar University

Aim: Development of highly sensitive diagnostic nanoprobe for cancer imaging based on surface-enhanced Raman scattering (SERS) platform. Materials & methods: Synthesis of novel squaraine dyes as a Raman signature molecule denoted as lipoic-squaraine-lipoic (LSL), propyl-squaraine-lipoic (PSL) and propyl-squaraine-propyl (PSP). The SERS-nanotag constructed with a Raman signature molecule which is attached on gold nanoparticle and further encapsulated with heterofunctionalized PEG. Antibody conjugation with best SERS-nanotag for target specific recognition. Results: SERS nanotag Au-LSL-PEG showed significant signal intensity and remarkable stability. Anti-EGF receptor and Her2-conjugated Au-LSL-PEG-nanotag were successfully applied for selective recognition of cancer cells like A549, OSCC and MCF7. Conclusion: The newly developed SERS-nanotag Au-LSL-PEG serves as a valuable tool for diagnostic detection of cancer cells, and may find potential applications for cancer screening in real patient samples. © 2015 Future Medicine Ltd.

World University root node

(SoNS) School of Natural Sciences

Nanomedicine

New insight of squaraine-based biocompatible surface-enhanced Raman scattering nanotag for cancer-cell imaging

Long-term real-time visualization of lysosomal dynamics has been challenging at the onset of mitosis due to the lack of fluorescent probes enabling convenient imaging of dividing cells. We developed a long-term real-time photostable mitotic or proliferating marker, CDy6, a BODIPY-derived compound of designation yellow 6, which labels lysosome. In long-term real-time, CDy6 displayed a sharp increase in intensity and change in localization in mitosis, improved photostability, and decreased toxicity compared with other widely used lysosomal and DNA markers, and the ability to label cells in mouse xenograft models. Therefore, CDy6 may open new possibilities to target and trace lysosomal contents during mitosis and to monitor cell proliferation, which can further our knowledge of the basic underlying biological mechanisms in the management of cancer. © 2015 Elsevier Ltd.

Fulltext

Chemistry and Biology

CDy6, a Photostable Probe for Long-Term Real-Time Visualization of Mitosis and Proliferating Cells

Successful application of interfacial engineering for the preparation of cross-linked epoxy microspheres containing thermally polymerizable cardanol-based benzoxazine (Bz-C) monomer in the core is demonstrated. Bz-C is facilely synthesized by Mannich type condensation of cardanol (a by-product of cashew nut industry) and aniline with formaldehyde under solventless conditions. The encapsulation process relies on the preferential reaction of polydimethylsiloxane immiscible epoxy resin and amine-based hardener to form a cross-linked spherical shell at the interface. The microcapsule dimensions and core content could be tailored by modulating the operating parameters, particularly stirring speed and Bz-C: epoxy ratio. Spherical microcapsules with a core content of ∼37\% were obtained when the reaction was carried out at 600 rpm, while maintaining the reaction medium at 70°C with Bz-C: epoxy ratio of 2.3: 1. The simplicity and versatility of the present methodology are the forte of this technique, which widens the scope for large-scale application of benzoxazines in the field of temperature triggered healing. © 2015 Wiley Periodicals, Inc.

Journal of Applied Polymer Science

Interfacial encapsulation of bio-based benzoxazines in epoxy shells for temperature triggered healing

Preclinical Research In this overview, we examine recent developments in network approaches to drug design. A brief overview of networks is followed by a discussion of how chemical similarity networks and their properties address challenges in drug design. Multiple methods used to assess or enhance chemical diversity for early-stage drug discovery are discussed, as well as methods that can be used for drug repositioning and ligand polypharmacology. © 2014 Wiley Periodicals, Inc.

Mathematics

Drug Development Research

Network measures for chemical library design

Here we investigate the solute-medium interaction and solute-centered dynamics in (RCONH2 + LiX) deep eutectics (DEs) via carrying out time-resolved fluorescence measurements and all-atom molecular dynamics simulations at various temperatures. Alkylamides (RCONH2) considered are acetamide (CH3CONH2), propionamide (CH 3CH2CONH2), and butyramide (CH 3CH2CH2CONH2); the electrolytes (LiX) are lithium perchlorate (LiClO4), lithium bromide (LiBr), and lithium nitrate (LiNO3). Differential scanning calorimetric measurements reveal glass transition temperatures (Tg) of these DEs are ∼195 K and show a very weak dependence on alkyl chain-length and electrolyte identity. Time-resolved and steady state fluorescence measurements with these DEs have been carried out at six-to-nine different temperatures that are ∼100-150 K above their individual Tgs. Four different solute probes providing a good spread of fluorescence lifetimes have been employed in steady state measurements, revealing strong excitation wavelength dependence of probe fluorescence emission peak frequencies. Extent of this dependence, which shows sensitivity to anion identity, has been found to increase with increase of amide chain-length and decrease of probe lifetime. Time-resolved measurements reveal strong fractional power dependence of average rates for solute solvation and rotation with fraction power being relatively smaller (stronger viscosity decoupling) for DEs containing longer amide and larger (weaker decoupling) for DEs containing perchlorate anion. Representative all-atom molecular dynamics simulations of (CH3CONH2 + LiX) DEs at different temperatures reveal strongly stretched exponential relaxation of wavevector dependent acetamide self dynamic structure factor with time constants dependent both on ion identity and temperature, providing justification for explaining the fluorescence results in terms of temporal heterogeneity and amide clustering in these multi-component melts. © 2014 AIP Publishing LLC.

Journal of Chemical Physics

Interaction and dynamics of (alkylamide + electrolyte) deep eutectics: Dependence on alkyl chain-length, temperature, and anion identity

Noble metal nanoparticles (NPs) have shown remarkable potential for numerous applications. In this work, a simple, one-pot, green method for the synthesis of gold, silver, palladium, and platinum NPs by using thiol-modified silk fibroin (SF-SH) has been described. The incorporation of thiol groups into silk fibroin (SF) yields small, mono-dispersed metal nanoparticles with good colloidal stability. UV-Vis, transmission electron microscopy (TEM), and X-ray powder diffraction (XRD) analyses show the formation of NPs, and thermo-gravimetric analysis (TGA) data reveal interaction of the NPs with thiol-modified SF. We also show that all the NP-SF conjugates catalyse the reduction of p-nitrophenol to p-aminophenol in the presence of NaBH4 at room temperature. The NP-SF conjugate materials were processed into different material formats like porous scaffolds and films without compromising their individual properties. The Au-SF-SH composite scaffold was used successfully in the heterogeneous catalysis of p-nitrophenol reduction using NaBH4 while the Ag-SF-SH conjugated film showed good antibacterial activity. This journal is © the Partner Organisations 2014.

RSC Advances

Green synthesis of noble metal nanoparticles using cysteine-modified silk fibroin: Catalysis and antibacterial activity

Ferrocene-conjugated copper(ii) complexes [Cu(Fc-aa)(aip)](ClO4) (1-3) and [Cu(Fc-aa)(pyip)](ClO4) (4-6) of l-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (pyip), where Fc-aa is ferrocenylmethyl-l-tyrosine (Fc-Tyr in 1, 4), ferrocenylmethyl-l-tryptophan (Fc-Trp in 2, 5) and ferrocenylmethyl-l-methionine (Fc-Met in 3, 6), were prepared and characterized and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. [Cu(Ph-Met)(aip)](ClO4) (7) and [Cu(Ph-Met)(pyip)](ClO4) (8), were prepared and used as control compounds. The bis-imidazophenanthroline copper(ii) complexes, viz. [Cu(aip)2(NO3)](NO3) (9) and [Cu(pyip) 2(NO3)](NO3) (10), were also prepared and used as controls. Complexes 1-6 having a redox inactive cooper(ii) center showed the Fc+-Fc redox couple at ∼0.5 V vs. SCE in DMF-0.1 mol [Bu n4N](ClO4). The copper(ii)-based d-d band was observed near 600 nm in DMF-Tris-HCl buffer (1:1 v/v). The ferrocenyl complexes showed low dark toxicity, but remarkably high photocytotoxicity in human cervical HeLa and human breast adenocarcinoma MCF-7 cancer cells giving an excellent photo-dynamic effect while their phenyl analogues were inactive. The photo-exposure caused significant morphological changes in the cancer cells when compared to the non-irradiated ones. The photophysical processes were rationalized from the theoretical studies. Fluorescence microscopic images showed 3 and 6 localizing predominantly in the endoplasmic reticulum (ER) of the cancer cells, thus minimizing any undesirable effects involving nuclear DNA. This journal is {\textcopyright} the Partner Organisations 2014.

Dalton Transactions

Ferrocenyl-l-amino acid copper(ii) complexes showing remarkable photo-induced anticancer activity in visible light

Visualization of macrophages in live animals has been of great interest for a better understanding of inflammation. We developed a near infrared (NIR) probe CDnir7 that can selectively detect macrophages and visualize inflammation in vivo using the IVIS spectrum, Fluorescence Molecular Tomography (FMT) and Multi-Spectral Optoacoustic Tomography (MSOT). © The Partner Organisations 2014.

Chemical Communications

A macrophage uptaking near-infrared chemical probe CDnir7 for in vivo imaging of inflammation

Background: Malaria remains the world's most important devastating parasitic disease. Of the five species of Plasmodium known to infect and cause human malaria, Plasmodium falciparum is the most virulent and responsible for majority of the deaths caused by this disease. Mainstream drug therapy targets the asexual blood stage of the malaria parasite, as the disease symptoms are mainly associated with this stage. The prevalence of malaria parasite strains resistance to existing anti-malarial drugs has made the control of malaria even more challenging and hence the development of a new class of drugs is inevitable. Methods: Screening against different drug resistant and sensitive strains of P. falciparum was performed for few bicyclic lactam-based motifs, exhibiting a broad spectrum of activity with low toxicity generated via a focussed library obtained from diversity oriented synthesis (DOS). The synthesis and screening was followed by an in vitro assessment of the possible cytotoxic effect of this class of compounds on malaria parasite. Results: The central scaffold a chiral bicyclic lactam (A) and (A') which were synthesized from (R)-phenylalaninol, levulinic acid and 3-(2-nitrophenyl) levulinic acid respectively. The DOS library was generated from A and from A', by either direct substitution with o-nitrobenzylbromide at the carbon a-to the amide functionality or by conversion to fused pyrroloquinolines. Upon screening this diverse library for their anti-malarial activity, a dinitro/diamine substituted bicyclic lactam was found to demonstrate exceptional activity of >85\% inhibition at 50 μM concentration across different strains of P. falciparum with no toxicity against mammalian cells. Also, loss of mitochondrial membrane potential, mitochondrial functionality and apoptosis was observed in parasite treated with diamine-substituted bicyclic lactams. Conclusions: This study unveils a DOS-mediated exploration of small molecules with novel structural motifs that culminates in identifying a potential lead molecule against malaria. In vitro investigations further reveal their cytocidal effect on malaria parasite growth. It is not the first time that DOS has been used as a strategy to identify therapeutic leads against malaria, but this study establishes the direct implications of DOS in scouting novel motifs with anti-malarial activity. © 2014 Sharma et al.

Malaria Journal

Diversity-oriented synthesis and activity evaluation of substituted bicyclic lactams as anti-malarial against Plasmodium falciparum

Benzoxazine (Bz) monomer was synthesized from renewable cardanol, a by-product from cashew-nut industry, using a solventless approach. The monomer was encapsulated in poly(styrene) (PS) shells by solvent evaporation technique to obtain spherical microcapsules. The microcapsule dimensions and core content could be tailored by optimizing the operating parameters, particularly stirring speed and PS concentration. Successful demonstration of this simple and versatile methodology widens the scope for large-scale application of benzoxazines in the field of self-healing. © 2014 Elsevier Ltd. All rights reserved.