Chandraday Prodhan

A new fluorescence turn-on chemosensor for nanomolar detection of Al3+ constructed from a pyridine–pyrazole system

Herein, a new probe, 5-methyl-1-pyridin-2-yl-1H-pyrazole-3-carboxylic acid (1-pyridin-2-yl-ethylidene)-hydrazide (Hmppc), bearing a pyridine–pyrazole moiety, was synthesized, which offered potential for chemical sensing of Al3+. Investigations of the fluorescence behaviour of Hmppc in DMSO/H2O (2 : 8, v/v) solution under biologically relevant conditions in HEPES buffer (pH = 7.4) displayed a dramatic switch-on response to Al3+ as a result of chelation-induced enhanced fluorescence (CHEF). Detailed experimental studies reveal that Hmppc can detect Al3+ in solution with high sensitivity and selectivity, having a detection limit of 1.2 nM. Furthermore, to demonstrate the analytical potential of Hmppc, we validated our sensing system as a naked eye detector for Al3+. Interestingly, bioimaging studies on HepG2 cells demonstrated that Hmppc responded selectively towards Al3+, allowing real time detection of Al3+ in living cells.

Characterization of a fluorescent hydrogel synthesized using chitosan, polyvinyl alcohol and 9-anthraldehyde for the selective detection and discrimination of trace Fe3+ and Fe2+ in water for live-cell imaging

A three-dimensional fluorescent hydrogel based on chitosan, polyvinyl alcohol and 9-anthraldehyde (ChPA) has been successfully designed and synthesized for the selective detection and discrimination of Fe3+ and Fe2+ in aqueous environment. The unique characteristics of ChPA has been confirmed by the Fourier-transform infrared spectroscopy (FTIR), rheological measurement, scanning electron microscopy (SEM), thermogravimetry and differential thermogravimetry (TG-DTG), ultraviolet-visible spectroscopy (UV-vis), fluorescence studies, transmission electron microscopy (TEM), energy dispersive x-ray spectroscopy (EDX), x-ray diffraction (XRD) and dynamic light scattering (DLS). The emission intensity at 516 nm of the hydrogel has been enhanced remarkably with the addition of Fe3+ due to the inhibition of the photoinduced electron transfer (PET) process. However, it gets strongly quenched in the case of Fe2+ owing to chelation enhanced quenching (CHEQ). The probe (ChPA) causes no significant change in the fluorescence and becomes highly specific and sensitive towards Fe3+ and Fe2+ compared to other interfering heavy and transition metal ions (HTM). The detection limits of the sensor for the Fe3+ and Fe2+ are 0.124 nM and 0.138 nM, respectively. The probe is also promising as a selective sensor for the Fe3+ and Fe2+ in the fluorescence imaging of living cells. Thus, such a probe opens up new opportunities to improve the chitosan based fluorescent chemosensor having biocompatibility, biodegradability, sufficient thermal stability and stability in a wide pH range.

Neo-tanshinlactone D-ring modified novel analogues induce apoptosis in human breast cancer cell via DNA damage

Neo-tanshinlactone (NTL) a natural product is known for its specificity and selectivity towards the breast cancer cells. By NTL D-ring modification approach, 13 new analogues were synthesized (1A-1M). Among them 1J showed the best anticancer activity in MCF-7 (ER+, PR+/-, HER2-), SKBR3 (ER-, PR-, HER2+) and MDA-MB-231 (ER-, PR-, HER2-) cells lines with IC50 value 11.98nM, 23.71nM, and 62.91nM respectively. 1J showed minor grove binding interaction with DNA at AT-rich region and induced DNA double strand breaks (DDSBs). This had triggered several key molecular events involving, activation of ATM, Chk2 and p53, reduction in mitochondrial potential (Δψm) leading to caspase-3 and PARP cleavage mediated apoptosis. These results along with other biochemical studies strongly suggest that novel NTL analogue 1J caused DNA cleavage mediated apoptosis in the breast cancer cells and this may serve as potential lead for future breast cancer treatment.

Identification of over expressed proteins in Oral Submucous Fibrosis by proteomic analysis

Early detection and identification of oral pre‐malignancy or malignancy help in management of the disease and improve survival rates. Oral submucous fibrosis (OSMF) is a major threat to public health worldwide and especially in Southeast Asian countries. Identification of biomarkers is a necessary step toward early diagnosis and treatment. In this study, differentially expressed proteins between oral submucous fibrotic tissue and normal control tissues were recorded by proteomic analysis using two dimensional electrophoresis (2DE) and MALDI TOF mass spectrometry. By proteomic analysis, 15 proteins were found to be upregulated and 10 proteins downregulated in the OSMF tissues than the control tissues; among these identified proteins, Hsp‐70 1B, Calreticulin, and Lumican variant exhibited higher expression in OSMF tissues compared to the control tissues. Immunohistochemical analysis also showed elevated expression of these in OSMF tissues. Further validation was done by real time quantitative RT‐PCR analysis; gene expression of Hsp‐70 1B, Calreticulin, and Lumican variant were significantly increased (6.2‐, 3.3‐, 2.8‐ fold, respectively), whereas Enolase 1 was decreased by 0.5 fold in the OSMF tissues, consistent with proteomic results. The expression of proteins indicates that various cellular signaling pathways must be involved in the processes of fibrosis and suggests that expressed protein molecules play an important role in the pathogenesis of OSMF. These identified proteins may be potentially used in future studies of OSMF enabling to determine diagnostic marker or therapeutic targets of this precancerous condition of oral cavity.

Tripeptide consisting of benzyl protected di-cysteine and phenylalanine forms spherical assembly and induces cytotoxicity in cancer cells via apoptosis

The study of peptide derived self-organized nanoarchitectures is an emerging scientific research area due to its potential application in advanced material science, biointerface engineering, therapeutics etc. In the present study, we report the synthesis and detailed biophysical properties of terminally protected tripeptide ‘N-Boc-L-Phe-S-benzyl-L-Cys-S-benzyl-L-Cys methyl ester’. The solid state FTIR spectrum reveals an intermolecular hydrogen bonded β-sheet like backbone in the solid state. Accordingly, secondary conformation of this tripeptide in the liquid state has been investigated by CD spectroscopy, which demonstrates that the tripeptide preferably exists as an unordered conformation in the liquid phase. Morphology of the self-assembled structure adapted by this tripeptide has been determined by atomic force microscopy (AFM), transmission electron microscopy (TEM) and field emission scanning electron microscopy (FESEM). AFM results revealed that the tripeptide self-assembly behaviour is concentration dependent but independent of the solvent system in which the self-assembled structure was formed. Concentrated methanol solution of the tripeptide produces oligomers 800–1050 nm in size, whereas diluted solutions of tripeptide in ethyl acetate solvent constructs oligomers 350–550 nm in size (diameter). Moreover, this tripeptide retains its self-assembled structure in biological environments i.e. DMEM and FBS also. Furthermore, the tripeptide shows potential cytotoxicity towards cancer cell lines. IC50 values were found to be 6.2 to 7.5 μM against breast (MCF-7, MDA-MB-231) and liver cancer (HepG2) cell lines, estimated by in vitro cell viability assay. Western blot analysis establishes that this tripeptide kills the cancer cells through apoptosis.