Anuradha Moirangthem

Anion selective chromogenic and fluorogenic chemosensor and its application in breast cancer live cell imaging

A novel Schiff base receptor (L) bearing catechol and phenol groups was synthesized and characterized by various spectral (FTIR, 1H NMR and mass) data. The anion recognition ability of L was investigated by experimental (UV-Vis, fluorescence and 1H NMR) and theoretical (B3LYP/6-31G**) methods. Among the tested anions, the receptor L showed both naked-eye detectable color change from light-yellow to intense brownish-yellow and spectral (hyperchromic shift at 450 nm and ‘turn-on’ fluorescence at 480 nm) changes selectively towards F− and AcO− in DMSO and mixed DMSO–H2O medium because of the formation of a hydrogen bonded anion-receptor complex followed by the deprotonation of L. The receptor L was tested for live breast cancer cell imaging and can be applied to the breast tumour diagnosis.

Simultaneous knockdown of uPA and MMP9 can reduce breast cancer progression by increasing cell-cell adhesion and modulating EMT genes

In cancer progression, proteolytic enzymes like serine proteases and metalloproteinases degrade the basement membrane enabling the tumor cells to invade the adjacent tissues. Thus, invasion and metastasis are augmented by these enzymes. Simultaneous silencing of uPA and MMP9 in breast cancer cells decreased the wound healing, migratory, invasive and adhesive capacity of the cells. After simultaneous down regulation, cells were seen to be arrested in the cell cycle. There was a remarkable increase in the expression of cell to cell adhesion molecule E–cadherin, and decrease in Vimentin and Snail expression. In addition, there was a significant decrease in the expression of the stem cell marker Oct-4. In the breast tumor samples it has been observed that, tumors, expressing higher level of uPA and MMP9, express less amount of E–cadherin. It has also been observed that few tumors also show, Vimentin positive in the ductal epithelial area. Thus, our model can help for checking the aggressive tumor invasion by blocking of uPA and MMP9. Our present observations also give the concept of the presence of aggressive epithelial cells with mesenchymal nature in the tumor micro-environment, altering the expression of EMT genes.

Bioimaging application of a novel anion selective chemosensor derived from vitamin B6 cofactor.

The detection of intracellular fluoride was achieved by a novel Schiff base chemosensor derived from vitamin B6 cofactor (L) using fluorescence imaging technique. The sensor L was synthesized by condensation of pyridoxal phosphate with 2-aminothiophenol. The anion recognition ability of L was explored by UV-Vis and fluorescence methods in DMSO and mixed DMSO-H2O system. The sensor L showed both naked-eye detectable color change from colorless to light green and remarkable fluorescence enhancement at 500 nm in the presence of F(-) and AcO(-). The anion recognition was occurred through the formation of hydrogen bonded complexes between these anions and L, followed by the partial deprotonation of L. The detection limit of L for the analysis of F(-) and AcO(-) was calculated to be 1.88 μM and 9.10 μM, respectively. Finally, the detection of cytoplasmic fluoride was tested using human cancer cell HeLa through fluorescence imaging.

Pyridoxal-thiosemicarbazide: its anion sensing ability and application in living cells imaging

A new anion selective chemosensor L was derived through a direct condensation reaction between pyridoxal and thiosemicarbazide. Sensor L showed selective recognition and sensing ability towards F− and AcO− anions through a naked-eye detectable color change from colorless to light yellow, appearance of a new charge transfer absorption band at 404 nm and significant “turn-on” fluorescence at 506 nm. The detection limit of L as a fluorescent ‘turn-on’ sensor for the analysis of F− and AcO− was estimated to be 0.10 μM. The anion sensing mechanisms of L was supported by 1H NMR and DFT results. Finally, the cytotoxicity effect of L and its ability to image intracellular F− ions in the living HeLa cells was investigated.

Ruthenium(II) complexes of pyrrol-azo ligands: cytotoxicity, interaction with calf thymus DNA and bovine serum albumin

Two ruthenium(II) complexes of newly designed pyrrol-azo ligands(L) and bipyridine(bpy) formulated as [Ru(L)(bpy)2]ClO4, where HL1 = (4-chloro-phenyl)-(1H-pyrrol-2-yl)-diazene (1) complex 1 and HL2 = (4-nitro-phenyl)-(1H-pyrrol-2-yl)-diazene for 2, were isolated in pure form. The complexes were characterized by physicochemical and spectroscopic methods. The electrochemical behavior of the complexes showed the Ru(III)/Ru(II) couple at different potentials with quasi-reversible voltammograms. The study of cytotoxicity effects of 1 and 2 on human breast cancer cells (MCF 7, MDA-MB 231) and cervical cancer cell (HeLa) taking Cisplatin as a positive reference showed that 1 exhibited higher cytotoxicity against cancer cell lines than 2, but less activity than Cisplatin. The interaction of 1 with calf thymus DNA (CT-DNA) using absorption, emission spectral studies, viscosity-measurement, and electrochemical techniques has been used to determine the binding constant K b and the linear Stern–Volmer quenching constant K SV. The results indicate that 1 strongly interacts with CT-DNA in groove binding mode. The interaction of bovine serum albumin (BSA) with 1 was also investigated with the help of spectroscopic tools. Absorption spectroscopy proved the formation of a BSA-[Ru(L1)(bpy)2]ClO4 complex.

Expression of matrix metalloproteinase-2 and 9 in cervical intraepithelial neoplasia and cervical carcinoma among different age groups of premenopausal and postmenopausal women

AbstractPurposeThe objective was to study the gelatinolytic activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in preinvasive and invasive carcinoma of the uterine cervix. The expressions were analysed against different age groups, as to demonstrate whether the expression of MMP-2 and MMP-9 is an early or a late event during the progression of cervical cancer. Additionally, the diagnostic accuracy of MMP-2 and MMP-9 was evaluated with ROC curve.MethodsA total number of 180 samples of cervical tissue were studied for MMP-2 and MMP-9 gelatinolytic activity. The cases were selected as to include 63 normal cases, 94 CIN cases and 23 cervical carcinoma cases. Among 94 CIN cases, 40 were CIN1, 26 were CIN2 and 28 were CIN3, as reported by histopathology. The gelatinolytic activities of MMP-2 and MMP-9 were evaluated by gelatin zymography in premenopausal and postmenopausal groups.ResultsMMP-2 expressions (latent and active) were very low in control samples, followed by increase in CIN1, decrease in CIN2 and further increase in advance stages. MMP-9 had also shown the same expression pattern that of MMP-2. While comparing the expression of MMP-2 and MMP-9 in different age groups, we found initial CIN stages were prevalent in early age that expressed considerable amount of MMP-2 and MMP-9, and advance stages of carcinoma cervix were prevalent at an elderly age.ConclusionBoth MMP-2 and MMP-9 have role in cancer progression and remodelling of the ectocervix. Although expression level varies intricately, a distinctive ROC curve demonstrated MMP-2 active form and MMP-9 form could be used in diagnostic purpose in detection of cervical lesion and cancer.

Advances of Non-Surgical Therapy for Different Molecular Subtypes ofBreast Cancer

Breast cancer is one of the most commonly diagnosed and leading cause of death in women. It has been estimated that 25% of the cancer cases are due to breast cancer alone and accounts for 15% cancer related deaths in women.

Efficient and Convenient Methods for Synthesis of Some Phthalazine Derivatives and Their Evaluation of Cytotoxicity

Abstract A systematic study of the reaction of 1,4-dihydrazinophthalazine (DHPH) with 1,3-dicarbonyls [viz., acetylacetone (acac), dibenzoylmethane (bzbz), and 1-benzoylacetone (bzac)] varying the reaction conditions was carried out to obtain the phthalazine derivatives (1–4). One-pot reaction of DHPH with acac led to the formation of two compounds 1 and 2, with various factors such as the presence of the acid or base, amount of the acac, time of reflux, and the temperature. The reaction conditions of DHPH with bzbz or bzac are sort of different to isolate the products 3 and 4, respectively. The derivatives (1–4) have been characterized by elemental analyses, 1H NMR, and electrospray ionization–mass spectrometry (ESIMS) and the cytotoxic activity of the compounds 1–4 was evaluated on HeLa cell line. [Supplementary materials are available for this article. Go to the publishers online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.] GRAPHICAL ABSTRACT