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Goregaon, India

Himaja M.,Vellore Institute of Technology | Prathap K.J.,Vellore Institute of Technology | Mali S.V.,Piramal Life science
Journal of Heterocyclic Chemistry | Year: 2012

Fused 3,6-disubstituted triazolothiadiazoles were synthesized in good yield from a rapid and convenient oxidative cyclization of N-heteroaryl-substituted hydrazones promoted by chloramine-T trihydrate at ambient temperature. The structure of the synthesized compounds was confirmed by FTIR, 1H NMR, 13C NMR, and mass spectral data. The synthesized compounds were evaluated for their antioxidant and antitubercular activities. All the compounds 5a-i and 6a-i showed good antitubercular activity. However, only compounds 5a-i showed good antioxidant activity. © 2012 HeteroCorporation. Source

Malonia S.K.,National Center for Cell Science | Sinha S.,National Center for Cell Science | Lakshminarasimhan P.,Gothenburg University | Singh K.,Cleveland Clinic Lerner Research Institute | And 4 more authors.
Biochimica et Biophysica Acta - Reviews on Cancer | Year: 2011

Changes in the composition of nuclear matrix associated proteins contribute to alterations in nuclear structure, one of the major phenotypes of malignant cancer cells. The malignancy-induced changes in this structure lead to alterations in chromatin folding, the fidelity of genome replication and gene expression programs. The nuclear matrix forms a scaffold upon which the chromatin is organized into periodic loop domains called matrix attachment regions (MAR) by binding to various MAR binding proteins (MARBPs). Aberrant expression of MARBPs modulates the chromatin organization and disrupt transcriptional network that leads to oncogenesis. Dysregulation of nuclear matrix associated MARBPs has been reported in different types of cancers. Some of these proteins have tumor specific expression and are therefore considered as promising diagnostic or prognostic markers in few cancers. SMAR1 (scaffold/matrix attachment region binding protein 1), is one such nuclear matrix associated protein whose expression is drastically reduced in higher grades of breast cancer. SMAR1 gene is located on human chromosome 16q24.3 locus, the loss of heterozygosity (LOH) of which has been reported in several types of cancers. This review elaborates on the multiple roles of nuclear matrix associated protein SMAR1 in regulating various cellular target genes involved in cell growth, apoptosis and tumorigenesis. © 2010 Elsevier B.V. Source

Himaja M.,Vellore Institute of Technology | Prathap K.J.,Vellore Institute of Technology | Mali S.V.,Piramal Life science | Ramana M.V.,Al Jabal Al Gharbi University
Indian Journal of Heterocyclic Chemistry | Year: 2011

A nevi/ series of 4-(5-methyl-[1,2,4] triazoio [1,5-a] pyrimidin-7-ylamino) -N-(aryl) benzamides (4a-i) were synthesized by coupling 4-(5-methyl-(1,2,4] triazoio [1,5-a] pyrimidin-7-ylamino) benzoic acid 3 with different substituted amines using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) as coupling reagent. The key intermediate 4-(5-methyl-[1,2,4] triazoio [1,5-a] pyrimidin-7-ylamino) benzoic acid 3 was synthesized by the reaction of 7-chloro-5-methyl-[1,2,4] triazoio [1,5-a] pyrimidine 2 with p-aminobenzoic acid in ethanol. The structure of the newly synthesized compounds were confirmed by FT-IR,1H NMR, 13C NMR and Mass spectral analysis and were evaluated for their antimicrobial and insecticidal activities. Some of the synthesized compounds exhibited potent insecticidal activity and significant antibacterial activity with respect to the standard drugs. Source

Chakraborty J.B.,Indian Institute of Chemical Technology | Chakraborty J.B.,Newcastle University | Chakraborty J.B.,Indian Institute of Science | Mahato S.K.,Indian Institute of Chemical Technology | And 22 more authors.
Cancer Science | Year: 2012

Alcoholic extract of Piperbetle (Piper betle L.) leaves was recently found to induce apoptosis of CML cells expressing wild type and mutated Bcr-Abl with imatinib resistance phenotype. Hydroxychavicol (HCH), a constituent of the alcoholic extract of Piper betle leaves, was evaluated for anti-CML activity. Here, we report that HCH and its analogues induce killing of primary cells in CML patients and leukemic cell lines expressing wild type and mutated Bcr-Abl, including the T315I mutation, with minimal toxicity to normal human peripheral blood mononuclear cells. HCH causes early but transient increase of mitochondria-derived reactive oxygen species. Reactive oxygen species-dependent persistent activation of JNK leads to an increase in endothelial nitric oxide synthase-mediated nitric oxide generation. This causes loss of mitochondrial membrane potential, release of cytochrome c from mitochondria, cleavage of caspase 9, 3 and poly-adenosine diphosphate-ribose polymerase leading to apoptosis. One HCH analogue was also effective in vivo in SCID mice against grafts expressing the T315I mutation, although to a lesser extent than grafts expressing wild type Bcr-Abl, without showing significant bodyweight loss. Our data describe the role of JNK-dependent endothelial nitric oxide synthase-mediated nitric oxide for anti-CML activity of HCH and this molecule merits further testing in pre-clinical and clinical settings. © 2011 Japanese Cancer Association. Source

Stanish W.D.,Dalhousie University | McCormack R.,University of British Columbia | Forriol F.,University of San Pablo - CEU | Mohtadi N.,University of Calgary | And 3 more authors.
Journal of Bone and Joint Surgery - Series A | Year: 2013

Background: Microfracture, the standard of care, is recognized to be an incomplete solution for cartilage damage. BST-CarGel, a chitosan-based medical device, is mixed with autologous whole blood and is applied to a microfractured cartilage lesion in which it physically stabilizes the clot and guides and enhances marrow-derived repair. An international, multicenter, randomized controlled trial was conducted to evaluate BST-CarGel treatment compared with microfracture alone in the repair of cartilage lesions in the knee. Methods: Eighty patients between the ages of eighteen and fifty-five years with a single, symptomatic focal lesion on the femoral condyles were randomized to BST-CarGel and microfracture treatment (n = 41) or microfracture treatment alone (n = 39). The primary end points of repair tissue quantity and quality at twelve months were assessed by quantitative three-dimensional magnetic resonance imaging measuring the degree of lesion filling and T2 relaxation time with use of standardized one and twelve-month posttreatment scans. The secondary end point at twelve months was clinical benefit determined with the Western Ontario and McMaster Universities Osteoarthritis Index. The tertiary end point was quality of life determined by the Short Form-36. Safety was assessed through the recording of adverse events. Results: Patient baseline characteristics were similar in the two groups, although baseline lesion areas were slightly larger on quantitative magnetic resonance imaging for the BST-CarGel group compared with the microfracture group. Blinded quantitative magnetic resonance imaging analysis demonstrated that, at twelve months, when compared with microfracture treatment alone, BST-CarGel treatment met both primary end points by achieving statistical superiority for greater lesion filling (p = 0.011) and more hyaline cartilage-like T2 values (p = 0.033). The lesion filling values were 92.8% ± 2.0% for the BSTCarGel treatment group and 85.2% ± 2.1% for the microfracture treatment group, and the mean T2 values were 70.5 ± 4.5ms for the BST-CarGel treatment group and 85.0 ± 4.9 ms for the microfracture treatment group. Western Ontario and McMaster Universities Osteoarthritis Index subscales for pain, stiffness, and function yielded equivalent improvement for both groups at twelve months, which were significant (p < 0.0001) from baseline. Treatment safety profiles were considered comparable. Conclusions: At twelve months, BST-CarGel treatment resulted in greater lesion filling and superior repair tissue quality compared with microfracture treatment alone. Clinical benefit was equivalent between groups at twelve months, and safety was similar. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence. Copyright © 2013 by the journal of bone and joint surgery, incorporated. Source

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