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The synthesis of trifluoromethyl phenyl benzamides and their effect on histone acetyltransferase (HAT) activity of p300 is reported. It is found that pentadecyl hydrocarbon chain of (N-(4-chloro-3-trifluoromethyl-phenyl)-2-ethoxy-6-pentadecyl-benzamide) is required to activate the HAT under certain context. more...

Aim: Mammalian DNA Ligases play pivotal role in processes such as DNA replication, recombination, and repair, which qualifies them as potent therapeutic targets to eradicate cancer cells. Recently, we have identified a small molecule inhibitor, SCR7 and its oxidized form SCR7-pyrazine (2-mercapto-6,7-diphenylpteridin-4-ol) (SCR7-P), which can inhibit nonhomologous end-joining (NHEJ) in a Ligase IV-dependent manner. In the present study, we describe a water-soluble version of ligase inhibitor, sodium salt of SCR7-P (Na-SCR7-P) and its anti-tumor effects. Materials and Methods: Water soluble version of SCR7-P was synthesised. To study the inhibitory effect of Na-SCR7-P on ligases, we did in vitro DNA end joining assays using double strand DNA substrates. For this, different concentrations of Na-SCR7-P was used along with purified ligases or cell-free extracts. Further, cytotoxicity induced by Na-SCR7-P was evaluated through trypan blue exclusion assay, JC-1 assay and cell cycle analysis. Anti-tumor activity of Na-SCR7-P was investigated in Swiss albino mice and its off-target effects were studied by conducting kidney and liver test and histological evaluation. Further, the anti-angiogenic effect of the compound was studied using in ovo chorioallantoic membrane assay. Results: Na-SCR7-P inhibited NHEJ in a Ligase IV-dependent manner. However, unlike SCR7 and SCR7-P, it blocked joining catalyzed by all three ligases in vitro, making it an ideal cancer therapeutic agent, as it may target multiple DNA transaction processes within the cancer cells. Na-SCR7-P decreased mitochondrial membrane potential (MMP) leading to cell death in cancer cells. Importantly, the administration of Na-SCR7-P led to a significant reduction in tumor growth from 12th day of treatment, and its impact was significantly higher than previously described SCR7, which targets Ligase IV within cells. Antitumor activity of Na-SCR7-P in mice resulted in enhanced lifespan, with minimal side effects. In addition, the in ovo chorioallantoic membrane assay revealed potent antiangiogenic property of Na-SCR7-P. Conclusion: Our results suggest that Na-SCR7-P can target NHEJ and other DNA repair pathways by disrupting Ligase mediated joining and can potentially be used as a strategy for cancer treatment, owing to its water solubility. more...

An efficient and convenient synthesis of substituted 4 H-chromenes is described using room temperature ionic liquid (RTIL) choline chloride-urea in one pot under solvent free conditions. Three-component Knoevenagel condensation of an aromatic aldehyde, with an active methylene compound, and a cyclohexane dione is reported. This new approach has advantage of excellent yields (82-96%), clean reaction, and short reaction time (15-30 min) at room temperature. [ABSTRACT FROM AUTHOR] more...

Trifluoroethanol is an efficient and recyclable medium in promoting one-pot, three-component condensation reactions of β-ketoesters, aldehydes, and urea (or thiourea) to afford the corresponding dihydropyrimidones in good yields. This protocol does not require the use of an acid or base catalyst. [ABSTRACT FROM PUBLISHER] more...

The kinetics of oxidation of L-amino acids (AAs) glycine( 1a), alanine( 1b), valine( 1c), isoleucine( 1d), leucine( 1e), proline( 1f), and phenylalanine( 1g) by a transition metal ion (Mn3+) was studied in the presence of sulfuric acid medium at 26°C by a spectrophotometrical (λmax = 500 nm) method. In all cases, the kinetics of reactions was of first-order with respect to each [AA] and [Mn3+]. Increased [H+], [Mn2+] (the reduction product of Mn3+), sulfate, and chloride had no effect on the reaction rate. However, the reaction rate increased with increased dielectric constant of the medium. Oxidation rate increased for 1a-gand an apparent correlation was observed between the rate of oxidation and nucleophilicty of AAs except for 1a and 1g. The reaction rate also linearly depended on the hydrophobicity of AAs except for 1f and 1g. The thermodynamic parameters for AA-metal ion complex formation and activation parameters for the rate-limiting steps have been evaluated. Analysis of the oxidation products indicated that the AAs underwent oxidative deamination and decarboxylation to form corresponding aldehydes. Based on these data, plausible mechanisms involved in the oxidation of AAs are proposed. © 2011 Wiley Periodicals, Inc. Int J Chem Kinet 43: 599-607, 2011 [ABSTRACT FROM AUTHOR] more...

α, N-diarylnitrones were synthesized by the reduction of a mixture of nitro-and benzaldehyde derivatives with zinc dust using histidine as a catalyst. [ABSTRACT FROM AUTHOR]