Background: At present, ‘pharmaco-epigenomics’ constitutes the hope in cancer treatment owing to epigenetic deregulation- a reversible process and playing a role in malignancy. Objective: Chemotherapy has many limitations like host-tissue toxicity, drug resistance. Hence, it is imperative to unearth targets to better treat cancer. Here, we intend to repurpose a set of our previously synthesized difluorinated Propanediones (PR) as Histone lysine Methyltransferase inhibitors (HMTi). Methods: The cell lines of leukemic origin viz. histiocytic lymphoma (U937) and acute T-cell leukemia (JURKAT) were treated with PR-1 to 7 after docking studies with active pocket of HMT. The cell cycle analysis, in vitro methylation and cell proliferation assays were carried out to delineate their physiological role. Results: A small molecule PR-4, at 1 and 10µM, has shown to alter the methylation of histone H3 and H4 in both cell lines. Also, treatment shows an increase in G2/M population and a subsequent decrease in the G0/G1 population in U937. In JURKAT, an increase in both G2/M and S phase population was observed. The sub-G1 population showed a steady rise with increase in dose and prolonged time intervals in U937 and JURKAT cell lines. In SRB assay, the PR showed a cell growth of 42.6 and 53.4% comparable to adriamycin; 44.5 and 53.2% in U937 and JURKAT, respectively. The study suggests that PR-4 could emerge as a potential HMT inhibitor. Conclusion: The molecule PR-4 could be a lead in developing more histone lysine methyltransferases inhibitors with potential to be pro-apoptotic agents.

2018-04-01·European Journal of Sport Science2区 · 医学

Active recovery intervals restore initial performance after repeated sprints in swimming^*

2区 · 医学

Article

作者: Toubekis, Argyris G. ; Volaklis, Konstantinos ; Kostoulas, Ioannis D. ; Paxinos, Thrasivoulos ; Tokmakidis, Savvas P.

ABSTRACTThe purpose of this study was to examine the effects of active recovery (AR) and passive recovery (PR) using short (2‐min) and long (4‐min) intervals on swimming performance. Twelve male competitive swimmers completed a progressively increasing speed test of 7 × 200‐m swimming repetitions to locate the speed before the onset of curvilinear increase in blood lactate concentration (LT1). Subsequently, performance time of 6 × 50‐m sprints was recorded during four different conditions: (i) 2‐min PR (PR‐2), (ii) 4‐min PR (PR‐4), (iii) 2‐min AR (AR‐2) and (iv) 4‐min AR (AR‐4) intervals. Blood lactate concentration was measured before the first and after the last 50‐m repetition. AR was applied at an intensity corresponding to LT1. Performance as indicated by the time needed to complete 6 × 50‐m sprints was impaired after AR‐4 compared to PR‐4 (AR‐4: 28.65 ± 1.04, PR‐4: 28.17 ± 0.72 s; mean% difference: MD% ±s; ±90% confidence limits: 90%CL, 1.71 ± 3.01%; ±1.43%, p = .01) but was not different between AR‐2 compared to PR‐2 conditions (AR‐2: 28.68 ± 0.85, PR‐2: 28.69 ± 0.82 s; MD%: 0.03 ± 1.61%; 90%CL ± 0.77%, p = .99). Performance in sprint‐6 was improved after AR compared to PR independent of interval duration (AR: 28.55 ± 0.81, PR: 29.01 ± 1.03 s; MD%: 1.52 ± 2.61%; 90%CL ± 1.2%; p = .03). Blood lactate concentration was lower after AR‐4 compared to PR‐4 but did not differ between AR‐2 and PR‐2 conditions. In conclusion, AR impaired performance after a 4‐min but not after a 2‐min interval. A better performance during sprint‐6 after AR could be attributed to a faster metabolic recovery or anticipatory regulatory mechanisms towards the end of the series especially when adequate 4‐min active recovery interval is applied.

Journal of Chromatographic Science4区 · 化学

Impact of Ternary Solvent System in Stability-Indicating Assay Method of Bambuterol: Design of Experiments Approach

4区 · 化学

Article

作者: Abiramasundari, A ; Sharma, Jayesh ; Pandya, Dhaivat ; Joshi, Rahul ; Vasu, Kamala K ; Sudarsanam, V ; Joshi, Amita

High-performance liquid chromatography method for anti-asthmatic β2-agonist drug bambuterol, its process-related impurities and its major degradation products was developed and validated using quality by design concept. A 3(3) full factorial design was employed to study the effect of three independent factors, namely, ratio of organic modifiers in mobile phase, pH of the buffer and flow rate of the mobile phase. The responses considered were retention time of the last peak and resolution of poorly separated peaks (drug and PR-4 and drug and DP-3). The optimum conditions for separation were determined with the aid of design of experiments. The optimized ternary solvent composition was a mixture of 10 mM ammonium acetate buffer (pH 6.0), methanol and acetonitrile in the ratio of 90:5: 5 (v/v/v) in solvent reservoir A and 10:45:45 (v/v/v) in solvent reservoir B. The separation of the analytes was achieved by using a gradient method. The predictability criteria of the optimized method demonstrated good correlation between observed and predicted response. The method was validated for specificity, linearity, accuracy, precision and robustness in compliance with the International Conference on Harmonization guidelines Q2R1.

100 项与 PR-004 相关的药物交易

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