Objective: Polypharmacology, interaction of one drug with multiple targets, emerged as an effective approach in drug discovery and development. Bioinformatics and cheminformatics methods are essential tools for determination of polypharmacological profiles of newly synthesized or known compounds and drugs. Previously, three novel triazolothiadiazine derivatives; 1h, 3c and 3h, have been shown to induce apoptosis and cause cell cycle arrest on liver cancer cells. The aim of this study is to find possible action mechanisms and potential targets for these three triazolothiadiazine derivatives, and to investigate their potential as new therapeutic agents by using computational methods. Materials and Methods: PASS software was used to identify biological activities and Swiss Target Prediction and BindingDB databases to predict potential targets for 1h, 3c and 3h. PDE4A, ALR and DUSP1 proteins were selected for molecular docking analysis following the protein modeling of the three proteins. Results: Activity prediction results show that 1h, 3c and 3h might have phosphatase and signal transduction pathway inhibitor, hepatocyte growth factor antagonist, anti-inflammatory and antifungal activities. These derivatives are predicted as inhibitors of several phosphodiesterases by activity and target prediction tools. Conclusion: Based on prediction and molecular docking results, it is proposed that these compounds may have therapeutic properties through new predicted targets.
Background: This study aimed to evaluate the efficacy and safety of oral hydrolyzed collagen peptide (HCP) in healthy females by assessing the skin parameters via biophysical and skin imaging techniques. Methods: 112 females were randomly assigned to receive either HCP (n = 57; 10 g CollaSel Pro®) or placebo (n = 55; 10 g maltodextrin) daily for eight weeks. The contribution of HCP to skin elasticity, hydration, and roughness was investigated against a placebo, while the facial soft tissue sagging (RMS) and safety data were also recorded. Results: HCP was associated with significant improvements in skin elasticity (p = 0.009), skin hydration (p ranged from 0.003 to <0.001), and skin roughness (p ranged from 0.002 to <0.001). In the HCP vs. the placebo group, week eight values for skin elasticity (43.0 (7.4) vs. 40.3 (3.3) mPa, p = 0.017), skin hydration (65.8 (18.9) vs. 53.1 (14.9) g/m3, p < 0.001) and skin roughness (40.2 (20.4) vs. 24.9 (20.9) g/m3, p < 0.001) were significantly higher. In the HCP group, week 8 RMS values were significantly lower than baseline values (1.02 (0.21) vs. 1.10 (0.21) mm, p = 0.012). Conclusions: CollaSel Pro® HCP can be considered a well-tolerated, safe product that effectively improves dermal health and the appearance of sagging and ameliorates the signs of the aging process.
11 May 2023 in Turkish Journal of Pharmaceutical Sciences
Objectives: Dexketoprofen is a non-steroidal analgesic/anti-inflammatory drug and its trometamol salt is extensively preferred in mild or moderate pain due to its rapid onset of relief. A new formulation of 36.9 mg of dexketoprofen trometamol (equivalent to 25 mg dexketoprofen) tablet has been developed and its bioequivalence to the reference product was proven. Materials and Methods: An open-label, single-dose, randomized, two-period, and cross-over bioequivalence study was conducted with healthy males under fasting conditions for two different tablet formulations of 25 mg dexketoprofen. To prove the bioequivalence of the test product with the reference product, a comparison study has been performed in compliance with regulations in force under Good Clinical Practice principles. A single-center clinical study was run and blood samples of the participants were withdrawn at specified time points, before and after dosing, to measure the plasma concentrations of dexketoprofen trometamol. A validated analytical method has been developed using an liquid chromatography with tandem mass spectrometry. Instrument to assess the plasma concentrations of the test and reference products. Results: Forty-seven volunteers completed clinical phase of the study. For the test and reference products, the mean +/- standard deviations (SD) of Cmax were found 2543.82 +/- 655.42 ng/mL and 2539.11 +/- 662.57 ng/mL, and the mean +/- SD of area under the curve (AUC) from time 0 to the last measurable concentration (AUC(0-tlast)) were found 3483.49 +/- 574.42 h.ng/mL and 3560.75 +/- 661.83 h.ng/mL, respectively. The primary target variables data demonstrate the bioequivalence of test and reference products with regard to 90% confidence interval for Cmax of 92.45-108.53% and for AUC(0-tlast)of 95.57-100.87%. The geometric mean ratios were found as 100.16% and 98.18% for Cmax and AUC(0-tlast), respectively. There were no serious adverse events or adverse reactions reported throughout the study. Conclusion: After statistical evaluation of the analytical results, the test and reference products were considered bioequivalent. Both products were well tolerated and considered as safe.
26 September 2022 in Fabad Journal of Pharmaceutical Sciences
A new oral formulation of cefdinir, Cefdinir 600 mg Tablets has been developed and in this study, its relative bioavailability has been compared with another oral solid dosage form, Cefdinir 300 mg Capsules, which is already on the market. An open-label, randomized, two-period, cross-over relative bioavailability study has been conducted with healthy males under fasting conditions in compliance with Good Clinical Practice (GCP) principles. A single dose of the novel tablet formulation of 600 mg cefdinir has been compared to two doses of Cefdinir 300 mg Capsules (two capsules at once) in terms of their pharmacokinetic properties. The comparison study was performed as a single-center clinical study, and blood samples of the participants were withdrawn at specified time points, before and after dosing. The plasma concentrations and pharmacokinetic properties of two cefdinir formulations were assessed from the collected samples by using a validated LC-MS/MS analytical method. The relative bioavailability of the new formulation has been shown and both products were introduced as safe.