Design, synthesis and antiplatelet activity evaluation of novel quinoxaline antagonists of protease activated receptor 4 (PAR4) / 药学学报

Twenty-five compounds of novel quinoxaline-based scaffold with antiplatelet activity were designed and synthesized on the basis of previous quinoxaline analogues, and the structures were confirmed by 1H NMR, 13C NMR, and MS. The antiplatelet activity was evaluated, structure-activity relationship (SAR) study was summarized and the selectivity of PAR4 was confirmed by calcium mobilization assays. It was indicated that compound 14a, 14g, 13i, 13p showed moderate activity against PAR4, especially, the activity of compound 14g (IC50 = 0.26 μmol·L-1) was 6.7 times than the lead compound A (IC50 = 1.73 μmol·L-1). Therefore, 2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline and [1,3]dioxolo[4,5-g]quinoxaline derivatives are promising compounds for the discovery of novel antiplatelet agents. It is worthy of further research to develop highly effective and selective PAR4 antagonists.

Recent Developments And Multiple Biological Activities Available With 1, 8-Naphthyridine Derivatives: A Review

Within the wide range of nitrogen-containing heterocyclic compounds, the derivatives of 1,8-naphthyridine (NPTR) have gained a rising interest due to their reported versatile biological activities. The derivatives of NPTR scaffold are found to invite special interest from researchers nowadays on the significance of their manifestations of multiple attractive pharmacological activities which establish them as an effective and versatile tool in pharmaceutical chemistry and drug discovery. The diverse biological activities mainly include anti-inflammatory, antimicrobial, antiviral, anticancer, antihypertensive and analgesic activities. Novel NPTR scaffold has emerged its potency to treat neurological diseases like depression and Alzheimer's disease. Further these agents possess different inhibitory activities, such as anti-HIV, anti-osteoporotic, αvβ3 antagonism, antimalarial, platelet aggregation, anti-oxidant, anti-allergic, gastric antisecretory, anticonvulsant, epidermal growth factor receptor (EGFR) inhibition, protein kinase inhibition, ionotropic properties, β3 antagonism, phosphodiesterase 4 (PDE 4) inhibitions, adenosine receptor agonistic activity, adrenoceptors antagonism and DNA stabilizing activity, etc. In this review, we highlight the updates of different 1,8-naphthyridine derivatives and explain the key data available in the context of various biological activities of NPTR derivatives available from the literature. This may direct opportunity in researches in the synthesis of novel medicinal agents and the development of new heterocycles for modification of existing biological actions as well as evaluation of other possible pharmacological activities.

Biological Activities of the Hydro-alcoholic and Aqueous Extracts of Achillea falcata L. (Asteraceae) Grown in Jordan.

Aim: This study aimed to screen the aqueous and hydro-alcoholic extracts of Achillea falcata L. (Asteraceae) grown in Jordan for their antioxidant, antibacterial, antiplatelet and anti-proliferative efficacy. Study Design: HPLC-MS evaluation of the aqueous and hydro-alcoholic extracts and in vitro investigations. Place and Duration of Study: Faculties of Pharmacy and Science, The University of Jordan and Centre of Misanalysis, National Institute for Biological Sciences, between August 2012 and June 2013. Methodology: Total phenols and flavonoids were determined colorimetrically. The radical scavenging activities were evaluated using 2,2′-azino-bis-3-ethylbenzthiazoline-6- sulphonic acid (ABTS) radical scavenging activity assay. Antimicrobial activities were determined by the disc-diffusion method, and the minimum inhibition concentration and the minimum bactericidal concentration tests. In vitro antiplatelet activity was tested on human whole blood using an electrical impedance method. Anti-proliferative activity was investigated using the MTT assay. High performance liquid chromatography-mass spectrometry (HPLC-MS) evaluation was performed. Results: Hydro-alcoholic extract had a bactericidal activity against Streptococcus pneumoniae, Bacillus cereus and Klebsiella pneumoniae rather than inhibitory effect. No significant activity was observed against gram negative bacteria and Candida albicans. In vitro antiplatelet activity was tested on human whole blood using an electrical impedance method. At concentrations (50, 100, and 200 μg/ml), hydro-alcoholic extract did not show effect on platelet aggregation. Extracts did not possess cytotoxic activity against the MCF- 7 cells at concentrations up to 200 μg/ml. HPLC-MS analysis resulted in the identification of 8 phenolic compounds in the hydro-alcoholic extract and 6 compounds in the aqueous extract; quercetin 3-β-D-glucoside was the main component for both extracts. Conclusion: The present investigation supported the traditional use A. falcata in the Jordanian folk medicine as a depurative agent and as an antimicrobial active representative of the genus Achillea.