Liao C.-H.Chang Y.-L.JIH-HWA GUHKuo S.-C.Huang L.-J.Teng C.-M.2021-06-022021-06-022002223573https://www.scopus.com/inward/record.uri?eid=2-s2.0-0035990602&doi=10.1211%2f002235702760089090&partnerID=40&md5=53623bb5a085b96bab4e1ef62f59a325https://scholars.lib.ntu.edu.tw/handle/123456789/564889Because the metabolites of arachidonic acid participate in many physiopathological responses, including inflammation and platelet aggregation, cyclooxygenase inhibitors are important in the treatment of associated diseases. A biologically active compound, 5-ethyl-4-methoxy-2-phenyl-quinoline (KTC-5), selectively and concentration dependently inhibited aggregation of platelets from man and ATP release caused by arachidonic acid (200 μM) and collagen (10 μg mL-1) without affecting the aggregation caused by thrombin (0.1 U mL-1) and U46619 (2 μM). The IC50 value (drug concentration inhibiting maximum response by 50%) of KTC-5 for aggregation induced by arachidonic acid and collagen was 0.11±0.04 μM and 0.20±0.03 μM, respectively. This inhibitory effect of KTC-5 was reversible and time dependent. KTC-5 specifically inhibited intracellular calcium mobilization initiated by arachidonic acid or collagen without affecting that caused by thrombin or U46619 in human platelets. Furthermore, KTC-5 inhibited thromboxane B2 and prostaglandin D2 formation provoked by arachidonic acid. The IC50 value of KTC-5 for arachidonic-acid-induced thromboxane B2 formation was 0.07±0.02 μM. Based on these observation, the data indicated that KTC-5 potently inhibited human platelet aggregation and ATP release mainly via the inhibition of the cyclooxygenase-1 activity. Moreover, KTC-5 inhibited lipopolysaccharide-induced prostaglandin E2 formation in RAW264.7 cells in the presence of external arachidonic acid with an IC50 value of 0.17±0.06 μM. Immunoblot analysis showed that KTC-5 did not affect the cyclooxygenase-2 expression in the presence of lipopolysaccharide on RAW264.7 cells. This result indicated that KTC-5 affects the activity of cyclooxygenase-2. According to these data, we concluded that KTC-5 is a cyclooxygenase inhibitor for both subtypes.[SDGs]SDG315 hydroxy 11alpha,9alpha epoxymethanoprosta 5,13 dienoic acid; 5 ethyl 4 methoxy 2 phenylquinoline; adenosine triphosphate; arachidonic acid; calcium; collagen; cyclooxygenase 1; cyclooxygenase 2; imidazole; indometacin; ktc 5; lipopolysaccharide; prostaglandin D2; prostaglandin E2; prostaglandin synthase inhibitor; thrombin; thromboxane B2; unclassified drug; 5 ethyl 4 methoxy 2 phenylquinoline; 5-ethyl-4-methoxy-2-phenylquinoline; adenosine triphosphate; arachidonic acid; collagen; prostaglandin synthase inhibitor; quinoline derivative; animal cell; article; calcium cell level; calcium mobilization; cell line; concentration (parameters); concentration response; controlled study; dose time effect relation; drug effect; drug mechanism; drug potency; drug selectivity; drug specificity; enzyme activity; enzyme inhibition; human; human cell; IC 50; immunoblotting; inhibition kinetics; metabolic inhibition; mouse; nonhuman; peritoneum macrophage; protein determination; protein expression; protein synthesis inhibition; thrombocyte; thrombocyte aggregation inhibition; culture technique; enzymology; kinetics; secretion; thrombocyte; thrombocyte aggregation; Adenosine Triphosphate; Arachidonic Acid; Blood Platelets; Cell Culture Techniques; Collagen; Cyclooxygenase Inhibitors; Humans; Kinetics; Platelet Aggregation; Quinolinesjournal article10.1211/002235702760089090121627162-s2.0-0035990602