scholarly journals Design, Synthesis, Docking Study and Antiplatelet Evaluation of New Thiosemicarbazide Derivatives Derived from Captopril

2019 ◽  
Vol 35 (2) ◽  
pp. 829-838
Author(s):  
Hiba Najeh Al-Saad ◽  
Ammar Abdul Razzak Mahmood ◽  
Redha I. Al-Bayati
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Binding Energy ◽  
Enzyme Inhibitor ◽  
Adenosine Diphosphate ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Percent Inhibition ◽  
Thiosemicarbazide Derivatives ◽  
Cox 1

A series of thiosemicarbazide derivatives of captopril, a well-known angiotensin-converting enzyme inhibitor ACEI, have been synthesized by reaction of hydrazide of captopril with different phenylisothiocyanate substituents. The synthesized compounds were characterized using FTIR, 1HNMR and CHNS analysis. The final derivatives were tested for antiplatelet activity using multiplate analyzer and adenosine diphosphate (ADP), arachidonic acid (AA), and collagen, as platelet aggregation inducers. Among tested compounds, derivative 7 and 10 were the most potent inhibitors of platelet aggregation induced by arachidonic acid, with percent inhibition (97.14±0 and 95.71±2.02) and IC50 (2.7 and 1.21μgml), respectively. Molecular docking study was performed using purino receptor P2Y12, COX-1, and glycoprotein llbllla as the target protein, compound 7 has a potential to become as a lead molecule for COX-1 inhibitor with binding energy (-10.67) Kcal/mol. Also, compound 6 was found as the best inhibitor for the glycoprotein IIa/IIIb with percent inhibition (83.9±2.8), and binding energy (-10.05) Kcal/mol.

scholarly journals Inhibitory Mechanisms of Lusianthridin on Human Platelet Aggregation

2021 ◽  
Vol 22 (13) ◽  
pp. 6846
Author(s):  
Hla Nu Swe ◽  
Boonchoo Sritularak ◽  
Ponlapat Rojnuckarin ◽  
Rataya Luechapudiporn
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Docking Studies ◽  
Secondary Wave ◽  
Inhibitory Effects ◽  
Antiplatelet Aggregation ◽  
Cyclooxygenase 1 ◽  
Cox 2 ◽  
Cox 1

Lusianthridin is a phenanthrene derivative isolated from Dendrobium venustum. Some phenanthrene compounds have antiplatelet aggregation activities via undefined pathways. This study aims to determine the inhibitory effects and potential mechanisms of lusianthridin on platelet aggregation. The results indicated that lusianthridin inhibited arachidonic acid, collagen, and adenosine diphosphate (ADP)-stimulated platelet aggregation (IC50 of 0.02 ± 0.001 mM, 0.14 ± 0.018 mM, and 0.22 ± 0.046 mM, respectively). Lusianthridin also increased the delaying time of arachidonic acid-stimulated and the lag time of collagen-stimulated and showed a more selective effect on the secondary wave of ADP-stimulated aggregations. Molecular docking studies revealed that lusianthridin bound to the entrance site of the cyclooxygenase-1 (COX-1) enzyme and probably the active region of the cyclooxygenase-2 (COX-2) enzyme. In addition, lusianthridin showed inhibitory effects on both COX-1 and COX-2 enzymatic activities (IC50 value of 10.81 ± 1.12 µM and 0.17 ± 1.62 µM, respectively). Furthermore, lusianthridin significantly inhibited ADP-induced suppression of cAMP formation in platelets at 0.4 mM concentration (p < 0.05). These findings suggested that possible mechanisms of lusianthridin on the antiplatelet effects might act via arachidonic acid-thromboxane and adenylate cyclase pathways.

Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibition activities and molecular docking study of pyrazoline derivatives

2016 ◽  
Vol 24 (9) ◽  
pp. 2032-2042 ◽  
Author(s):  
Maged A. Abdel-Sayed ◽  
Said M. Bayomi ◽  
Magda A. El-Sherbeny ◽  
Naglaa I. Abdel-Aziz ◽  
Kamal Eldin H. ElTahir ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Molecular Docking Study ◽  
Anti Inflammatory ◽  
Cox 1

COX-1/COX-2 inhibition activities and molecular docking study of newly designed and synthesized pyrrolo[3,4-c]pyrrole Mannich bases

2019 ◽  
Vol 27 (17) ◽  
pp. 3918-3928 ◽  
Author(s):  
Aleksandra Redzicka ◽  
Łukasz Szczukowski ◽  
Andrzej Kochel ◽  
Benita Wiatrak ◽  
Katarzyna Gębczak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Study ◽  
Mannich Bases ◽  
Molecular Docking Study ◽  
Cox 2 ◽  
Cox 1

scholarly journals Effect of alteplase on platelet function and receptor expression

2019 ◽  
Vol 47 (4) ◽  
pp. 1731-1739 ◽  
Author(s):  
Jun Lu ◽  
Peng Hu ◽  
Guangyu Wei ◽  
Qi Luo ◽  
Jianlin Qiao ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Platelet Function ◽  
Adenosine Diphosphate ◽  
Receptor Expression ◽  
Light Transmittance ◽  
Dependent Manner ◽  
Clot Retraction ◽  
Platelet Receptors

Objective To investigate the role of alteplase, a widely-used thrombolytic drug, in platelet function. Methods Human platelets were incubated with different concentrations of alteplase followed by analysis of platelet aggregation in response to adenosine diphosphate (ADP), collagen, ristocetin, arachidonic acid or epinephrine using light transmittance aggregometry. Platelet activation and surface levels of platelet receptors GPIbα, GPVI and αIIbβ3 were analysed using flow cytometry. The effect of alteplase on clot retraction was also examined. Results This study demonstrated that alteplase significantly inhibited platelet aggregation in response to ADP, collagen and epinephrine in a dose-dependent manner, but it did not affect ristocetin- or arachidonic acid-induced platelet aggregation. Alteplase did not affect platelet activation as demonstrated by no differences in P-selectin levels and PAC-1 binding being observed in collagen-stimulated platelets after alteplase treatment compared with vehicle. There were no changes in the surface levels of the platelet receptors GPIbα, GPVI and αIIbβ3 in alteplase-treated platelets. Alteplase treatment reduced thrombin-mediated clot retraction. Conclusions Alteplase inhibits platelet aggregation and clot retraction without affecting platelet activation and surface receptor levels.

A Study of Intravascular Platelet Aggregation in the Rat

1979 ◽  
Author(s):  
G. G. Duncan ◽  
G. M. Smith
Keyword(s):  
Arachidonic Acid ◽  
Platelet Count ◽  
Platelet Aggregation ◽  
Thromboxane A2 ◽  
Adenosine Diphosphate ◽  
Residual Response ◽  
Induced Aggregation ◽  
Anaesthetized Rat

Intravascular platelet aggregation can be studied by measuring the fall in the circulating platelet count induced by aggregating agents in anaesthetized animals. The Technicon Auto-counter was modified and connected via a double cannula to an anaesthetized rat to give a continuous count of the number of circulating platelets (1). Adenosine diphosphate (ADP), Collagen, Arachidonic acid (AA) and 5-Hydroxytryptamine (5-HT) were given at 15 minute intervals over a period of 2-3 hours. Aspirin (10 mg/Kg IV ) and Indomethacin (1-8 mg/Kg IV) partially inhibited collagen-induced aggregation and Indomethacin (2 mg/Kg IV) completely inhibited AA-induced aggregation. Adenosine (0.25 mg/min) inhibited the ADP-induced aggregation but did not inhibit aggregation produced by collagen or the residual response to collagen that remains after the addition of indomethacin.Reproducible responses to ADP and collagen were obtained but responses to AA and 5-HT were not reliable. Collagen-induced aggregation is thought to be mediated by the liberation of ADP, 5-HT and the formation of prostaglandin (PG ) endoperoxides and thromboxane A2. This study has shown that collagen-induced aggregation is reduced by inhibition of PG synthesis but the involvement of ADP or 5-HT could not be shown.

scholarly journals Molecular docking study of the phytol and its derivatives against COX-2 induced inflammation: A combined density functional study

2020 ◽  
pp. 1-5
Author(s):  
Muhammad Torequl Islam ◽  
Pranta Ray ◽  
Abul Bashar Ripon Khalipha ◽  
SM Hafiz Hassan ◽  
Md. Roich Khan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Density Functional ◽  
Chemical Reactivity ◽  
Docking Study ◽  
Functional Study ◽  
Molecular Docking Study ◽  
Study Results ◽  
Homo And Lumo ◽  
Cox 2

This study aimed to determine the activity of PYT and its derivatives against COX-2, including 5IKR protein induced inflammation by using the computational tools. PYT and its derivatives have been designed by utilizing density functional theory (DFT) and the performance of the drugs was also evaluated by molecular docking study. Results suggest that the NH2 derivative of PYT (D-NH2) showed binding energy -6.4 (Kcal/mol) with protein 5IKR of COX-2 compared to the main drug (D) that showed binding energy -5.1 (Kcal/mol) with the same protein. HOMO and LUMO energy values were also calculated to determine the chemical reactivity of all the modified drugs. Non-covalent interactions of PYT and its derivatives were essential in improving the performance. In conclusion, D-NH2 showed better preference in inhibiting to the protein 5IKR of COX-2 compared to other modified drugs and it can be claimed that D-NH2 will be the best conformer for COX-2 induced inflammation.

scholarly journals Platelet malondialdehyde production and aggregation responses induced by arachidonate, prostaglandin-G2, collagen, and epinephrine in 12 patients with storage pool deficiency

Blood ◽  
1981 ◽  
Vol 58 (1) ◽  
pp. 27-33
Author(s):  
HJ Weiss ◽  
B Lages
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Adenosine Diphosphate ◽  
Synthetic Pathway ◽  
Dense Granules ◽  
Storage Pool ◽  
Increased Sensitivity

We assessed the integrity of the prostaglandin synthetic pathway by measuring malondialdehyde (MDA) production and studied platelet aggregation responses to arachidonic acid and PGG2 in 12 patients with storage pool deficiency (SPD). Eight patients were deficient only in dense granules (delta-SPD) and four were deficient in both dense and alpha-granules (alpha delta-SPD). Production of MDA in response to arachidonic acid (AA), epinephrine, and collagen suggested that the transformation of AA to prostaglandin metabolites was normal in delta- SPD but abnormal in alpha delta-SPD and that the liberation of AA from phospholipids were abnormal in the majority of patients with SPD. Since the content of secretable adenosine diphosphate (ADP) is diminished in SPD platelets, the aggregation responses of these platelets to AA and PGG2 were studied to help answer the question whether these agents aggregate platelets directly or through release of endogenous ADP. Among patients with delta-SPD, aggregation by both AA and PGG2 was decreased in four albinos whose platelets were markedly deficient in ADP. In contrast, normal, or less strikingly abnormal, responses were observed in patients whose platelets either contained higher levels of platelet ADP or showed increased sensitivity to ADP. The more marked impaired responses to AA and PGG2 in patients with alpha delta-SPD suggest that substances derived from alpha-granules may also play a role in platelet aggregation by these agents. The aggregation responses in these patients with various types of SPD is consistent with a theory that granule-derived ADP mediates platelet aggregation by AA and PGG2.

Sign in / Sign up

Export Citation Format

Share Document