Synthesis, Antiviral and Kinesin Eg5 Activities of New Indomethacin Analogues
Najim A. Al-Masoudi, Dawood S. Ali
Chemical Science International Journal · pp. 516–536 · Published 3 Mar 2014
10.9734/ACSJ/2014/8721Abstract
Aim: Synthesis, characterization, anti-HIV, anti-HCV and kinesin activities of new indomethacin analogues have been carried out. Methodology: Arylated derivatives of indomethacin via the Suzuki-Miyaura cross-coupling reaction using palladium acetate/triphenylphophineor palladium based N-heterocyclic carbene (Pd-NHC) complexe as catalysts were synthesized and characterized by the 1H and 13C and 2D NMR study. Analogously, indomethacin analogues bearing thioureido and amide moieties of various L-amino acid esters were prepared via Kabbani and coupling reactions, respectively. Results: All the new analogues were evaluated In vitro for their antiviral activity against the replication of HIV-1 and HIV-2 in MT-4 cells using MTT assay. Compounds 28, 31 and 32 were evaluated In vitro for their inhibitory activity against hepatitis virus C (HCV) in the Huh 5-2 replicon system (type 1b, Con1 strain). Additionally, some analogues were screened for their inhibitory activity against the ATPase enzyme and the motor-protein Kinesin Eg5.In conclusion, Compounds 31 and 39 showed anti-HIV activity with IC50 values of >1.81 and > 3.21μM (CC50 of 3.31 and 28.89μM), resulting in selectivity indexs (SI) of 6 and 9, respectively. Conclusion: Compounds 31 and 39 displayed better anti-HIV activity than the other derivatives (SI = 6 and 9, respectively). Compound 27 showed ATPase inhibition value of 48% at 100 µM concentration.
References (44)
- 1 Isolation of a T-Lymphotropic Retrovirus from a Patient at Risk for Acquired Immune Deficiency Syndrome (AIDS) [DOI]
- 2 Detection, Isolation, and Continuous Production of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and Pre-AIDS [DOI]
- 3 3'-Azido-3'-deoxythymidine (BW A509U): an antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. [DOI]
- 4 Small Molecule Inhibitor of Mitotic Spindle Bipolarity Identified in a Phenotype-Based Screen [DOI]
- 5 Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues [DOI]
- 6 Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs. [DOI]
- 7 Gradient selection in inverse heteronuclear correlation spectroscopy [DOI]
- 8 Indomethacin and Aspirin abolish Prostaglandin Release from the Spleen [DOI]
- 9 Pharmacological analysis of cyclooxygenase-1 in inflammation [DOI]
- 10 Microtubule motors in mitosis [DOI]
- 11 Structural and Functional Basis of Cyclooxygenase Inhibition [DOI]
- 12 Microtubule-targeted anticancer agents and apoptosis [DOI]
- 13 Experiments for recording pure-absorption heteronuclear correlation spectra using pulsed field gradients [DOI]
- 14 Tetrazolium-based colorimetric assay for the detection of HIV replication inhibitors: revisited 20 years later [DOI]
- 15 In Search of a Novel Anti-HIV Drug: Multidisciplinary Coordination in the Discovery of 4-[[4-[[4-[(1 E )-2-Cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, Rilpivirine) [DOI]
- 16 Evidence that Monastrol Is an Allosteric Inhibitor of the Mitotic Kinesin Eg5 [DOI]
- 17 New Palladium Carbene Catalysts for the Heck Reaction of Aryl Chlorides in Ionic Liquids [DOI]
- 18 Cyclooxygenase-2 Biology [DOI]
- 19 Indomethacin: A New Non-steroid Anti-inflammatory Agent [DOI]
- 20 Indomethacin Has a Potent Antiviral Activity against Sars Coronavirus [DOI]
- 21 A replicon-based bioassay for the measurement of interferons in patients with chronic hepatitis C [DOI]
- 22 Novel non-nucleoside inhibitors of HIV-1 reverse transcriptase. 1. Tricyclic pyridobenzo- and dipyridodiazepinones [DOI]
- 23 Role of endothelial adhesion molecules in NSAID-induced gastric mucosal injury [DOI]
- 24 A microassay for ATPase [DOI]
- 25 The Activity of Plant-Derived Antiretroviral Proteins MAP30 and GAP31 against Herpes Simplex Virus Infectionin Vitro [DOI]
- 26 ATPase Mechanism of Eg5 in the Absence of Microtubules: Insight into Microtubule Activation and Allosteric Inhibition by Monastrol [DOI]
- 27 Indolyl esters and amides related to indomethacin are selective COX-2 inhibitors [DOI]
- 28 Respiratory Syncytial Virus (RSV) Infection Induces Cyclooxygenase 2: A Potential Target for RSV Therapy [DOI]
- 29 The 2′-Trifluoromethyl Analogue of Indomethacin Is a Potent and Selective COX-2 Inhibitor [DOI]
- 30 NSAIDs: Old Drugs Reveal New Anticancer Targets [DOI]
- 31 Type C Virus-Producing Cell Lines Derived from Adult T Cell Leukemia [DOI]
- 32 Novel mechanism of resistance to paclitaxel (Taxol) in human K562 leukemia cells by combined selection with PSC 833.
- 33 Molecular Basis of the Time-Dependent Inhibition of Cyclooxygenases by Indomethacin [DOI]
- 34 Pathway of ATP Hydrolysis by Monomeric Kinesin Eg5 [DOI]
- 35 COX inhibitors Indomethacin and Sulindac derivatives as antiproliferative agents: Synthesis, biological evaluation, and mechanism investigation [DOI]
- 36 Tenidap, a structurally novel drug for the treatment of arthritis: Antiinflammatory and analgesic properties [DOI]
- 37 Utility of MetaSite in Improving Metabolic Stability of the Neutral Indomethacin Amide Derivative and Selective Cyclooxygenase-2 Inhibitor 2-(1-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-N-phenethyl-acetamide [DOI]
- 38 Synthesis, structural characterization and cytotoxic activity of organotin derivatives of indomethacin [DOI]
- 39 Synthesis and biological evaluation of indomethacin analogs possessing a N-difluoromethyl-1,2-dihydropyrid-2-one ring system: A search for novel cyclooxygenase and lipoxygenase inhibitors [DOI]
- 40 Desmethyl Derivatives of Indomethacin and Sulindac as Probes for Cyclooxygenase-Dependent Biology [DOI]
- 41 1H- and 13C-NMR Study of Some 6,7-Dihaloquinolone Nucleosides and Their Derivatives [DOI]
- 42 Cytostatic and Antiviral Activity Evaluations of Hydroxamic Derivatives of Some Non‐steroidal Anti‐inflammatory Drugs [DOI]
- 43 Indomethacin inhibits viral RNA and protein synthesis in cells infected with vesicular stomatitis virus [DOI]
- 44 ChemInform Abstract: Novel Non‐Nucleoside Inhibitors of HIV‐1 Reverse Transcriptase. Part 1. Tricyclic Pyridobenzo‐ and Dipyridodiazepinones. [DOI]
Cited by 0
No indexed citations yet.
Related research
- Antimicrobial Profile of Selected Snake Venoms and Their Associated Enzymatic Activities — shares topic coverage
- In vitro Antiviral Activity of Nauclea latifolia Root Bark Extract Against the Respiratory Syncytial Virus — shares topic coverage
- Review on Ethno-botany, Virucidal Activity, Phytochemistry and Toxicology of Solanum genus: Potential Bio-resources for the Therapeutic Management of Covid-19 — shares topic coverage
- Aloe vera (L.) Burm. F. as a Potential Anti-COVID-19 Plant: A Mini-review of Its Antiviral Activity — shares topic coverage
- Antiviral Activity of Approved Anti-Inflammatory Drugs and Prospects for Drug Repurposing: A review — shares topic coverage
Article metrics
Real usage data collected on this platform.
0
Page views
0
PDF downloads
0
Outbound clicks
0
Citations
Views by country
Approximate, from request IP at view time — not citizenship or institution. Countries with fewer than 5 views are grouped as "Other".
No views recorded yet.
Traffic sources
Referring site, by host.
No traffic recorded yet.
Views and downloads exclude known bots/crawlers. Citations combines this platform's own DOI-resolved index with each external source's own reported total — see Cited by above for individually listed citing works. Last refreshed 0 seconds ago.