ascorbic-acid and coumarin

Coumarin and benzimidazole are privileged structures in medicinal chemistry and are widely used in drug discovery and development due to their vast biological properties. The pharmacokinetic and pharmacodynamic properties of the individual scaffolds can be improved by developing coumarin-benzimidazole chimeric molecules via molecular hybridization approach. The three major classes of coumarin-benzimidazole hybrids are merged, fused and spacer-linked hybrids. Depending on the substitution position, fused hybrids and spacer-linked hybrids can be further classified as coumarin-C3 hybrids, coumarin-C4 hybrids and coumarin-C5/6/7/8 hybrids. Most of the coumarin-benzimidazole hybrid molecules exhibited potent anticancer, antiviral, antimicrobial, antitubercular, anthelmintic, anti-inflammatory, antioxidant, anticonvulsant and carbonic anhydrase inhibitory activities. The fused coumarin-C3 hybrid (2), thiomethylene-linked coumarin-C3 hybrid (45), N-glucoside substituted thiomethylene-linked coumarin-C3 hybrid (37c), amide-linked coumarin-C3 hybrid (50a), and sulfonylmethylene-linked coumarin-C4 hybrid (63) were identified as the representative potent anticancer, antimicrobial, antiviral, antioxidant and antitubercular agents respectively. The biological properties of the different classes of coumarin-benzimidazole hybrids with their structure-activity relationship studies and the mechanism of action studies were presented in this review, aiming to help the researchers across the globe to generate future hybrid molecules as potential drug candidates.

Topics: Anti-Infective Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Benzimidazoles; Chemistry, Pharmaceutical; Coumarins; Drug Development; Humans; Molecular Structure

A series of hybrids of hydroxypyridinone and coumarin were rationally designed, synthesized and biologically evaluated for their iron ion chelating and MAO-B inhibitory activities. Most of the compounds displayed excellent iron ion chelating effects and moderate to good anti-MAO-B activities. Compound 27a exhibited the most potent activity against MAO-B, with an IC

Topics: Alzheimer Disease; Animals; Cell Line, Tumor; Cell Survival; Coumarins; Dose-Response Relationship, Drug; Drug Design; Humans; Hydrogen Peroxide; Iron Chelating Agents; Mice; Mice, Inbred ICR; Molecular Docking Simulation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Pyridines; Scopolamine; Structure-Activity Relationship

A novel series of coumarin-lipoic acid conjugates were synthesized via cycloaddition click reaction to find out new multi-target-directed ligands (MTDLs) for treatment of Alzheimer's disease (AD). All of synthesized compounds were screened for neuroprotective and anti-cholinesterase activities. Based on primary screening, two compounds (5 and 11) were subjected to further biological evaluations. In particular, compound 11 which was the most potent AChE inhibitor showed good inhibitory effect on Aβ-aggregation and intracellular ROS (reactive oxygen species) formation, as well as the ability of selective bio-metal chelation and neuroprotection against H

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cell Survival; Cholinesterase Inhibitors; Cholinesterases; Coumarins; Dose-Response Relationship, Drug; Drug Design; Humans; Hydrogen Peroxide; Ligands; Molecular Docking Simulation; Molecular Structure; PC12 Cells; Protein Aggregates; Rats; Reactive Oxygen Species; Structure-Activity Relationship; Thioctic Acid

A series of novel coumarin pyrazole hybrids of biological interest were synthesized from the hydrazones, carbazones and thiocarbazones via Vilsmeier Haack formylation reaction. These intermediates and formyl pyrazoles were evaluated for antimicrobial and antioxidant activities. Among the series, compounds 6g and 6h showed excellent antimicrobial activity against different bacterial and fungal strains and compounds 7g, 7h were found to be potent antioxidant agents in both DPPH and hydroxyl radical scavenging assays. Further, detailed quantitative structure-activity relationship (QSAR) analysis indicated the molecular parameters that contribute to increased potency of inhibition. The above findings would further encourage our understanding in employing coumarin pyrazole hybrids as potential antibiotic agents for treating infections caused by pathogenic microbes and fungi. Further, it also paves the way for exploration of these compounds as potential therapeutic agents to treat conditions arising because of excessive oxidative damage.

Topics: Anti-Infective Agents; Antioxidants; Bacteria; Bacterial Infections; Coumarins; Fungi; Humans; Microbial Sensitivity Tests; Mycoses; Pyrazoles; Quantitative Structure-Activity Relationship

In present work we have designed and synthesized total twelve novel 3-(3-(1H-indol-3-yl)-3-phenylpropanoyl)-4-hydroxy-2H-chromen-2-one derivatives 13(a-l) using Ho(3+) doped CoFe2O4 nanoparticles as catalyst and evaluated for their potential antileishmanial and antioxidant activities. The compounds 13a, 13d and 13h were found to possess significant antileishmanial activity (IC50 value=95.50, 95.00 and 99.00μg/mL, respectively) when compared to the standard sodium stibogluconate (IC50=490.00 μg/mL). The compounds 13a (IC50=12.40 μg/mL), 13d (IC50=13.49 μg/mL), 13g (IC50=13.24 μg/mL) and 13l (IC50=13.74 μg/mL) had shown good antioxidant activity when compared with standards butylated hydroxy toluene (IC50=16.5 μg/mL) and ascorbic acid (IC50=12.8 μg/mL). After performing molecular docking studies, it was found that compounds 13a and 13d had potential to inhibit pteridine reductase 1 enzyme. In silico ADME pharmacokinetic parameters had shown promising results and none of the synthesized compounds had violated Lipinski's rule of five. Thus, suggesting that compounds from the present series can serve as important gateway for the design and development of new antileishmanial as well as antioxidant agent.

Topics: Antioxidants; Antiprotozoal Agents; Binding Sites; Cell Survival; Coumarins; Drug Design; Enzyme Inhibitors; HeLa Cells; Humans; Inhibitory Concentration 50; Leishmania; Molecular Docking Simulation; Oxidoreductases; Protein Structure, Tertiary; Protozoan Proteins; Structure-Activity Relationship

A series of novel 1-(4-methylcoumarinyl-7-oxyacetyl)-3,5-dimethyl-4(arylazo)pyrazoles and 1-(4-methylcoumarinyl-7-oxyacetyl)-3-methyl-4-(substituted phenyl) hydrazono-2-pyrazolin-5-ones were synthesised and evaluated for antibacterial and antioxidant activities. Compounds 3b, 3g, 5b, 5d and 5g showed good antibacterial activity and compound 5e was found to be the most active antioxidant in the series, and thus represent a new class of promising lead compounds.

Topics: Anti-Bacterial Agents; Antioxidants; Bacillus subtilis; Coumarins; Free Radical Scavengers; Pyrazoles; Pyrazolones; Staphylococcus aureus; Structure-Activity Relationship

Human lymphoid cells (Raji) were exposed to water-soluble compounds from cigarette smoke (CS) generated in a smoking machine. DNA damage, as detected by alkaline single-cell microelectrophoresis (COMET assay), was induced in a time- and concentration-dependent manner in the cells. Most of the rapidly induced DNA damage was attributable to direct-acting compounds since cytochrome P450-related metabolic activities (ethoxy- and pentoxyresorufin-O-deethylases and coumarin-7-hydroxylase) were absent or very low. In addition, induction of DNA damage could be inhibited only slightly by beta-naphthoflavone and coumarin. Vitamin C enhanced DNA damage in Raji cells probably by redox cycling of catechol and hydroquinone present in CS implicating reactive oxygen intermediates as another source of DNA damage. N-acetylcysteine, a radical scavenger and glutathione precursor, reduced DNA damage in Raji cells when exposure to CS was followed by 2 h post-incubation in culture medium. Unrepaired DNA damage caused by CS persisted longer than gamma-irradiation-induced DNA damage. Among the CS constituents, acrolein, but not formaldehyde and acetaldehyde, induced DNA damage although less intensely than CS itself. At 50 and 100 microM concentrations, acrolein also inhibited repair of gamma- irradiation-induced DNA damage in the COMET assay. Inhibition of DNA synthesis by acrolein at 50 microM was demonstrated by an immunochemical assay for bromo-deoxyuridine incorporation; however, inhibition of a representative repair enzyme, 8-oxoguanosine hydrolase, by either CS or acrolein was not observed. The present results further confirm the presence of direct-acting genotoxic components and inhibitors of DNA repair in the gas phase of tobacco smoke, that may contribute to DNA damage and smoking-associated cancers of the upper aerodigestive tract.

Topics: Acetaldehyde; Acetylcysteine; Acrolein; Aldehydes; Aryl Hydrocarbon Hydroxylases; Ascorbic Acid; B-Lymphocytes; beta-Naphthoflavone; Biotransformation; Burkitt Lymphoma; Coumarins; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2A6; Cytochrome P-450 CYP2B1; Cytochrome P-450 Enzyme System; DNA Damage; DNA Repair; DNA-Formamidopyrimidine Glycosylase; DNA, Neoplasm; Formaldehyde; Free Radical Scavengers; Gamma Rays; Humans; Mixed Function Oxygenases; N-Glycosyl Hydrolases; Oxidation-Reduction; Reactive Oxygen Species; Smoke

Sodium vanadate inhibits the oxidative demethylation of substrates of the cytochrome P-450-dependent monooxygenase system in vivo in mice. [14C]Methacetin and 7-[methoxy-14C] coumarin were used as substrates, and the exhaled 14CO2 was monitored using the technique of the breath test. The inhibition is of short duration and begins to subside after about 10 min. The inhibition is dose-dependent; half-maximal effect is achieved at a dose of approximately 60 mumol/kg. The inhibition pattern is identical for both substrates, although 62% of the label of [14C] methacetin and only 10% of 7-[methoxy-14C] coumarin are enhaled within 1 h. Pretreatment with ascorbic acid (50 mg/kg p.o.) drastically diminishes the observed inhibitory effect of vanadate. Similarly, application of an equimolar dose of vanadyl sulphate produces a comparatively weak retardation of 14CO2 exhalation. The effect of vanadate is thought to occur by its competition for electrons normally transferred to cytochrome P-450.

Topics: Acetamides; Animals; Ascorbic Acid; Breath Tests; Carbon Dioxide; Coumarins; Cytochrome P-450 Enzyme Inhibitors; Dealkylation; Liver; Male; Mice; Oxidation-Reduction; Substrate Specificity; Vanadium

Inhibition in vitro of human red blood cell glyoxalase I activity was measured by the decrease in the rate of formation of S-D-lactoyl-glutathione as determined by the change in absorbance at 240 nm. The percentage activity remaining was determined after addition of various potential inhibitor compounds and the concentration for 50% activity was obtained by graphical interpolation. The inhibitors were selected on the basis of their similarity to a possible transition-state enediol intermediate of methylglyoxal. The most effective inhibitors were dihydroxycoumarins with a 50% inhibition of 0.03 mM. Inhibition of methylglyoxal catabolism suggests possible application as chemotherapeutic agents based on the inhibitor characteristics of methylglyoxal.

Topics: Ascorbic Acid; Coumarins; Erythrocytes; Esculin; Humans; In Vitro Techniques; Lactoylglutathione Lyase; Lyases; Tryptophan

Topics: Ascorbic Acid; Capillaries; Cardiovascular System; Coumarins; Ethyl Biscoumacetate; Inositol; Vitamins

Topics: Abscess; Ascorbic Acid; Coumarins; Humans; Meningitis; Palatine Tonsil; Penicillins; Peritonsillar Abscess; Sepsis; Sinus Thrombosis, Intracranial; Streptomycin; Sulfonamides; Vitamin B Complex

Topics: Ascorbic Acid; Coumarins; Female; Flavonoids; Genitalia; Genitalia, Female; Gynecology; Humans; Obstetrics; Postpartum Period; Thrombosis; Venous Thrombosis; Vitamin E; Vitamins

Topics: Adrenal Glands; Ascorbic Acid; Carbohydrate Metabolism; Coumarins; Dicumarol; Liver

Topics: Adenosine Triphosphate; Ascorbic Acid; Bile Acids and Salts; Coumarins; Diet; Folic Acid; Heparin; Humans; Hypnotics and Sedatives; Khellin; Magnesium Sulfate; Myocardial Infarction; Purines; Quinidine; Salts; Sympathomimetics; Vitamin B Complex; Vitamin E; Vitamins