naphthoquinones and coumarin

In current study, a series of shikonin derivatives were synthesized and its anticancer activity was evaluated. As a result, PMMB232 showed the best antiproliferation activity with an IC

Topics: Antineoplastic Agents; Apoptosis; Carboxylic Acids; Coumarins; Drug Evaluation, Preclinical; Female; HeLa Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Molecular Docking Simulation; Naphthoquinones; Uterine Cervical Neoplasms

We evaluated the skin sensitizing potential of 10 natural organic chemicals, or their derivatives, which are included in foods and/or skin products, using a modified local lymph node assay (LLNA), with an elicitation phase (LLNA:DAE). The following compounds were tested: carminic acid, esculetin, 4-methyl esculetin, coumarin, quercetin, curcumin, naringenin, chlorogenic acid, isoscopoletin, and shikonin. Esculetin, 4-methyl esculetin, isoscopoletin, and shikonin yielded positive results. In particular, shikonin at a very low concentration (0.05%) induced an elicitation response. In conclusion, four of the 10 natural organic chemicals tested had a skin sensitization potential, with shikonin producing serious reaction even at a very low concentration.

Topics: Animals; Carmine; Cosmetics; Coumarins; Curcumin; Dose-Response Relationship, Drug; Female; Food Analysis; Local Lymph Node Assay; Mice, Inbred CBA; Naphthoquinones; Quercetin; Skin; Skin Irritancy Tests; Umbelliferones

Based on previous Topoisomerase II docking studies of naphthoquinone derivatives, a series of naphthoquinone-coumarin conjugates was synthesized through a multicomponent reaction from aromatic aldehydes, 4-hydroxycoumarin and 2-hydroxynaphthoquinone. The hybrid structures were evaluated against the α isoform of human topoisomerase II (hTopoIIα), Escherichia coli DNA Gyrase and E. coli Topoisomerase I. All tested compounds inhibited the hTopoIIα-mediated relaxation of negatively supercoiled circular DNA in the low micromolar range. This inhibition was specific since neither DNA Gyrase nor Topoisomerase I were affected. Cleavage assays pointed out that naphthoquinone-coumarins act by catalytically inhibiting hTopoIIα. ATPase assays and molecular docking studies further pointed out that the mode of action is related to the hTopoIIα ATP-binding site.

Topics: Coumarins; DNA Topoisomerases, Type II; Dose-Response Relationship, Drug; Humans; Molecular Structure; Naphthoquinones; Structure-Activity Relationship; Topoisomerase II Inhibitors

Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation by regulating CDK/cyclin complexes. Overexpression of these enzymes is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, targeting CDC25 by compounds, able to inhibit their activity, appears a good therapeutic approach. Here, we describe the synthesis of a new inhibitor (SV37) whose structure is based on both coumarin and quinone moieties. An analytical in vitro approach shows that this compound efficiently inhibits all three purified human CDC25 isoforms (IC50 1-9 µM) in a mixed-type mode. Moreover, SV37 inhibits growth of breast cancer cell lines. In MDA-MB-231 cells, reactive oxygen species generation is followed by pCDK accumulation, a mark of CDC25 dysfunction. Eventually, SV37 treatment leads to activation of apoptosis and DNA cleavage, underlining the potential of this new type of coumarin-quinone structure.

Topics: Apoptosis; Benzoquinones; Breast Neoplasms; cdc25 Phosphatases; Cell Line, Tumor; Cell Proliferation; Coumarins; Cyclin-Dependent Kinases; DNA Cleavage; Female; Humans; MCF-7 Cells; Naphthoquinones; Protein Isoforms; Reactive Oxygen Species; Viral Proteins

  Human cytochrome P450 CYP2A6 and CYP2A13 catalyze nicotine metabolisms and mediate activation of tobacco-specific carcinogens including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL). In this study, we found rhinacanthins A, B, and C isolated from Rhinacanthus nasutus potentially inhibited coumarin 7-hydroxylation mediated by reconstituted purified recombinant CYP2A6 and CYP2A13. Rhinacanthins A-C are mechanism-based inactivators of CYP2A6 and CYP2A13 as they cause concentration, time and NADPH-dependent inhibition. Among the three rhinacanthins, rhinacanthin-B possessed highest inhibitory potency against CYP2A13 with apparent KI and kinact of 0.16 µM and 0.1 min(-1), respectively, while values of 0.44 µM and 0.12 min(-1) were found against CYP2A6. Rhinacanthin-C had least inhibition potency, with apparent KI and kinact of 0.97 µM and 0.07 min(-1) for CYP2A6, respectively, and values of 1.68 µM and 0.05 min(-1) for CYP2A13. Rhinacanthin-A inhibited CYP2A6 and CYP2A13 with apparent KI values of 0.69 and 0.42 µM, respectively and apparent kinact of 0.18 and 0.06 min(-1), respectively. The inhibition of both enzymes by rhinacanthins A-C could not be prevented by addition of trapping agents or reversed by dialysis or potassium ferricyanide. These findings demonstrated that rhinacanthins A-C, which are 1,4-naphthoquinone derivatives, irreversibly inhibited CYP2A6 and CYP2A13 in a mechanism-based inhibition mode.

Topics: Acanthaceae; Animals; Aryl Hydrocarbon Hydroxylases; Coumarins; Cytochrome P-450 CYP2A6; Humans; Hydroxylation; Kinetics; NADPH-Ferrihemoprotein Reductase; Naphthoquinones; Plant Extracts; Rats; Recombinant Proteins

Topics: Amino Acids; Aminoisobutyric Acids; Antimetabolites; Carbon Isotopes; Coumarins; Factor VII; Glycine; In Vitro Techniques; Liver; Metabolism; Naphthoquinones; Pharmacology; Proteins; Rats; Research; Ubiquinone; Vitamin K; Warfarin

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Heparin Antagonists; Humans; Hypoprothrombinemias; Naphthoquinones; Prothrombin; Retinoids; Vitamin K; Vitamin K 1

Topics: Coumarins; Esters; Naphthoquinones

Topics: Antifibrinolytic Agents; Coumarins; Hemorrhage; Humans; Naphthoquinones; Phenprocoumon; Retinoids; Vitamin K; Vitamin K 1

Topics: Animals; Antifibrinolytic Agents; Behavior, Animal; Coumarins; Humans; Naphthoquinones; Phenprocoumon; Vitamin K

Topics: Antifibrinolytic Agents; Coumarins; Ethyl Biscoumacetate; Heparin Antagonists; Naphthoquinones; Phenindione; Thromboembolism; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Hemorrhage; Naphthoquinones; Poisoning; Retinoids; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Cardiovascular Agents; Coumarins; Hexylresorcinol; Humans; Muscle Relaxants, Central; Naphthoquinones; Rosaniline Dyes; Vitamin K

Topics: Antidotes; Antifibrinolytic Agents; Coumarins; Heparin Antagonists; Naphthoquinones; Retinoids; Vitamin K; Vitamin K 1

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Hemorrhagic Disorders; Heparin Antagonists; Hypoprothrombinemias; Naphthoquinones; Vitamin K; Vitamin K 1; Vitamin K 3

Topics: 4-Hydroxycoumarins; Antifibrinolytic Agents; Coumarins; Heparin Antagonists; Humans; Naphthoquinones; Retinoids; Rodenticides; Vitamin K; Vitamins

Topics: Anticoagulants; Antifibrinolytic Agents; Coumarins; Dicumarol; Ethyl Biscoumacetate; Hemostatics; Heparin Antagonists; Humans; Naphthoquinones; Phenindione; Prothrombin; Vitamin K

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Hemostatics; Humans; Hypoprothrombinemias; Naphthoquinones; Prothrombin; Retinoids; Vitamin K; Vitamin K 1; Vitamin K 2

Topics: Antidotes; Antifibrinolytic Agents; Coumarins; Dicumarol; Heparin Antagonists; Naphthoquinones; Prothrombin; Retinoids; Vitamin K; Vitamins

Topics: Antifibrinolytic Agents; Coumarins; Dicumarol; Ethyl Biscoumacetate; Hypoprothrombinemias; Naphthoquinones; Prothrombin; Vitamin K

Topics: Administration, Intravenous; Antifibrinolytic Agents; Coumarins; Dicumarol; Emergencies; Emulsions; Naphthoquinones; Prothrombin; Vitamin K; Vitamin K 1

Topics: Antidotes; Antifibrinolytic Agents; Coumarins; Dicumarol; Humans; Naphthoquinones; Vitamin K; Vitamins