Anthranilamides with quinoline and β-carboline scaffolds: design, synthesis, and biological activity
| Autor: | Maja Beus, Leentje Persoons, Dirk Daelemans, Dominique Schols, Kirsi Savijoki, Pekka Varmanen, Jari Yli-Kauhaluoma, Kristina Pavić, Branka Zorc |
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| Rok vydání: | 2021 |
| Předmět: |
Biochemistry & Molecular Biology
Chemistry Multidisciplinary INHIBITION Quinoline Chemistry Medicinal Adenocarcinoma Quorum sensing (QS) inhibition Antiviral Agents ARTEMISININ Catalysis Inorganic Chemistry TRANILAST HARMINE DERIVATIVES Drug Discovery Humans ortho-Aminobenzoates Pharmacology & Pharmacy DRUG Physical and Theoretical Chemistry Antiviral Molecular Biology CHLOROQUINE Science & Technology VIVO ANTITUMOR ACTIVITIES beta-Carboline Organic Chemistry Chloroquine IN-VITRO General Medicine Amides Anthranilamide · Quinoline β-Carboline Anticancer RESAZURIN L. SEEDS EXTRACT Anti-Bacterial Agents Chemistry Applied Pancreatic Neoplasms Chemistry Physical Sciences Quinolines Original Article Life Sciences & Biomedicine Information Systems Carbolines |
| Zdroj: | Molecular Diversity |
| ISSN: | 1573-501X |
| Popis: | Graphical abstract In the present study, we report the design and synthesis of novel amide-type hybrid molecules based on anthranilic acid and quinoline or β-carboline heterocyclic scaffolds. Three types of biological screenings were performed: (i) in vitro antiproliferative screening against a panel of solid tumor and leukemia cell lines, (ii) antiviral screening against several RNA viruses, and (iii) anti-quorum sensing screening using gram-negative Chromobacterium violaceum as the reporter strain. Antiproliferative screening revealed a high activity of several compounds. Anthranilamides 12 and 13 with chloroquine core and halogenated anthranilic acid were the most active agents toward diverse cancer cell lines such as glioblastoma, pancreatic adenocarcinoma, colorectal carcinoma, lung carcinoma, acute lymphoblastic, acute myeloid, chronic myeloid leukemia, and non-Hodgkin lymphoma, but also against noncancerous cell lines. Boc-protected analogs 2 and 3 showed moderate activities against the tested cancer cells without toxic effects against noncancerous cells. A nonhalogenated quinoline derivative 10 with N-benzylanthranilic acid residue was equally active as 12 and 13 and selective toward tumor cells. Chloroquine and quinoline anthranilamides 10–13 exerted pronounced antiviral effect against human coronaviruses 229E and OC43, whereas 12 and 13 against coronavirus OC43 (EC50 values in low micromolar range; selectivity indices from 4.6 to > 10.4). Anthranilamides 14 and 16 with PQ core inhibited HIV-1 with EC50 values of 9.3 and 14.1 µM, respectively. Compound 13 displayed significant anti-quorum/biofilm effect against the quorum sensing reporter strain (IC50 of 3.7 μM) with no apparent bactericidal effect. Supplementary Information The online version contains supplementary material available at 10.1007/s11030-021-10347-8. |
| Databáze: | OpenAIRE |
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