Anticancer Activity of Quinoline Derivatives; An Overview (original) (raw)
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Comprehensive review on current developments of quinoline-based anticancer agents
Arabian Journal of Chemistry, 2016
Among heterocyclic compounds, quinoline scaffold has become an important construction motif for the development of new drugs. Quinoline and its derivatives possess many types of biological activities and have been reported to show significant anticancer activity. Quinoline compounds play an important role in anticancer drug development as they have shown excellent results through different mechanism of action such as growth inhibitors by cell cycle arrest, apoptosis, inhibition of angiogenesis, disruption of cell migration and modulation. A number of quinoline derivatives have been reported till date for their anticancer activity. The present review, summarizes various mono-, di-, tri-, tetra-and heterocyclic substituent quinoline derivatives with potential anticancer activity. Their mechanism of action and possible structure activity relationship has also been discussed.
Journal of Biochemical and Molecular Toxicology, 2018
Due to a great deal of biological activities, quinoline derivatives have drawn attention for synthesis and biological activities in the search for new anticancer drug development. In this work, a variety of substituted (phenyl, nitro, cyano, N-oxide, and methoxy) quinoline derivatives (3-13) were tested in vitro for their biological activity against cancer cell lines, including rat glioblastoma (C6), human cervical cancer cells (HeLa), and human adenocarcinoma (HT29). 6-Bromo-5-nitroquinoline (4), and 6,8-diphenylquinoline (compound 13) showed the greatest antiproliferative activity as compared with the reference drug, 5-fluorouracil (5-FU), while the other compounds showed low antiproliferative activity. 6-Bromo-5-nitroquinoline (4) possesses lower cytotoxic activity than 5-FU in HT29 cell line. Due to its the apoptotic activity 6-Bromo-5-nitroquinoline (4) has the potential to cause cancer cell death.
A new and potent class of quinoline derivatives against cancer
Monatshefte für Chemie - Chemical Monthly, 2015
A new class of 4-quinolinylhydrazone derivatives has been synthesized and evaluated for their cytotoxic potential against three cancer cell lines using the MTT assay. Compounds displaying more than 90 % of growth inhibition were evaluated for in vitro anticancer activities against four human cancer cell lines. The results were expressed as the concentrations that induce 50 % inhibition of cell growth (IC 50) in lg/cm 3. These compounds exhibited good cytotoxic activity against at least three cancer cell lines, with IC 50 values between 0.314 and 4.65 lg/ cm 3. These derivatives are useful starting points for further study for new anticancer drugs and confirm the potential of quinoline derivatives as lead compounds in anticancer drug discovery.
Pharmaceuticals, 2021
A new series of 2,4-disubstituted benzo[g]quinoxaline molecules have been synthesized, using naphthalene-2,3-diamine and 1,4-dibromonaphthalene-2,3-diamine as the key starting materials. The structures of the new compounds were confirmed by spectral data along with elemental microanalyses. The cytotoxic activity of all synthesized benzo[g]quinoxaline derivatives was assessed in vitro against the breast MCF-7 cancer cell line. The tested molecules revealed good cytotoxicity toward the breast MCF-7 cancer cell line, especially compound 3. The results of topoisomerase IIβ inhibition assay revealed that compound 3 exhibits potent inhibitory activity in submicromolar concentration. Additionally, compound 3 was found to cause pre-G1 apoptosis, and slightly increase the cell population at G1 and S phases of the cell cycle profile in MCF-7 cells. Finally, compound 3 induces apoptosis via Bax activation and downregulation of Bcl2, as revealed by ELISA assay.
Design, synthesis, and docking study of new quinoline derivatives as antitumor agents
Archiv der Pharmazie, 2019
New quinolines substituted with various heterocycles and chalcone moieties were synthesized and evaluated as antitumor agents. All the synthesized compounds were in vitro screened against 60 human cancer cell lines. Compound 13 showed the highest cytotoxicity toward 58 cell lines, exhibiting distinct growth inhibition values (GI 50) against the majority of them, including SR, HL-60 (TB) strains (leukemia), and MDA-MB-435 strains (melanoma), with GI 50 values of 0.232, 0.260, and 0.300 µM, respectively. It exhibited great selectivity toward cancer cell lines, with less toxic effect against normal cells represented by skin fibroblast (BJ) and breast epithelial cell lines (MCF-10F). The enzyme inhibitory activity of compound 13 was evaluated against topoisomerase 1 (Topo 1), epidermal growth factor receptor and vascular endothelial growth factor receptor 2, where it displayed worthy Topo 1 inhibition activity with an IC 50 value of 0.278 µM compared with camptothecin as a reference drug (IC 50 0.224 µM). Docking studies were performed to investigate the recognition profile of compound 13 with the Topo 1 enzyme binding site.
Synthesis of New Quinoline Derivatives as Inhibitors of Human Tumor Cells Growth
Archiv der Pharmazie, 2010
A series of new 8-[(2H-tetrazol-5-yl)methoxy]quinoline derivatives, their sugar hydrazones, and their Nglycoside derivatives were synthesized. Furthermore, the 1,2,4-triazole-3-one derivatives 3 and 4 were synthesized from the amidrazone derivative 2. Some of the newly prepared compounds demonstrated inhibitory effects on the growth of MCF-7 human breast cancer cells as compared with the activity of the commonly used anticancer drug, cisplatin. The results of antitumor evaluation revealed that compounds 2-5, 8b, and 12 inhibited the growth of cancer cells through their effect as free-radical regulators by increasing the activity of superoxide dismutase and depletion of intracellular levels of reduced glutathione, catalase and glutathione peroxidase activities, accompanied with a high production of hydrogen peroxide, nitric oxide, and other free radicals causing the killing of tumor cells. The results suggested that the prepared compounds possess significant anticancer activity comparable to cisplatin and the antitumor activity of these prepared compounds was accompanied with a reduction in the levels of protein and nucleic acids.
A Review on Synthesis of Quinoline Analogs as Antimalarial, Antibacterial and Anticancer agents
2021
Numerous natural products possessing quinoline moiety exhibit interesting biological and pharmacological properties, such as antimalarial, antibacterial, antiasthmatic, antihypertensive, anti-inflammatory, immunosuppressive, antileishmanial, and anticancer activity. Surprising, quinoline scaffold has been used to synthesize antimalarial, antibacterial and anticancer drugs. This article provides update on the latest development in synthesis and biological evaluation of antimalarial, antibacterial and anticancer quinoline analogs. The new synthetic methodologies and the biological activities of the new quinoline analogs in the three areas were focused. Key words: antimalarial, antibacterial, anticancer and quinoline
Synthesis and in vitro antitumor activity of new quinoxaline derivatives
European journal of medicinal chemistry, 2009
A series of novel 5,7-diamino-3-phenyl-2-benzylamino, 2-phenoxy, and 2-thiophenyl substituted quinoxalines has been designed, synthesized and evaluated for their in vitro antitumor activity towards cell lines of nine different types of human cancers. Some of these compounds exhibited inhibitory effects on the growth of a wide range of cancer cell lines generally at 10(-6) M, in some cases at 10(-7) M and 10(-8) M concentrations. Within this series the benzylamino quinoxaline derivatives 1b-7b were the most active, whereas compound 2c showed the highest MG_MD value (-5.66).
Anti-breast cancer activity of some novel quinoline derivatives
Acta Pharmaceutica, 2015
To discover new bioactive lead compounds for medicinal purposes, 2-cyano-3-(4-substituted)-N-(quinolin-3-yl) acrylamide derivatives 2–24, chromenes 25, 26 and benzochromenes 27, 28 were synthesized. The structures of the newly synthesized compounds were confirmed by elemental analyses, IR, 1H NMR and 13C NMR spectroscopies. In addition, the structure of compound 1 was confirmed through X-ray crystallography. All the newly synthesized compounds were evaluated for their cytotoxic activity against the breast cancer cell line MCF7. The corresponding 2-cyano-3-(4-hydroxy-3-methoxyphenyl)-N-(quinolin-3-yl) acrylamide (15), 3-oxo-N-(quinolin-3-yl)-3H-benzol[f] chromene-2-carboxamide (27), 2-cyano-3-(4-fluorophenyl-N-(quinolin-3-yl) acrylamide (7), 2-cyano-5-(4-(dimethyl-amino) phenyl)-N-(quinolin-3-yl) penta-2,4-dienamide (19) exhibited higher activity compared to doxorubicin (with IC 50 value of 47.9 μmol L−1) as a reference drug, with IC 50 values of 29.8, 39.0, 40.0, 40.4 μmol L−1, resp...
New arylated benzo[h]quinolines induce anti-cancer activity by oxidative stress-mediated DNA damage
Scientific Reports, 2016
The anti-cancer activity of the benzo[h]quinolines was evaluated on cultured human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The inhibitory effect of these compounds on the cell growth was determined by the MTT assay. The compounds 3e, 3f, 3h and 3j showed potential cytotoxicity against these human cancer cell lines. Effect of active compounds on DNA oxidation and expression of apoptosis related gene was studied. We also developed a quantitative method to measure the activity of cyclin-dependent kinases-2 (CDK2) by western blotting in the presence of active compound. In addition, molecular docking revealed that benzo[h]quinolines can correctly dock into the hydrophobic pocket of the targets receptor protein aromatase and CDK2, while their bioavailability/drug-likeness was predicted to be acceptable but requires future optimization. These findings reveal that benzo[h]quinolines act as anti-cancer agents by inducing oxidative stressmediated DNA damage. Cancer remains a major health problem worldwide with significant morbidity and mortality rates, causing about 14.6% of all worldwide deaths 1. Currently, radio and chemotherapy are used for cancer treatment. In many cases these are successful, while in some cases they lead to severe compromising of the immune system due to lack of cell selectivity 2. The treatment of cancer is indeed associated with many side effects, which include mutagenicity, tumorigenicity, skin irritation, developmental toxicity, hepatotoxicity, drug-induced cancer, alopecia etc resulting in a strong need for novel anti-cancer agents. In the last decade, several quinoline analogues have been shown to have anti-cancer activity. The quinoline ring system and its fused derivatives are significant structural units and are found in various alkaloids, therapeutics and synthetic analogues, which exhibit diverse biological activities 3-5. Various quinolines have been reported as anti-malarial, anti-inflammatory, anti-asthmatic, anti-bacterial, anti-hypertensive and platelet derived growth factor receptor tyrosine kinase (PDGF-RTK)-inhibiting agents 6. A large variety of quinolines are reported to exhibit substantial anti-cancer activity 7-14 through a variety of mechanisms, such as cell cycle arrest in the G2 phase 13 , inhibition of topoisomerase 15 , inhibition of tubulin polymerization 16 and the inhibition of tyrosine kinases 17-19. Herein, we are reporting the anti-cancer activity of ten benzo[h]quinoline derivatives against human skin cancer (G361), lung cancer (H460), breast cancer (MCF7) and colon cancer (HCT116) cell lines. The most potent compounds identified (3e, 3f, 3h and 3j) showed effective cytotoxicity against these cancer cell lines with IC 50 values ranging from 4.7 to 7.6 μ M. Molecular docking studies were also performed to predict the likely interactions