Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues (original) (raw)
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Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues
Open Journal of Medicinal Chemistry
Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. A molecular docking study was employed to investigate the binding and functional properties of 3-amino pyranoquinolinone 2a-c as anti-cancer agents. The three 3-amino pyranoquinolinone 2a-c showed an interesting ability to intercalate the DNA-topoisomerase complex and were able to obtain energetically favorable binding modes (−8.3-−7.5 kcal/mol). Compound 2c containing butyl chain superiority over the other two compounds 2a-b which appeared to be involved in arene-H interactions with the two dG13 aromatic centers. The butyl chain also appeared to be immersed into a side subpocket formed by the side chains of Asn520 and Glu522 and the backbone amide of Arg503, Gly504, Lys505 and Ile506. Hence, the 3-amino pyranoquinolinone 2c used as starting material to prepare derivatives of pyrano[3,2-c]quinolone containing 1,2,4-triazine ring 4a-b which will enhance the anti-cancer activity. Pyrano[3,2-c]quinoline-2,5-diones 2a-c and 4a-b were evaluated in vitro on cell lines Ehrlich Ascites carcinoma cells (EAC), liver cancer cell line Hep-G2 and breast cancer cell line MCF-7 for the development of novel anticancer agents. The screening results revealed that compounds 4a-b were found most active candidates as anticancer agents.
ACS Medicinal Chemistry Letters, 2018
A series of pyrano[3,2-c]quinoline based structural analogues was synthesized using one-pot multicomponent condensation between 2,4-dihydroxy-1-methylquinoline, malononitrile, and diverse un(substituted) aromatic aldehydes. The synthesized compounds were evaluated for their anti-inflammatory and cytotoxicity activity. Initially, all the compounds were evaluated for the percent inhibition of cytokine release, and cytotoxicity activity and 50% inhibitory concentrations (IC 50) were also determined. Based on the primary results, it was further studied for their ability to inhibit TNF-α production in the human peripheral blood mononuclear cells (hPBMC) assay. The screening results revealed that compound 4c, 4f, 4i, and 4j were found most active candidates of the series against both anti-inflammatory and anticancer activity. The structure−activity relationship is discussed and suggested that 3-substitution on the aryl ring at C4 position of the pyrano[3,2-c]quinolone structural motif seems to be an important position for both TNF-α and IL-6 inhibition and anticancer activity as well. However, structural diversity with electron withdrawing, electron donating, sterically hindered, and heteroaryl substitution sincerely affected both the inflammation and anticancer activities.
Medicinal Chemistry Research, 2017
A series of twelve 4-methyl-2-(2-, 3-and 4-pyridinyl)quinolines 7-9 was synthesized using modified Kametani reaction protocol and their in vitro cytotoxicity was tested against human cancer cell lines MCF-7, SKBR-3, PC3, HeLa, comparing with human dermis fibroblast as non-tumor cells. In general, these molecules displayed potent anticancer properties, but also demonstrated a narrow safe margin, as it was observed for doxorubicin. Compounds 8a, 8b, 9a and 9d showed prominent selective cytotoxicity with higher IC 50 values compared with reference drug doxorubicin in prostate carcinoma, cervical epithelial carcinoma and breast carcinoma (no overexpresses the HER2/c-erb-2 gene), respectively. The 4-methyl-2-(3pyridinyl)quinoline (8a) stands out by its low unspecific cytotoxicity (IC 50 = 476.69 μM) and highly exceptional selectivity for PC3 cells (IC 50 = 4.40 μM) as an interesting model for antitumor drugs against prostate carcinoma. Its 4pyridinyl analog 9a showed superior potency against HeLa cells (IC 50 = 0.016 μM) and an outstanding selectivity (SI = 4168.1) compared to doxorubicin (IC 50 = 3.62 µM, SI = 0.7). Analog 9d revealed potent activity (IC 50 = 0.38 µM) against breast cancer MCF-7. In silico studies are also reported. ADME profiling, in silico toxicity and drug-score data of compounds 8a and 9a resulted to be favorable compared to doxorubicin.
Due to your efforts diligent on quinoline nucleus new series containing pyrimido [4, 5-b] quinoline were synthesized via starting with the strategic 2-aminoquinoline-3-carbonitrile (2) intermediates to afford various pyrimido [4, 5-b] quinoline via cyclization with different reagents to get compounds 3-24. Compounds 3, 6, 9a, 9b, 12, 15, 16a, 16b, 17, 21 and 24 were tested for in vitro antitumor activity against human breast carcinoma (MCF-7) cell line, We found what we were hoping for where compound 6 was found the most active member (IC50= 48.54 μM) than the Doxorubicin as a reference drug with (IC50= 71.80 μM). To understand the interaction of binding sites with the target protein receptor, the docking study was performed using topoisomerase II. The results of in vitro cancer activity and docking study revealed that the synthesized compounds have potential cancer activity and can be further optimized and developed as a lead compound.
Anticancer Activity of Quinoline Derivatives; An Overview
International Journal of Pharmaceutical Sciences Review and Research
Quinoline, 1-aza naphthalene/benzo pyridine, is nitrogen containing heterocyclic nucleus which is one of the major building blocks of many synthetic drugs. Quinoline derivatives have attracted many scholars’ attention because of their wide range of pharmacological activities such as antimalarial, anticancer, anti-inflammatory, antimicrobial etc. There are so many quinoline derivatives with anticancer activities were reported in various renowned journals. In this review, an attempt is made to compile the latest updates on anticancer activity of quinoline derivatives. Quinoline derivatives plays an important role in anticancer drug development through different mechanism of action like topoisomerase I and II inhibition, proteasome inhibition, antimitotic and tubulin polymerization inhibition etc.
Arkivoc, 2004
Several pyrido[4,3-g and 3,4-g]quinoline-5,10-dione and dihydrothieno[2,3-g and 3,2g]quinoline-4,9-dione derivatives were synthesized and evaluated for their potential cytotoxic properties. A number of these compounds exhibited significant in vitro antiproliferative activity at submicromolar concentration in a preliminary evaluation for their cytotoxic activity using the MT-4 cell line. These structures represent potential scaffolds in discovery of new agents with antitumoral activity and the synthetic strategy developed could be used to prepare libraries of new derivatives by combinatorial chemistry.
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.
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.
The antitumor activity of novel pyrazoloquinoline derivatives
Bioorganic & Medicinal Chemistry Letters, 1995
Mammalian topoisomerase II inhibition activity has been identified in a series of novel pyrazoloquinoline derivatives; potency for two analogues containing cyclohexyl groups at the 2-position was comparable to the reference agents, mAMSA and VP-16. In several instances, topo II inhibition translated to a high level of in vitro cytotoxicity and murine antitumor activity. Introduction. We recently described the mammalian topoisomerase II inhibitory properties of quinolone
Simple C-2-Substituted Quinolines and their Anticancer Activity
Letters in Drug Design & Discovery, 2012
Sixteen C-2-substituted quinolines were tested in both human cancer cell lines and normal cell lines (Vero and THP-1). Preliminary results indicate that 2-!-furyl-and 2-"-pyridinyl quinoline derivatives 1, 13 and 14 are active against three human cancer cell lines and, at the same time, were devoid of cytotoxic effect on normal cells. Biological activity and SAR results were compared with different molecular descriptors determined in silico using online available software, in an attempt to show a relationship with the possible mode of action of these quinoline derivatives.