Structure Based Drug Discovery, Docking, Modelling, Synthesis and Anticancer Screening of Some Novel Quinoline Derivatives (original) (raw)
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MOLECULAR DOCKING AND ADMET STUDY OF QUINOLINE-BASED DERIVATIVES FOR ANTI-CANCER ACTIVITY
An In silico study was carried out on a series of novel quinoline based inhibitors which were designed, synthesized and assessed for their in vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA-MB231 by Arafa RK et. al. We have designed these 22 inhibitors in ChemBioOffice 2010 and minimized using the LigPrep tool of Schrödinger 2011. Docking study of these inhibitors was performed on different cancer proteins in order to give a suggestion to the proposed in vitro mechanism of action. Some prominent cancer proteins specifically causing breast and colon cancers are used as targets in this computational study to predict the most active quinoline based derivative. The proteins are minimized using the protein preparation wizard and Grid is generated by specifying the active site amino acids. The binding model of best scoring inhibitor with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. Interestingly the result of docking was found to match with the previous invitro study where the most active derivative against both tested cell lines was the Schiff's base 4e. The pharmacokinetic parameters study was done using the QikProp 3.4 tool to display ADME and toxicity properties of these inhibitors.
Anti-Cancer Activity and Molecular Docking of Some Pyrano[3,2‑c]quinoline Analogues
Open Journal of Medicinal Chemistry, 2020
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.
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.
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 and Molecular Docking Study of Novel Pyrazolo[3,4-b]quinoline Derivatives 1a-d 4a-e, 9
Phenylpyrazolo[3,4-b]quinolin-3-ols were prepared by using 2-chloroquinoline-3-carboxylic acids and phenyl hydrazine hydrochlorides in the presence of POCl 3. One of the phenylpyrazolo[3,4-b]quinolin-3-ols underwent chlorination (9). To check binding modes and binding affinity of synthesized compounds were docked with the active sites of human telomerase (hTERT). The results indicated that compound 4b has good affinity to the active site residue of human telomerase, least energy (-23.012 score).
European Journal of Medicinal Chemistry, 2010
Novel derivatives of quinazoline (1e27) have been synthesized and tested for their antitumor activity against three tumor cell lines among these cell lines the human breast carcinoma cell line (MCF-7) in which EGFR is highly expressed. All tested compounds showed potent and selective activity against breast cancer (MCF-7) with IC 50 range of 3.35e6.81 mg/ml. With regarding broad-spectrum activity compounds 5, 9, 15, 18 and 20 exploited potent antitumor against human liver cell line (HEPG2), human breast cell line (MCF-7) and human cervix cell line (HELA) with IC 50 range of 3.35e5.59 mg/ml. Virtual screening was carried out through docking the designed compounds into the ATP binding site of epidermal growth factor receptor (EGFR) to predict if these compounds have analogous binding mode to the EGFR inhibitors.
Pyrazolo[3,4- d]pyrimidine derivatives were synthesized from 4-hydrazino-7-methoxy quinoline(2)with thoxymethylenecyanoacetate afforded ethyl 5-amino-1-(7- methoxyquinolin-4-yl)-1H-pyrazole-4-carboxylate(3). The compound (3) washydrolysed to get 5-amino-1-(7- methoxyquinolin-4-yl)-1H-pyrazole-4-carboxylic acid (4) and then reacted with acetic anhydride to afford 1-(7- methoxyquinolin-4-yl)-6-methylpyrazolo[3,4-d][1,3]oxazin- 4(1H)-one(5), which was condensed with different aromatic amines to give a series of 5-substituted 1-(7-methoxyquinolin-4-yl)-6-methyl-5-aryl-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one(6). The newly synthesized title compounds were characterized and evaluatedfor their antibacterial, antioxidant activity and molecular docking studies.
Synthesis, Characterization and Molecular Docking of Novel Quinoline and Pyridine Derivatives
Oriental journal of chemistry, 2017
A new series of substituted quinoline and pyridine derivatives 6a-h are synthesized by the coupling of hydrazide derivatives 4a-b with substituted carboxylic acids 5a-c in the presence of N,N,N',N'-tetramethyl-o-(benzotriazol-1-yl) uranium tetrafluoroborate TBTU as a coupling agent and lutidine as a base. The newly synthesized compounds 6a-l is characterized by analytical NMR and mass spectral data. The newly synthesized compounds were subjected to molecular docking studies for the inhibition of human Aurora A kinase target to evaluate their potential value for the treatment of cancers.
IOSR Journals , 2019
New classes of quinoline derivatives 2a, b, 7a, b, diazepine derivatives 3a, b, 8a, b, pyrimidine derivatives 4a, b, 5a, b; 6 had been synthesized, via reactions between visnagine carbaldehyde 1 and different reagents. The structures of the products were elucidated by spectra and elemental analyses. In the present work, the derivative products have been tested, along with reference compounds, for their cytotoxic potential against two tumor cell lines. The anticancer activity results indicated that the products 3b, 5b and 7b showed growth inhibition activity against HEPG2 cell line and products 4b, 6, and 8a showed growth inhibition activity against MCF-7. Moreover, we attempted an in-silico approach to gain insights into their binding modes against cyclin-dependent protein kinase 2 (CDK-2) which is involved in cell cycle, and receptor protein B-cell lymphoma 2 (BCL-2) which is involved in cell apoptosis. These targets were selected based on their key roles in cancer progression via the regulation of the cell cycle and DNA replication. Molecular-docking analyses revealed that compound 4b was the best docked ligand against both targets, as it displayed the lowest binding energy, and critical hydrogen bonds and hydrophobic interactions with the targets.
Archiv der Pharmazie, 2011
To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.