Synthesis and anti-cancer activity of chalcone linked imidazolones (original) (raw)
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Synthesis of Imidazothiazole-Chalcone Derivatives as Anticancer and Apoptosis Inducing Agents
ChemMedChem, 2010
A new class of imidazo[2,1-b]thiazole chalcone derivatives were synthesized and evaluated for their anticancer activity. These chalcone derivatives show promising activity, with log GI(50) values ranging from -7.51 to -4.00. The detailed biological aspects of these derivatives toward the MCF-7 cell line were studied. Interestingly, these chalcone derivatives induced G(0)/G(1)-phase cell-cycle arrest, down-regulation of G(1)-phase cell-cycle regulatory proteins such as cyclin D1 and cyclin E1, and up-regulation of CDK4. Moreover, these compounds elicit the characteristic features of apoptosis such as enhancement in the levels of p53, p21, and p27, suppression of NF-κB, and up-regulation of caspase-9. One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies.
ChemistrySelect, 2020
In this approach we applied a green synthetic protocol for the preparation of a novel series of imidazotriazole derivatives under solvent free conditions and shorter reaction times utilizing the reactive 2-thioxoimidazolidinone derivative 1 as a starting substrate. Different substituted imidazo[2,1-c][1,2,4] triazolone derivatives 2-4,6 and imidazo[1,2-b][1,2,4]triazolone derivatives 8-10, 12, 13, 15, 16 and 18 were synthesized. We carried out the synthesis of the open chain analogues phenylimidazolidin-2-ylidenepicolinohydrazide 5, dihydroimidazolylacetamide 11, imidazolylpicolinamide 14, pentahydroxyhexylideneaminoimidazol-5-one derivative 17, dihydroimidazolyl-N,N-dimethylformimidamide 19 and the dihydroimidazo[1,2-b] [1,2,4]triazepine-7-carbonitrile 20. The synthetic methods involved mainly fusion of compound 1 with the appropriate reagents. The in vitro anticancer evaluation at the National Cancer Institute (NCI), USA at a single dose (10 À 5 M) in full NCI 60 cell panel revealed that a significant inhibition for some cancer cells was observed with compounds 11 and 17-19 (38-67.5 % inhibition).These novel compounds displayed appreciable anticancer activities against different cancer cell lines including leukemia, colon cancer, melanoma, ovarian cancer, renal cancer and non-small cell lung cancer cell lines.
Chalcones and its derivatives have attracted increasing attention due to numerous pharmacological applications. They have displayed a broad spectrum of pharmacological activities. DMF/POCl 3 complex was used for intramolecular cyclization and cyclodehydration of imidazolinones (7a-e). A new series of six substituted imidazolone-chalcone derivatives (9a-f) have been synthesized by the condensation of imidazolones (7a-e) with various aldehydes (4a-e). The precursor was synthesized by the reaction of arylidene-2-phenyloxazolones (5a-e) with p-aminoacetophenone (6). Structures of the intermediate and final compounds were confirmed by IR, MS and NMR studies. In this present work, imidazolones linked chalcones were synthesized in presence of general reagents, at a faster rate in excellent yields. All the final compounds (9a-f) were screened for their anticancer and antioxidant activities by MTT assay on various cell lines and Nitric Oxide scavenging assay respectively. All the compounds have good to excellent activity.
Synthesis of chalcone-amidobenzothiazole conjugates as antimitotic and apoptotic inducing agents
Bioorganic & Medicinal Chemistry, 2012
A series of chalcone-amidobenzothiazole conjugates (9a-k and 10a,b) have been synthesized and evaluated for their anticancer activity. All these compounds exhibited potent activity and the IC 50 of two potential compounds (9a and 9f) against different cancer cell lines are in the range of 0.85-3.3 lM. Flow cytometric analysis revealed that these compounds induced cell cycle arrest at G2/M phase in A549 cell line leading to caspase-3 dependent apoptotic cell death. The tubulin polymerization assay (IC 50 of 9a is 3.5 lM and 9f is 5.2 lM) and immuofluorescence analysis showed that these compounds effectively inhibit microtubule assembly at both molecular and cellular levels in A549 cells. Further, Annexin staining also suggested that these compounds induced cell death by apoptosis. Moreover, docking experiments have shown that they interact and bind efficiently with tubulin protein. Overall, the current study demonstrates that the synthesis of chalcone-amidobenzothiazole conjugates as promising anticancer agents with potent G2/M arrest and apoptotic-inducing activities via targeting tubulin.
Medicinal Chemistry Research, 2020
An efficient, one-pot multicomponent reaction of novel pyrazolo-oxothiazolidine derivatives was achieved by condensation of 1-(benzofuran-2-yl)-3-(substituted-arylprop-2-en-1-ones, thiosemicarbazide and dialkyl acetylenedicarboxylates under the optimized reaction conditions. Synthesised compounds were evaluated for their antiproliferative activity against A549 human lung cancer cell line. Among all the tested compounds, 4a (IC 50-0.930 lg/mL), 4e (IC 50-1.207 lg/mL), 4f (IC 50-0.808 lg/ mL), 4g (IC 50-1.078 lg/mL), 4h (IC 50-0.967 lg/mL) and 4j (IC 50-2.445 lg/mL) showed promising activity compared with standard drug Sorafenib (IC 50-3.779 lg/mL). Molecular docking studies indicated that compound 4f had the greatest affinity for catalytic site of receptors EGFR (PDB ID code: 1 M17) and VEGFR2 (PDB ID code: 4AGD, 4ASD). These novel pyrazolo-oxothiazolidine derivatives can be promising therapeutic agents for A549 human lung cancer cell line.
A series of hybrid of triazoloquinoxaline-chalcone derivatives 7a-k were designed, synthesized, fully characterized, and evaluated for their cytotoxic activity against three target cell lines: human breast adenocarcinoma (MCF-7), human colon carcinoma (HCT-116), and human hepatocellular carcinoma (HEPG-2). The preliminary results showed that some of these chalcones like 7b-c, and 7e-g exhibited significant antiproliferative effects against most of the cell lines, with selective or non-selective behavior, indicated by IC 50 values in the 1.65 to 34.28 µM range. In order to investigate the mechanistic aspects of these active compounds, EGFR TK and tubulin inhibitory activities were measured as further biological assays. The EGFR TK assay results revealed that the derivatives 7a-c, 7e, and 7g could inhibit the EGFR TK in the submicromolar range (0.093 to 0.661 µM). Moreover, an antitubulin polymerization effect was noted for the active derivatives compared to the reference drug colchicine, with compounds 7e and 7g displaying 14.7 and 8.4 micromolar activity, respectively. Furthermore, a molecular docking study was carried out to explain the observed effects and the binding modes of these chalcones with the EGFR TK and tubulin targets.
Synthesis and anticancer evaluation of imidazolinone and benzoxazole derivatives
Arabian Journal of Chemistry, 2014
A series of imidazolinone and benzoxazole derivatives (3 and 5) have been synthesized by the condensation of oxazolinone derivatives (2a-c) with aniline and 2-hydroxyaniline. Acetyl derivatives (4, 6 and 7) were prepared via acetylation of compounds 3 and 5 with acetic anhydride and chloroacetyl chloride. The results revealed that imidazolinone and benzoxazole derivatives are potent against the cancer cell lines MCF-7 and HePG2. In particular, benzoxazole derivatives are more potent than imidazolinone derivatives.