Synthesis and anticancer evaluation of imidazolinone and benzoxazole derivatives (original) (raw)
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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.
Acta Pharmaceutica, 2000
2 The present work deals with the synthesis of some novel heterocyclic compounds such as benzoxazoles , 7, 13 and 19, imidazoles 3, 8, 14 and 20, benzimidazoles 4, 9, 15 and 21, and tetrazoles 10, 16, and 22. The synthesized compounds were characterized by IR, 1H NMR, mass spectrometry and elemental analysis. The compounds were evaluated for cytotoxicity against human cancer cell lines such as MCF-7 (breast cancer) and HT-29 (colon cancer) by the MTT assay method. Among the tested compounds, 4,4’-sulfonylbis(N-(2-(1H-benzo[d]imidazol- -2-yl)ethyl)aniline (9), N-bis(2-(benzo[d]oxazol-2-yl)-ethyl)- 6-phenyl-1,3,5-triazine-2,4-diamine (13), N-bis(2-(1H-benzo[ d]imidazol-2-yl)ethyl)-6-phenyl-1,3,5-triazine-2,4-diamine (15) and N-tris(2-1H-benzo[d]imidazol-2-yl)ethyl)- 1,3,5-triazine-2,4,6-triamine (21) showed potent cytotoxicity.
ACTA Pharmaceutica Sciencia, 2017
Cancer is the second leading cause of death after heart disease throughout the world. A great amount of anticancer drugs are discovered and still have been designed nowadays for cancer treatment 1. Today, treatments involving cytotoxic drugs are used in a widespread manner because of increasing in cancer incidence 2. Compounds containing imidazole and benzothiazole moiety have shown a wide range of biological properties including anticancer, antiviral, antitubercular, antimicrobial, antidiabetic, anti-inflammatory activities. These broad thera-ABSTRACT In this work, some novel N-(6-substituted-benzothiazol-2-yl)-2-[[4,5-dimethyl-1-((p-tolyl/4-nitrophenyl)amino)-1H-imidazol-2-yl]thio]acetamide derivatives were synthesized and searched for their cytotoxic activities against C6 and HepG2 tumor cells. Among all compounds, the most active compound was determined as compound 7. It was calculated IC 50 value about 15.67 µg/mL through C6 tumor cell lines and also compound 2, 4, 5, 6 were observed as good cytotoxic agents against HepG2 tumor cells. Findings about antiproliferative activity studies have encouraged the acquirement of new similar compounds in undergoing studies.
European Journal of Medicinal Chemistry, 2011
Thirteen novel benzazole derivatives were synthesized as possible anticancer agents. The first intermediate 1,3-benzothiazol-2-ylacetonitrile (2) was synthesized via cyclodeamination reaction of o-aminothiophenol (1) with malononitrile. Also, the second intermediate 5,6-dimethyl-1H-benzimidazol-2-ylacetonitrile (10) was afforded via cyclocondensation reaction between 4,5-dimethyl-1,2-phenylenediamine (9) and ethylcyanoacetate. Nucleophilic reaction of benzimidazolyl NH of compound (10) with ethylcyanoacetate afforded benzimidazolyl-3-oxopropanenitrile (11). On the other hand, methylenation of CH2 function of compound (10) with dimethylformamide/dimethylacetal afforded benzimidazolylprop-2-enenitrile 12. The synthesis of benzothiazoylpyridines 5a,b and 8a,b as well as benzimidazolylpyridines, 14a,b and 17a–d was carried out through Michael addition of compounds 2 or 10 with arylidenemalononitriles 3a,b and 4a–d. The combination of pharmacophoric anticancer moieties, pyridine and benzazoles was the base on which target compounds 5a,b, 8a,b, 14a,b and 17a–d were designed. Among the synthesized compounds, four derivatives 10 and 17b–d were selected by National Cancer Institute (NCI), USA to be screened for their anticancer activity at a single high dose (10−5 M) against a panel of 60 cancer cell lines. Compound 17b 4-[p-chlorophenyl]pyridine and 17d 4-[p- methoxyphenyl] pyridine exhibited a broad and moderate antitumor activity against 41 tumor cell lines belonging to the nine subpanels employed and are selected for further evaluation at five dose level screening.This article summarizes Micheal addition of benzazolyl-2-acetonitriles 2 and 10 with some arylidenemalononitriles, dicussing the different possible products of the reaction. Benzazolylpyridines 5a,b, 8a,b, 14a,b and 17a–d are confirmed as final products with excluding the reported fused pyridobenzazoles. Also, it handles the nucleophilic attack of different functional groups of 10 with ethylcyanoacetate and DMFDMA producing compounds 11 and 12 respectively. Four compounds selected for one dose assay as anticancer agents, two of them e.g. 17b and 17d passed to five dose assay. TGI, LG50, LC50 were recorded and comparatively studied for the tested cancer cell lines. ► Benzazoles 2 or 10 reacted with arylidenemalononitriles to afford benzazolylpyridines. ► Nucleophilic reaction of 10 with ethylcyanoacetate afforded oxopropanenitrile 11. ► Methylenation of 10 with DMFDMA afforded Benzimidazolylprop-enenitrile 12. ► Compounds 17b, 17d are selected by NCI to five dose assay as anticancer agents.
Bioorganic & Medicinal Chemistry Letters, 2012
Two new series of benzimidazole bearing oxadiazole[1-(1H-benzo[d]imidazol-2-yl)-3-(5-substituted-1,3,4-oxadiazol-2-yl)propan-1-ones (4a-l)] and triazolo-thiadiazoles[1-(1H-benzo[d]imidazol-2-yl)-3-(6-(substituted)-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazol-3-yl)propan-1-one (7a-e)] have been synthesized successfully from4-(1H-benzo[d]imidazol-2-yl)-4-oxobutanehydrazide (3) with an aim to produce promising anticancer agents. In vitro anticancer activities of synthesized compounds were screened at the National Cancer Institute (NCI), USA, according to their applied protocol against full NCI 60 human cell lines panel; results showed good to remarkable anticancer activity. Among them, compound (4j, NCS: 761980) exhibited significant growth inhibition and further screened at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 lM) with GI 50 values ranging from 0.49 to 48.0 lM and found superior for the non-small cell lung cancer cell lines like HOP-92 (GI 50 0.49, TGI 19.9,LC 50 >100 and Log 10 GI 50 À6.30, Log 10 TGI À4.70, Log 10 LC 50 >À4.00).
Turkish Journal of Chemistry, 2004
A series of novel 3-alkyl-4-cyclohexylmethylenamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (6a-e) and 3alkyl-4-hexylidenamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (7b-e) were synthesized from the reaction of corresponding 3-alkyl-4-amino-5-oxo-4,5-dihydro-[1,2,4]triazoles (1) with cyclohexancarboxaldehyde and capronaldehyde. The acetylation of compounds 6e and 7b resulted in the formation of 1-acetyl-4cyclohexylmethylenamino-5-oxo-3-(p-tolyl)-4,5-dihydro-[1,2,4]triazole (10) and 3-benzyl-4-hexylidenamino-5-oxo-4,5-dihydro-[1,2,4]triazole (11). 3-Alkyl-4-cyclohexylmethylamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (8a-e) and 3-alkyl-4-hexylamino-5-oxo-4,5-dihydro-[1,2,4]triazoles (9b-e) were obtained from the selective reduction of compounds 6a-e and 7b-e with NaBH4. The in vitro antitumor activity of some selected compounds was screened by the National Cancer Institute (USA) against several human tumor cell lines, and compounds 8c, 9d and 11c were found to be active.
European Journal of Medicinal Chemistry, 2010
In the present study 18 novel imidazole-(benz)azole and imidazoleepiperazine derivatives were synthesized in order to investigate their probable anticancer activity. The structures of the compounds were confirmed by IR, 1 H NMR and EI-MS spectral data. Cytotoxicity (MTT), analysis of DNA synthesis and detection of apoptotic DNA assays were applied to determine anticancer activity of the compounds against colon (HT-29) and breast (MCF-7) carcinoma cell lines. Most of the compounds, showed greater activity against HT-29 cells than MCF-7 cells. Some of them indicated considerable cytotoxicity against both of the carcinogenic cell lines. However, their inhibitory activity on DNA synthesis was relatively poor. Anticancer activity screening results revealed that 11, 12 and 13 were the most active compounds in the series. They exhibited significant cytotoxicity against both of the carcinogenic cell lines and caused DNA fragmentation of the HT-29 cells.
Molecules
The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylide...