Synthesis and Evaluation of New Series of 1,4-Dihydropyridine Derivatives as Anticancer Agents (original) (raw)
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Medicinal Chemistry, 2012
Two series of compounds with the general formula of 4,6-diaryl-2-oxo-1,2 dihydropyridine-3carbonitriles and their isosteric imino derivatives were synthesized through a one pot reaction of acetophenone, aldehyde and ammonium acetate with ethyl cyanoacetate or malononitrile, respectively. The synthesized compounds were evaluated for tumor cell growth inhibitory using the human HT-29 colon and MDA-MB-231 breast tumor cell lines. Compound 4-(2-Ethoxyphenyl)-2-imino-6-(4-fluorophenyl)-1,2-dihydropyridine-3 carbonitrile (6) showed IC 50 value of 0.70 μM versus HT-29. Meanwhile, compound 4-(2-Hydroxyphenyl)-2-imino-6-(4fluorophenyl)-1,2-dihydropyridine-3-carbonitrile (4) showed IC 50 value of 4.6 μM versus MDA-MB-231. Docking compound 10 to possible molecular targets, survivin and PIM1 kinase showed appreciable interactions with both, which suggest possible targets for the antitumor activity of this novel class of anticancer compounds.
Archiv der Pharmazie, 2010
A series of twenty new 4‐substituted‐2,6‐dimethyl‐3,5‐bis‐N‐(heteroaryl)‐carbamoyl‐1,4‐dihydropyridines have been prepared from a three‐component one‐pot condensation reaction of N‐heteroaryl acetoacetamide, an aromatic/heteroaromatic aldehyde, and ammonium acetate under four different experimental conditions. Except for the conventional method, all the experimental conditions were simple, eco‐friendly, economical, and the reactions were rapid and high‐yielding. The methods employed have been compared in terms of yields, cost, and simplicity. The synthesized compounds were characterized by different spectroscopic techniques and evaluated for their in‐vitro anticancer, antibacterial, and antitubercular activities. Amongst the compounds tested, compound 25 exhibited the highest anticancer activity while compounds 14 and 18 exhibited significant antibacterial and antitubercular activities.
Synthesis and Evaluation of Triazolyl Dihydropyrimidines as Potential Anticancer Agents
International Journal of Chemistry, 2018
Novel N – triazolyl 3(a-f) and O-triazolyl (4a-f) derivatives of 4, 6-diaryl-1, 4-dihydropyrimidines were synthesized through mannich reaction. All compounds were characterized by physical and spectral data. These compounds were screened for in vitro efficiency in human breast cancer cell (MCF-7&MDA-MB-231) lines and found to have very good anti-proliferative activity. Among all compounds of 4b, 3e, 4e endowed with lesser respective IC50 values of 31.94, 55.73, 55.03 µM in MCF-7 cells and 41.50, 35.28, 32.06 µM in MDA-MB 231 cells by MTT assay. In further studies, Compounds 4b, 3e, 4e were found to arrest cell growth at S phase in MCF-7 cells. In MDA-MB 231 cells, 4b, 4e were found to arrest the cells in S phase, and compound 3e found to arrest G2/M phase when compared to the standard drug tamoxifen, arrested S phase in MCF-7 cells and G0/G1 phase in MDA-MB 231 cells.
A number of 1,4-dihydropyridine derivatives (9a-d, 10a-d and 11a-d) were designed and synthesized by the reaction of 1,3,4-oxadiazole-5-thiones and 1,2,4-triazole-5-thiones to 2,6-dibromomethyl-3,5-diethoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine. The synthesized compounds were characterized using FT-IR, 1 H-NMR, 13 C-NMR spectral data, ESI-MS and elemental analysis. The cytotoxicity of the synthesized compounds was evaluated in human breast cancer (MCF-7) cells based on the results of MTT assay. The results indicated that compound diethyl 4-(3-nitrophenyl)-2,6-bis[((5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl)thio)methyl]-1,4-dihydro pyridine-3,5-dicarboxylate (9b) with (IC 50 = 23±2.32 µM) was the most potent derivative against MCF-7 cells. Based on the results, the use of oxadiazole moiety in the C2 and C6 positions of 1,4-dihydropyridine ring system enhanced the cytotoxic potential of these derivatives. Therefore, some of the oxadiazole-substituted 1,4-DHPs may facilitate further modifications which result in the discovery of potent cytotoxic agents.
Madridge J Pharm Res, 2019
Background and Objective: Inflammation is believed to incite carcinogenesis by causing cell and genome damage. Tetrahydropyridines have gained significant synthetic interest because they constitute biologically active features of pharmaceutical agents. Previous tetrahydropyridines developed by our research group were effective in inhibiting inflammation. Since there is a relationship between inflammation and cancer, the objective of this manuscript is to expand our prior study to determine the anti-cancer activity of novel tetrahydropyridine analogs. Materials and methods: 3-Ethylpyridine reacted with O-mesitylenesulfonylhydroxylamine to furnish N-amino-3-ethylpyridinium mesitylenesulfonate. The reaction of N-amino-3-ethylpyridinium mesitylenesulfonate with substituted acid chlorides gives the stable crystalline pyridinium ylides. A sodium borohydride reduction of ylides furnishes the target compounds, N-substituted [benzoylamino]-5-ethyl-1,2,3,6-tetrahydropyridines. The evaluation of these analogs cytotoxicity against Ishikawa, MCF-7, and MDA-MB-231 cell lines were determined after 72 hours of drug exposure employing CellTiter-Glo assay. To explore the interaction between the tetrahydropyridine derivatives and estrogen receptor alpha, SYBYL-X 2.1 was used to determine the best bioactive conformations of the tetrahydropyridine derivatives for the active site of the receptor. Results: Four novel N-substituted [benzoylamino]-5-ethyl-1,2,3,6-tetrahydropyridines were synthesized, purified, and characterized. The four tetrahydropyridine analogs exhibited some anti-cancer activity. Based on the molecular modeling studies, EH3 was expected to have the best antiproliferative activity due to having the highest docking score for ERα. However, EH2 had the best antiproliferative activity. Nevertheless, the biological screening and molecular modeling can provide insight to help with the design of more biologically active compounds as potential anti-cancer agents.
Two series of novel substituted 1,4-dihydropyridine derivatives incorporating nitrogen mustard pharmacophore hybrids without spacer DHP-M (4a–4d) and with ethyl spacer DHP-L-M (8a–8g) were designed and synthesized. They were subjected to in silico ADME prediction study to check their drug-like properties and evaluated for their cytotoxicity against: A 549 (lung), COLO 205 (colon), U 87 (glioblastoma), and IMR-32 (neuroblastoma) human cancer cell lines in vitro using 3-(4,5- dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay against chlorambucil and docetaxel. Majority of the test compounds exhibited moderate to significant cytotoxic activity. The highest activity in all the investigated cancer cells was displayed by DHP-M (4a). This may be due to the less steric hindrance offered by 4a.
Central European Journal of Chemistry, 2010
A series of N-(6-methylbenzothiazolyl)-2,3,5,6-tetrasubstituted-4-(aryl)-1,4-dihydropyridines were synthesized by reaction of 2-amino-6-methylbenzothiazole, aromatic aldehyde and active methylene compound in methanol by conventional, as well as, microwave irradiation (solvent free and solid support) methods. The microwave irradiation technique gives better yield and shorter reaction time. Among solid supported microwave irradiation better yields are obtained in acidic alumina as compared to silica, neutral alumina, and basic alumina. All compounds were tested for antibacterial and antifungal activities and results have been compared with standard drugs. Entomological activities were also tested. The results showed that a change in the substitution pattern in 1,4-dihydropyridine derivatives may cause a marked effect on their antimicrobial activity.
2018
CDK2, which plays a vital role as a regulator of cell growth, is one of the intensely studied TK targets of anticancer inhibitors. The present investigation dealt with design (docking and binding energy), which used to select the promising proposed compounds for the synthesis of novel, diverse 14 pyrido[2,3-d]pyrimidine derivatives as potential anticancer agents targeting CDK2. All the newly synthesized compounds were screened for their anticancer activity against MCF-7 and CaCO2 and 14 compounds were found to be active. Compounds 6c and 8d showed significant activity with IC50 values 7.4 and 5.5 on MCF-7 respectively. Most of the synthesized compounds were subjected to enzyme assay (CDK2 TK) for measuring their inhibitory activity. The preliminary results revealed that compound 8d, which proves potent inhibitory activity toward tumor growth and potent activity on the CDK2 TK enzyme with 89% inhibition compared to ATP would be a potential anticancer agent.
Synthesis, Charecterisation and biological Evaluation of Novel Hantzsch 1,4-dihydropyridines
We report a library consisting of some novel Hantzsch dihydropyridines of biological interest as well as their synthesis and analysis. The important steps in the synthetic part were found to be Hantzsch reactions. The synthesized compounds were screened for their in vitro antibacterial activity against two gram-positive bacteria: Staphylococcus aureus and Bacillus subtilis. The title compounds did not exhibit potential antibacterial activity. Furthermore, compounds were subjected to in vitro cytotoxicity against Vero cells. Compounds exhibited weak, moderate, or high cytotoxicity. Compounds 9b, 9c, 9d, 9e, 9f, 9g exhibited potential cytotoxicity.
European Journal of Chemistry, 2013
A novel series of tricyano substituted polyfunctional 5,6-dihydropyridine 8a-n bearing functionalized aromatic rings at C-4 and C-6 position have been prepared from (αmethylbenzylidene) malononitriles in good to excellent yields (52-98%) in solvent free conditions. All the synthesized compounds (8a-n) were evaluated for their in vitro urease inhibition and anticancer activity against prostate cancer (PC3) and Hela cell lines. Compound 8k (4,6-bis(4-methoxyphenyl)-5,6-dihydropyridin) showed slightly better urease inhibitory potential (IC50 = 20.47 µM) as compared to standard thiourea (IC50 = 21 µM). Whilst in the case of anticancer studies the compound 8a 2-(4,6-bis(4-bromophenyl)-6-methyl-5,6dihydropyridin found to be most active (IC50 = 4.40 and 8.80 µM) among the series when compared with standard doxorubicin 4 (IC50 = 0.91 and 3.