Novel coumarin-3-(N-aryl)carboxamides arrest breast cancer cell growth by inhibiting ErbB-2 and ERK1

Reddy, N. Srinivasa; Gumireddy, Kiranmai; Mallireddigari, Muralidhar R.; Cosenza, Stephen C.; Padmavathi, V.; Bell, Stanley C.; Reddy, E. Premkumar; Reddy, M. V. Ramana

doi:10.1016/j.bmc.2005.02.051

Cited by 58 publications

(31 citation statements)

References 20 publications

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“…The corresponding coumarin-3-carboxamides were found to arrest breast cancer cell growth by inhibiting Er6B-2 phosphorylation. No significant cytotoxicity against normal human fibroplasts has been observed, implicating a high degree of tumor specificity for these compounds [111]. The representative active compound is the dichloro aryl amide 83.…”

Section: Anti-cancer Activitymentioning

confidence: 99%

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Kulkarni¹,

Kulkarni²,

Chao³

et al. 2006

CMC

221

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Coumarins, also referred as benzopyran-2-ones, and their corresponding nitrogen counterpart, 1-azacoumarins also referred to as carbostyrils, are a family of nature-occurring lactones and lactams respectively. The plant extracts containing coumarin-related heterocycles, which were employed as herbal remedies in early days, have now been extensively studied for their biological activities. These investigations have revealed their potentials as versatile biodynamic agents. For example, coumarins with phenolic hydroxyl groups have the ability to scavenge reactive oxygen species and thus prevent the formation of 5-HETE and HHT in the arachidonic pathway of inflammation suppression. Recent in vivo studies have revealed the role of coumarins in hepatotoxicity and also in depletion of cytochrome P450. Similarly 1-azacoumarins which is part of quinoline alkaloids, are known for their diverse biological activity and recently, a 6-functionalized 1-aza coumarins are undergoing human clinical trials as an orally active anti-tumor drug in view of its farnesyl protein-inhibiting activity in the nanomolar range. Furthermore, several synthetic coumarins with a variety of pharmacophoric groups at C-3, C-4 and C-7 positions have been intensively screened for anti-microbial, anti-HIV, anti-cancer, lipid-lowering, anti-oxidant, and anti-coagulation activities. Specifically, coumarin-3-sulfonamides and carboxamides were reported to exhibit selective cytotoxicity against mammalian cancer cell lines. The C4-substituted aryloxymethyl, arylaminomethyl, and dichloroacetamidomethyl coumarins, along with the corresponding 1-azacoumarins, have been demonstrated to be potential anti-microbial and anti-inflammatory agents. To expand the structural diversity of synthetic courmarins for biological functions, attempts have also been made to attach a chloramphenicol side chain at C-3 position of courmarin. In addition, the bi- and tri-heterocyclic coumarins and 1-azacoumarins with benzofuran, furan and thiazole ring systems along with biocompatible fragments like vanillin have shown remarkable potency as anti-inflammatory agents in animal models. Photobiological studies on pyridine-fused polycyclic coumarins have highlighted their potential as thymine dimer photosensitisers and the structurally related compounds of both coumarin and carbostyrils have also been found to act via the DNA gyrase pathway in their anti-bacterial activity. Apart from the above works, the present review also addresses the potential roles of coumarins and carbostyrils as protease inhibitors, or fluorescent probes in mechanistic investigation of biochemical pathways, and their application for QSAR in theoretical studies. Though 1-Azacoumarins have received less attention as compared to coumarins in the literature, an attempt has been made to compare both the systems at various stages, so that it can spark new thoughts on synthetic methodologies, reactivity pattern and biological activities.

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Section: Anti-cancer Activitymentioning

confidence: 99%

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Kulkarni¹,

Kulkarni²,

Chao³

et al. 2006

CMC

221

View full text Add to dashboard Cite

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“…Another recent work showed that coumarin-3-carboxamides (7, Fig. 1) tightly related to the chemical structure of 1 and 2 selectively inhibited the tumour cells that have a high level of epidermal growth factor receptor (EGRF or erbB1) and erbB2 (HER2) receptor expression [16].…”

Section: Introductionmentioning

confidence: 95%

6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

Kempen

Hemmer

Counerotte

et al. 2008

European Journal of Medicinal Chemistry

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Novel 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives were synthesized and their potency in reducing the invasive behaviour of HT 1080 fibrosarcoma cells was evaluated. Structure-activity relationships were deduced from biological results and will be used in further design of new active compounds. In particular, the acetoxymethyl substituent found at the 6-position of previously described active compounds can be replaced by an acetamidomethyl substituent without loss of potency; while the presence of an aryl ester function at the 3-position was preferred to a thioester or an amide function to induce marked biological activity.This work confirms the interest of aryl esters of 6-substituted coumarin-3-carboxylic acids as potential new anticancer agents.

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“…For all samples 0.00154% AcONH 4 was added to water. The active methylene compounds 10 , 49 13 , 50 and 16 (51) and amino compounds ( 21 and 22 ) 30 were prepared as per the reported procedures.…”

Section: Experimental Sectionmentioning

confidence: 99%

Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

et al. 2014

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The success of imatinib, a BCR-ABL inhibitor for the treatment of chronic myelogenous leukemia, has created a great impetus for the development of additional kinase inhibitors as therapeutic agents. However, the complexity of cancer has led to recent interest in polypharmacological approaches for developing multi kinase inhibitors with low toxicity profiles. With this goal in mind, we analyzed more than 150 novel cyano pyridopyrimidine compounds and identified structure activity relationship trends that can be exploited in the design of potent kinase inhibitors. One compound, 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) was found to be the most active, inducing apoptosis of tumor cells at a concentration of approximately 30–100nM. In vitro kinase profiling revealed that 7x is a multi-kinase inhibitor with potent inhibitory activity against the CDK4/CYCLIN D1 and ARK5 kinases. Here, we report the synthesis, structure activity relationship, kinase inhibitory profile, in vitro cytotoxicity and in vivo tumor regression studies by this lead compound.

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Novel coumarin-3-(N-aryl)carboxamides arrest breast cancer cell growth by inhibiting ErbB-2 and ERK1

Cited by 58 publications

References 20 publications

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

Recent Advances in Coumarins and 1-Azacoumarins as Versatile Biodynamic Agents

6-Substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid derivatives in a new approach of the treatment of cancer cell invasion and metastasis

Discovery of 8-Cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a Potent Inhibitor of Cyclin-Dependent Kinase 4 (CDK4) and AMPK-Related Kinase 5 (ARK5)

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