Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure–activity relationships of the 7- and 5-, 6-, 8-positions

Kemnitzer, William; Kasibhatla, Shailaja; Jiang, Songchun; Zhang, Hong; Zhao, Jianghong; Jia, Shaojuan; Xu, Lifen; Crogan-Grundy, Candace; Denis, Real; Barriault, Nancy; Vaillancourt, Louis; Charron, Sylvie; Dodd, Jennifer A.; Attardo, Giorgio; Labrecque, Denis; Lamothe, Serge; Gourdeau, Henriette; Tseng, Ben; Drewe, John; Cai, Sui Xiong

doi:10.1016/j.bmcl.2005.07.066

Cited by 234 publications

(119 citation statements)

References 17 publications

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“…Searching the literature revealed the outstanding activity of 4-aryl-4H-chromenes as apoptotic inducers and cytotoxic agents. Thus, 4-aryl-4H-chromenes (like compounds IV and V) were reported as potent apoptosis inducer in human breast cancer cells T47D [18][19][20] . Their SAR study indicated that both the 2-amino and the 3-cyano groups were essential for the antitumor activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives

Zaher

Abuel‐Maaty

El‐Nassan

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Three series of benzothiophene derivatives were designed and synthesized as cytotoxic agents. The compounds were subjected to in vitro antitumor screening at the National Cancer Institute (NCI), Bethesda, MD. The results of the single dose screening indicated that only the benzothieno[3,2-b]pyran series 3a-f exhibited potent and broad spectrum cytotoxic activity and was subjected to five dose cytotoxic screening. The most active compound in this study was 2-amino-6-bromo-4-(4-nitrophenyl)-4H-[1]benzothieno[3,2-b]pyran-3-carbonitrile (3e) with MG-MID GI 50 , TGI, and LC 50 values of 0.11, 7.94 and 42.66 mM, respectively. Compound 3e exhibited broad spectrum anticancer activity against a panel of 59 cell lines. To elucidate the underlying mechanism of compound 3e cytotoxic activity, we examined its effect on cell cycle progression and its ability to induce apoptosis using human colon adenocarcinoma cell line (HCT-116). The effect of compound 3e on the cell cycle progression indicated that exposure of HCT-116 cells to compound 3e for 24 and 48 h, induced a significant disruption in the cell cycle profile including time dependent decrease in cell population at G1 phase with concomitant increase in pre-G and G2/M cell population. Moreover, compound 3e induced time dependent increase in the percentage of early and late apoptotic and necrotic cell population. In conclusion, we were able to successfully design a new series of benzothieno [3,2-b]pyran derivatives with potent cytotoxic activity and their mechanism of cytotoxicity was examined.

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Section: Introductionmentioning

confidence: 99%

Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives

Zaher

Abuel‐Maaty

El‐Nassan

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…According to previous studies, other derivatives of these compounds would induce apoptosis in tumor cells by interaction of tubulin formation or inhibition in tubulin polymerization. The T47D cell line containing mutated P53 was used since the chromene derivatives have especially better effect on it [10,11,13].…”

Section: Discussionmentioning

confidence: 99%

“…Right balance between apoptosis and inhibition of apoptosis plays an important role in maintaining the homeostasis of tissue and organ morphogenesis [10,12]. Cytological and biochemical changes happen in certain cells during apoptosis, including condensation of nucleoplasm and cytoplasm, DNA fragmentation, and formation of apoptotic bounded membrane bodies that are identified and eliminated by adjacent cells [13,14]. Any fault in this process causes pathologic conditions such as deviations from apoptosis, which causes the tumor separation, metastasis and inducing apoptosis which leads to neurological diseases such as Alzheimer's [15,16].…”

mentioning

confidence: 99%

Cytotoxicity and Apoptosis Inducing Activities of 2-Amino-4H-chromene-3-carbonitrile Derivatives Loaded on Gold Nanoparticles Against Human Breast Cancer Cell Line T47D

et al. 2014

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Chemotherapy drugs, used for prevention of uncontrolled cell proliferation in certain tissues as well as inducing apoptosis in tumor cells, are important candidates for treatment of cancer. The synthesized 2-amino-4H-chromene-3-carbonitrile derivatives effective on cancerous cells resistant to other drugs such as Paclitaxel were used due to their ability in induction of apoptosis. The growth inhibitory and inducing apoptosis activities were determined. In order to make it target-oriented, the best compound was conjugated with gold nanoparticles (NPs) by aspartic acid with chemical reduction method. Cytotoxicity effect of 2-amino-4H-chromene-3-carbonitrile derivatives against the T47D breast cancer cell line was determined by MTT assay. The synthesis of gold NPs was confirmed by transmission electron microscopy, UV-Vis and dynamic light scattering. To assess the effects of compounds on the process of apoptosis, staining methods with acridine orange-ethidium bromide and Hoechst staining by fluorescence microscopy and DNA fragmentation by the diphenylamine method were used. The synthesized compounds containing two NH 2 groups on benzene rings, demonstrated more cytotoxicity effect. The effect of conjugation with gold NPs and the induction of apoptosis were studied with the best compound. The cytotoxicity effects of the synthesized 2-amino-4H-chromene-3-carbonitrile compounds were changed by replacement of NO 2 group on thiol ring with different chemical groups on the benzene ring. Analyses of treated cell lines by conjugated and non-conjugated forms of compounds verified their ability in inducing apoptosis while conjugated form demonstrated higher apoptosis.

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“…6-8. Some among them are extremely effective against such kind of diseases which influenced by nitrogen-activated protein kinase enzyme inhibitors. Some of them have antimicrobial activity , 11 cytotoxic effect against human cancer cells, 12 antiallergic activity, 13 central nervous system influencing activity, 14 antiproliferation activty. 15 Several derivatives are also widely used as agrochemicals, 16 antioxidant 17 and antiinflammatory agent.…”

Section: Introductionmentioning

confidence: 99%

An Expeditious and Green Approach for the Synthesis of 2-Amino-4h-Chromenes Using a Catalyst of Natural Origin

Bhosale¹,

Shisodia²,

Ingle³

et al. 2018

ECB

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A highly efficient three-component one step system for the synthesis of 2-amino-4H-chromens is developed. Excellent yields were obtained simply by mixing malononitrile, aromatic aldehyde and α-napthol in lemon juice as a catalyst of natural origin and solvent, avoiding using hazardous organic solvents. The main advantages of this method are its green method character, short reaction time and simple workup procedures and the lack of using any metal containing catalysts. * Corresponding Authors

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Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 2. Structure–activity relationships of the 7- and 5-, 6-, 8-positions

Cited by 234 publications

References 17 publications

Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives

Synthesis, antitumor screening and cell cycle analysis of novel benzothieno[3,2-b]pyran derivatives

Cytotoxicity and Apoptosis Inducing Activities of 2-Amino-4H-chromene-3-carbonitrile Derivatives Loaded on Gold Nanoparticles Against Human Breast Cancer Cell Line T47D

An Expeditious and Green Approach for the Synthesis of 2-Amino-4h-Chromenes Using a Catalyst of Natural Origin

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