- Discovery of 4H-chromeno[2,3-d]pyrimidin-4-one derivatives as senescence inducers and their senescence-associated antiproliferative activities on cancer cells using advanced phenotypic assay
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Current research suggests therapy-induced senescence (TIS) of cancer cells characterized by distinct morphological and biochemical phenotypic changes represent a novel functional target that may enhance the effectiveness of cancer therapy. In order to identify novel small-molecule inducers of cellular senescence and determine the potential to be used for the treatment of melanoma, a new method of high-throughput screening (HTS) and high-contents screening (HCS) based on the detection of morphological changes was designed. This image-based and whole cell-based technology was applied to screen and select a novel class of antiproliferative agents on cancer cells, 4H-chromeno[2,3-d]pyrimidin-4-one derivatives, which induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. To evaluate structure-activity relationship (SAR) study of 4H-chromeno[2,3-d]pyrimidin-4-one scaffold starting from hit 3, a focused library containing diversely modified analogues was constructed and which led to the identification of 38, a novel compound to have remarkable anti-melanoma activity in vitro with good metabolic stability.
- Oh, Sangmi,Lee, Ji Young,Choi, Inhee,Ogier, Arnaud,Kwon, Do Yoon,Jeong, Hangyeol,Son, Sook Jin,Kim, Youngmi,Kwon, Haejin,Park, Seijin,Kang, Hwankyu,Kong, Kwanghan,Ahn, Sujin,Nehrbass, Ulf,Kim, Myung Jin,Song, Rita
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- Reaction of 2-imino-2H-chromene-3-carboxamide with some phosphorus esters: Synthesis of some novel chromenes containing phosphorus heterocycles and phosphonate groups and their antioxidant and cytotoxicity properties
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Novel chromenyl α-aminophosphonic acid 4 and dialkyl chromenyl phosphonate 6 have been obtained. In addition, some novel types of chromene fused with phosphorus heterocycles such as chromeno[4,3-c][1,2]azaphospholes 5 and 7, chromeno[2,3-d][1,3,2]diazaphosphinine 8 and 1,2-oxaphosphinino[3,4-c]pyridine 10 have been synthesized. The methodology depended on treatment of 2-imino-2H-chromene-3-carboxamide (1) with some phosphorus esters. The synthesized compounds were evaluated for antioxidant and cytotoxic activities. Among the synthesized compounds, compound 5 exhibited the most antioxidant activity with IC50 = 2.8 μg/mL in comparison with ascorbic acid as standard antioxidant. Also, compound 5 had significant cytotoxic effects against four cancer cell lines. Its IC50 values ranged between 4.96 and 7.44 μg/mL in comparison to doxorubicin (IC50 = 0.426–0.493 μg/mL).
- Ali, Tarik E.,Assiri, Mohammed A.,El-Shaaer, Hafez M.,Hassan, Mohamed M.,Fouda, Ahmed M.,Hassanin, Noha M.
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- Reaction of 2-Imino-2H-chromene-3-carboxamide with Phosphorus Isothiocyanates: First Synthesis of Novel Chromeno[2,3-d]pyrimidinyl and Bis(chromeno[2,3-d]pyrimidinyl)phosphines and Chromeno[2′,3′:4,5]pyrimido[2,1-d][1,3,5,2]triazaphosphinine
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Novel chromeno[2,3-d]pyrimidinyl and bis(chromeno[2,3-d]pyrimidinyl)phosphines and chromeno[2′,3′:4,5]pyrimido[2,1-d][1,3,5,2]triazaphosphinine were obtained in a simple one-pot procedure via treatment of 2-imino-2H-chromene-3-carboxamide with phenyl phosphorus isothiocyanates. Possible reaction mechanisms were proposed. The structures of the obtained products were confirmed by elemental analyses and spectral tools.
- Assiri, Mohammed A.,Ali, Tarik E.,Hassanin, Noha M.,Yahia,Sakr, Gamal B.
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p. 1646 - 1650
(2019/04/08)
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- Reaction of 2-imino-2H-chromene-3-carboxamide with phosphorus halides: Synthesis of some novel chromeno-[2,3-d][1,3,2]diazaphosphinines and chromeno[4,3-c][1,2]-azaphosphole and their antioxidant and cytotoxicity properties
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Novel 1,2-azaphosphole and 1,3,2-diazaphosphinines containing a chromene ring have been obtained from the treatment of 2-imino-2H-chromene-3-carboxamide (1) with some phosphorus halides. The compounds were evaluated for antioxidant and cytotoxic activitie
- Ali, Tarik E.,Assiri, Mohammed A.,El-Shaaer, Hafez M.,Fouda, Ahmed M.,Hassan, Mohamed M.,Hassanin, Noha M.
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p. 681 - 692
(2019/08/01)
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- Reaction of 2-imino-2H-chromene-3-carboxamide with phosphorus sulfides: Synthesis of novel 2-sulfido-2,3-dihydro-4H-chromeno[2,3-d][1,3,2]diaza-phosphinines
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Novel 2-sulfido-2,3-dihydro-4H-chromeno[2,3-d][1,3,2]diazaphosphinines are obtained in a simple one-pot procedure via treatment of 2-imino-2H-chromene-3-carboxamide with various phosphorus sulfides. Possible reaction mechanisms are proposed. The structure
- Hassanin, Noha M.,Ali, Tarik E.,El-Shaaer, Hafez M.,Hassan, Mohamed M.
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p. 651 - 655
(2018/09/25)
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- Synthesis of 2-amino-3-cyano-4H-chromene-4-carboxamide derivatives by an isocyanide-based domino conjugate addition/O-trapping rearrangement sequence
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An efficient, one-pot domino synthesis of new 2-amino-3-cyano-4H-chromene- 4-carboxamide derivatives has been developed by the acid-induced conjugate addition of isocyanides to 2-imino-2H-chromene-3-carboxamides, followed by an intramolecular O-trapping r
- Gyuris, Mario,Madacsi, Ramona,Puskas, Laszlo G.,Toth, Gabor K.,Woelfling, Janos,Kanizsai, Ivan
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experimental part
p. 848 - 851
(2011/04/15)
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- New HA 14-1 analogues: Synthesis of 2-amino-4-cyano-4H-chromenes
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The synthesis of 2-amino-4-cyano-4H-chromene derivatives as new HA 14-1 analogues by a simple and efficient method is reported. In addition, the reaction of 2-amino-2H-chromene-3-carbonitriles, salicylaldehydes and amines results in the formation of new c
- Moafi, Leila,Ahadi, Somayeh,Bazgir, Ayoob
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scheme or table
p. 6270 - 6274
(2011/01/04)
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- Polymer supported reagents: Novel methodology for selective and general synthesis of iminocoumarins
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A selective synthesis of iminocoumarins 3 was accomplished, starting from salicylaldehydes 1 and nitriles 2, by the use of Amberlite IRA 900 resin as a polymeric solid support. The possibility of using various arylacetonitriles enhances the synthetic vers
- Mhiri,El Gharbi,Le Bigot
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p. 3385 - 3399
(2007/10/03)
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- Structure and Reactivity of 2-Amino-3-carbamoylchromenylium Salts
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A series of 3-substituted 2-aminochromenylium salts were synthesized, and their acid dissociation constants in 50 percent ethanol were measured at 20 deg C. 2-Amino-3-carbamoylchromenylium salts showed a correlation between log Ka values and Brown-Okamoto substituent coefficient constants ?+ (ρ = 0.99, r = 0.973). The constant ?+ for the quinolizine group was estimated at -2.9. A scale of acidity (H+) was proposed for solutions of HCl in 50 vol percent ethanol at 20 deg C (cHCl ,1.5 M). The effect of substituents in positions 3, 6, and 7 and methylation of the 2-amino group on the reactivity of 2-aminochromenylium salts is discussed.
- Rubtsov, M. I.,Lukatskaya, L. L.,Karasev, A. A.
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p. 134 - 137
(2007/10/03)
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- Recyclization of 2-imino-2H-1-benzopyrans using nucleophilic reagents 3. Reaction of 2-iminocoumarin-3-carboxamides with o-phenylenediamines and o-amino(thio)phenols
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Using o-phenylenediamines, o-aminophenol or o-aminothiophenol, 2-iminocoumarin-3-carboxamide can be recyclized to the corresponding 3-(1H-benzimidazol-2-yl), 3-(benzoxazol-2-yl), or 3-(benzothiazol-2-yl) coumarins. An alternative synthesis has been carried out and an analytical comparison of the synthetic routes made.
- Kovalenko,Vasil'ev,Sorokina,Chernykh,Turov,Rudnev
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p. 1412 - 1415
(2007/10/03)
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- Recyclization of 2-imino-2H-1-benzopyrans under the influence of nucleophilic reagents. 2. Reaction of 2-iminocoumarin-3-carboxamides with o-aminobenzenesulfonamide
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2-Iminocoumarin-3-carboxamides recyclized into 3-(1,1-dioxo-2H-benzo-1,2,4-thiadiazinyl-3)coumarins under the influence of o-aminobenzenesulfonamide. An alternative method of synthesis is discussed. Proposed mechanisms for the recyclization are discussed.
- Kovalenko,Chernykh,Shkarlat,Ukrainets,Gridasov,Rudnev
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p. 791 - 795
(2007/10/03)
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- Recyclization of 2-imino-2H-1-benzopyrans under the influence of nucleophilic reagents. 1. New approach to the synthesis of 3-(1,3,4-oxadi-, thiadi-, and triazolyl-2)coumarins
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It has been found that under the action of hydrazides of carboxylic acids, 2-iminocoumarin-3-carboxamides are recydized to N(1)-acylamidrazones of coumarin-3-carboxylic acids. The use of N(1)-acylamidrazones is proposed as a simple and effective means of synthesizing 3-(1,3,4-oxadi-, thiodi-, and triazolyl-2)coumarins. The possibilities of alternate schemes of synthesis are discussed, and a mechanism is suggested for the recyclization. 1996 Plenum Publishing Corporation.
- Kovalenko,Zubkov,Chernykh,Turov,Ivkov
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p. 163 - 168
(2007/10/03)
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- Bicyclic compounds as ring-constrained inhibitors of protein-tyrosine kinase p56(lck)
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A study was undertaken to prepare inhibitors of the lymphocyte protein- tyrosine kinase p56(lck). Using the known p56(lck) inhibitor 3,4-dihydroxy- α-cyanocinnamamide (4) as a lead compound, bicyclic analogues were designed as conformationally constrained
- Burke Jr.,Lim,Marquez,Li,Bolen,Stefanova,Horak
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p. 425 - 432
(2007/10/02)
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