- Modelling and Phenotypic Screening of NAP-6 and 10-Cl-BBQ, AhR Ligands Displaying Selective Breast Cancer Cytotoxicity in Vitro
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To exploit the interaction of the aryl hydrocarbon receptor (AhR) pathway in developing breast-cancer-specific cytotoxic compounds, we examined the breast cancer selectivity and the docking pose of the AhR ligands (Z)-2-(2-aminophenyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (NAP-6; 5) and 10-chloro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (10-Cl-BBQ; 6). While the breast cancer selectivity of 5 in vitro is known, we discuss the SAR around this lead and, by using phenotypic cell-line screening and the MTT assay, show for the first time that 6 also presents with breast cancer selectivity, notably in the triple-negative (TN) receptor breast cancer cell line MDA-MB-468, the ER+ breast cancer cell lines T47D, ZR-75-1 and the HER2+ breast cancer cell line SKBR3 (GI50 values of 0.098, 0.97, 0.13 and 0.21 μM, respectively). Indeed, 6 is 55 times more potent in MDA-MB-468 cells than normal MCF10A breast cells (GI50 of 0.098 vs 5.4 μM) and more than 130 times more potent than in cell lines derived from pancreas, brain and prostate (GI50 of 0.098 vs 10–13 μM). Molecular docking poses of 5 and 6 together with analogue synthesis and phenotypic screening show the importance of the naphthalene moiety, and an ortho-disposed substituent on the N-phenyl moiety for biological activity.
- Baker, Jennifer R.,Pollard, Brett L.,Lin, Andrew J. S.,Gilbert, Jayne,Paula, Stefan,Zhu, Xiao,Sakoff, Jennette A.,McCluskey, Adam
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p. 1499 - 1512
(2021/03/03)
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- Montmorillonite-KSF-catalyzed synthesis of 4-heteroarylidene-N-arylhomophthalimides by Knoevenagel condensation
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A simple, efficient and rapid method for clay-catalyzed Knoevenagel condensation of heterocyclic aldehydes with active methylene compound under reflux condition is reported. This protocol offers high yield, shorter time and simple work procedure. The protocol does not require column chromatography for purification, and the process is environmentally benign.
- Krishnakumar, Varadhan,Khan, Fazlur-Rahman Nawaz,Mandal, Badal Kumar,Jeong, Euh-Duck,Jin, Jong Sung
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p. 5509 - 5519
(2015/07/08)
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- Microwave promoted one-pot synthesis of some novel N-aryl isoquinoline derivatives
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Homophthalic anhydride 1 reacts with different aromatic amines to produce N-substituted homophthalimides 2 under microwave irradiation. A rapid microwave-assisted chemical synthesis of condensed 4-substituted furo[2,3-c]isoquinoline-1,5(2H,4H)-diones 3 an
- Havaldar, Freddy H.,Mule, Ganesh B.,Dabholkar, Bhushan V.
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p. 828 - 837
(2013/08/23)
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- Flower-shaped ZnO nanoparticles as an efficient, heterogeneous and reusable catalyst in the synthesis of N-arylhomophthalimides and benzannelated isoquinolinones
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A simple and green protocol, developed utilizing an efficient, heterogeneous and recyclable catalyst, i.e. zinc oxide nanoparticles (ZnO NPs)-mediated synthesis of N-arylhomophthalimides and benzannelated isoquinolinones, is reported. The structures of th
- Krishnakumar, Varadhan,Kumar, Kesarla Mohan,Mandal, Badal Kumar,Khan, Fazlur-Rahman Nawaz
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p. 1881 - 1892
(2013/02/22)
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- Progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton
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Novel non-steroidal progesterone receptor antagonists with a 3-phenylquinazoline-2,4-dione/2-phenylisoquinoline-1,3-dione skeleton were developed and their structure-activity relationships were investigated. Among the prepared compounds, 4-(4,4-diethyl-3,
- Nakagawa, Aya,Uno, Shigeyuki,Makishima, Makoto,Miyachi, Hiroyuki,Hashimoto, Yuichi
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p. 7046 - 7054
(2008/12/22)
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- Benzoheterocyclic fungicides
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Compounds of any one of formulae I - VII where, ....is a single or double bond;, A is oxygen or sulphur;, R1 is aryl;, R2 is 1-imidazolyl or 1,2,4-triazol-1-yl; and, R3, R4, R5 and R6 which may be the same or different, ar
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- Fungicides
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Compounds of any of one of formulae I-VII STR1 where is a single or double bond; A is oxygen or sulphur; R1 is aryl; R2 is 1-imidazolyl or 1,2,4-triazol-1-yl; and R3, R4, R5 and R6, which m
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