- Photochemical transformation of flufenamic acid by artificial sunlight in aqueous solutions
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In the present article, we have studied the photochemical behavior of a common non-steroidal anti-inflammatory drug (NSAIDs) namely flufenamic acid (FLUA) in aqueous solution. The absorption spectrum of such compound shows a significant absorption beyond
- Rafqah, Salah,Sarakha, Mohamed
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- Development of potent and selective inhibitors of aldo-keto reductase 1C3 (type 5 17β-hydroxysteroid dehydrogenase) based on N -phenyl-aminobenzoates and their structure-activity relationships
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Aldo-keto reductase 1C3 (AKR1C3; type 5 17β-hydroxysteroid dehydrogenase) is overexpressed in castration resistant prostate cancer (CRPC) and is implicated in the intratumoral biosynthesis of testosterone and 5α-dihydrotestosterone. Selective AKR1C3 inhibitors are required because compounds should not inhibit the highly related AKR1C1 and AKR1C2 isoforms which are involved in the inactivation of 5α-dihydrotestosterone. NSAIDs, N-phenylanthranilates in particular, are potent but nonselective AKR1C3 inhibitors. Using flufenamic acid, 2-{[3-(trifluoromethyl)phenyl]amino}benzoic acid, as lead compound, five classes of structural analogues were synthesized and evaluated for AKR1C3 inhibitory potency and selectivity. Structure-activity relationship (SAR) studies revealed that a meta-carboxylic acid group relative to the amine conferred pronounced AKR1C3 selectivity without loss of potency, while electron withdrawing groups on the phenylamino B-ring were optimal for AKR1C3 inhibition. Lead compounds did not inhibit COX-1 or COX-2 but blocked the AKR1C3 mediated production of testosterone in LNCaP-AKR1C3 cells. These compounds offer promising leads toward new therapeutics for CRPC.
- Adeniji, Adegoke O.,Twenter, Barry M.,Byrns, Michael C.,Jin, Yi,Chen, Mo,Winkler, Jeffrey D.,Penning, Trevor M.
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p. 2311 - 2323
(2012/05/04)
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- 2,7-Dihydro-3H-pyridazino[5,4,3-kl]acridin-3-one derivatives, novel type of cytotoxic agents active on multidrug-resistant cell lines. Synthesis and biological evaluation
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We have earlier postulated that the presence of a pyridazone ring fused with an anthracenedione moiety resulted in the analog's ability to overcome multidrug resistance of tumor cells [J. Med. Chem. 1999, 42, 3494]. High cytotoxic activity of obtained ant
- Stefanska, Barbara,Bontemps-Gracz, Maria M.,Antonini, Ippolito,Martelli, Sante,Arciemiuk, Malgorzata,Piwkowska, Agnieszka,Rogacka, Dorota,Borowski, Edward
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p. 1969 - 1975
(2007/10/03)
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- Synthesis and evaluation of anthranilic acid-based transthyretin amyloid fibril inhibitors
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Eight small molecules were synthesized to evaluate the structure activity relationships (SAR) of N-substituted anthranilic acids. The molecules were synthesized by benzylation or arylation of methyl anthranilate. A light scattering-based amyloid fibril formation assay was used to evaluate potential inhibitors of transthyretin (TTR) amyloid fibril formation in vitro. The m-carboxyphenylated and o-trifluoromethylphenylated anthranilic acids are potent inhibitors that will be subjected to further SAR and structural analysis.
- Oza, Vibha B.,Petrassi, H. Michael,Purkey, Hans E.,Kelly, Jeffery W.
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- Structure-activity relationship of quinazolinedione inhibitors of calcium-independent phosphodiesterase
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A series of quinazolinediones and azaquinazolinediones is described which possess potent inhibitory activity toward the calcium-independent phosphodiesterase enzyme (CaIPDE). In vivo testing showed that this in vitro activity translates to animal models p
- Lowe III,Archer,Chapin,Cheng,Helweg,Johnson,Koe,Lebel,Moore,Nielsen,Russo,Shirley
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p. 624 - 628
(2007/10/02)
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