Design, synthesis, and correlation analysis of 7-substituted 4-hydroxyquinoline-3-carboxylic acids as inhibitors of cellular respiration

Abstract

Fifteen 7-substituted 4-hydroxyquinoline-3-carboxylic acids have been designed to minimize covariance between the physicochemical substituent parameters: pi, MR, and sigmap. The molecules have been synthesized and evaluated for their ability to inhibit the respiration of Ehrlich ascites cells as a whole cell model and for their ability to inhibit malate dehydrogenase as an intracellular target enzyme model. Correlation analysis indicates that ascites cell inhibition is linearly related to pi and that malate dehydrogenase inhibition is linearly related to MR.

Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

“…A solution of the appropriate aniline (100 mmol), and diethyl ethoxymethylenemalonate(20.4 mL, 100 mmol) was heated under reflux for 3 h. The mixture was allowed to cool and then was poured into ice-cold water (100 g). The precipitate was collected by filtration and recrystallized from hexane to give derivatives 8a – c [20,26,27].…”

“…Anilinomethylenemalonates 8a – c (3 g, 10.83 mmol) were refluxed for 30 min in diphenyl ether (30 mL), leading to crudeoxoquinolines 9a – c which were recrystallized from dimethylformamide [20,21,26,27].…”

Studies of Anti‐HIV Transcription Inhibitor Quinolones: Identification of Potent N1‐Vinyl Derivatives

“…Ethyl 1‐amino‐7‐fluoro‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate (27) : Starting from intermediate 23 ,12 and following the procedure used for the synthesis of compound 26 , compound 27 was obtained in 24 % yield; mp: 228–230 °C; 1 H NMR ([D 6 ]DMSO): δ =1.30 (t, J =7.0 Hz, 3 H, CH 2 CH 3 ), 4.25 (q, J =7.0 Hz, 2 H, CH 2 CH 3 ), 6.55 (br s, 2 H, NH 2 ), 7.35 (dt, J =8.9 and 2.3 Hz, 1 H, H‐6), 7.75 (dd, J =10.9 and 2.3 Hz, 1 H, H‐8), 8.25 (dd, J =8.9 and 6.2 Hz, 1 H, H‐5), 8.60 ppm (s, 1 H, H‐2).…”

“…Finally basic hydrolysis afforded the target acids 3 a–c . In an analogous manner, beginning from synthon 23 ,12 6‐hydrogen analogue 7 a–c were obtained from intermediates 27 and 31 ; while, starting from compound 24 ,13 6‐hydroxy target acids 8 a and 8 b were obtained from intermediates 28 and 32 .…”

Quantitative Structure-Activity Relationship Studies on Anticancer Drugs

“…A series of nitrogen mustards of isatins (VI) was CH2N(CH2CH2CI)2 VI synthesized and studied for their HeLa cell growth inhibition activity by Maysinger et al 54 These authors attempted to correlate this activity with log P and obtained eq 20 neglecting three compounds where Ri = N02. This exclusion and consequently obtaining a parabolic correlation based on only seven data points do not allow much confidence to be placed in eq 20. log(l/IC50) = 3.154 + 1.162 logP -0.256(logP)2 (20) n = 13, r = 0.904, s = 0.199, log P0 = 0.31 (22) 2. Nitrosoureas Nitrosoureas (VII) constitute another important class of alkylating agents possessing a variety of biologically significant effects.…”