Synthesis of Phthalimide Imine Derivatives as a Potential Anticancer Agent

Abstract

The outstanding evidence of phthalimide pharmacophore in securing enhanced biological activities had encouraged further research and development into phthalimide-based derivatives as potential new drugs. In this study, phthalimide core was hybridized with aldehydes giving integrated imines displaying different types of functionalities and at alternating positions. The resulting compounds, therefore, provide an innovative window to explore possible differential biological effects as antioxidants and anticancer agents. A total of sixteen compounds were synthesized, and each was verified by FT-IR, H NMR, C NMR, and MS characterization. Herein, a facile single-step synthesis method was employed substituting the conventional two-step chemical production routes. Among the sixteen tested compounds, the H7 compound with hydroxyl phenolic group has shown an eminent antioxidant activity with a 19.52% decrease to the IC50 value compared to that of the control standard BHT antioxidant. On the other hand, the halogenated H6 Schiff base structure was successful in securing effective cancer inhibition to both colon and breast cancer cell lines, while maintaining selective action toward normal tissues. Results have collectively indicated the importance and impactful effects of functional groups position and types within similar basic structures, in directing different biological outcomes.

The 2-hydroxy-3-(4-aryl-1-piperazinyl)propyl Phthalimide Derivatives as Prodrugs—Spectroscopic and Theoretical Binding Studies with Plasma Proteins

“…They are a kind of hybrid of elements determining the desired course of action. The phthalimide pharmacophore, due to the presence of the -CO-N (R) -CO-fragment and an aryl hydrophobic ring, a hydrogen bond donor, electron donors, and other distal substituent donor sites on the imide nitrogen atom, allows it to bind to many biological targets [13,14]. In the structure of the tested F1-F4 derivatives, we combined the isoindole-1,3-dione skeleton and the 2-hydroxy-3-(N-aryl-piperazine)propyl group, which in the case of 3,4-pyridine dicarboxyimides, guaranteed strong analgesic properties, comparable to the action of morphine [15].…”

Benzylic C(sp3)–H Bonds Play the Dual Role of Starting Material and Oxidation Inhibitor for Hydrazides in the Electrochemical Synthesis of Hydrazones

“…13 C­{ 1 H} NMR (125 MHz, CDCl 3 ) δ 165.1, 158.6, 134.6, 134.3, 133.6, 131.7, 130.3, 128.7, 128.4, 123.7. Known compound …”

“…Known compound. 70 4-Methyl-N′-(propan-2-ylidene)benzenesulfonohydrazide (3x). Colorless solid, (32.5 mg) 72% yield, mp: 156−158 °C, 1 H NMR (500 MHz, CDCl 3 ) δ 7.84 (d, J = 7.8 Hz, 2H), 7.28 (d, J = 7.8 Hz, 2H), 2.40 (s, 3H), 1.89 (s, 3H), 1.79 (s, 3H).…”

Synthesis, characterization and preliminary antimicrobial study of some new phthalimide phenyl hydrazide derivatives

“…There are many phthalimide derivatives as potential anticancer agents. 5 Recent studies on the biological activity of phthalimide and several of its derivatives show that they possess significant biological activity that seem equivalent to or even greater than those of recognized pharmaceutical compounds. 6 Phthalimide derivatives are given a biological activity via the imide ring and structural core (-CO-N(R)-CO-).…”