Design, synthesis, biological evaluations, molecular docking, and in vivo studies of novel phthalimide analogs

Abstract

A series of novel phthalimide analogs containing an indole or brominated indole moiety were synthesized and their antimicrobial activity was evaluated. Compound 8 showed a broad spectrum activity, revealing 53-67% of erythromycin activity on the tested bacteria and 60-70% of miconazole activity on the tested fungi. Anticancer activity was evaluated on the cell lines HepG2, MCF-7, A549, H1299, and Caco2. The results revealed that the new phthalimide analog 8 has broad-spectrum anticancer activity toward all the tested cancer cell lines, followed by compound 11, which showed good activity toward all the tested cell lines except for MCF-7. The ability of the promising analogs 5, 8, and 11 to bind to topoisomerase II DNA gyrase was investigated. Caspase-3 activation and Bcl-2 assay of the best active derivatives 8, 11 in addition to compound 5 were evaluated. The antifibrotic activity was studied in an in vivo model and the histopathological studies revealed that treatment with the new compound 8 improved the fibrotic liver tissues to normality.

New phthalimide analog ameliorates CCl4 induced hepatic injury in mice via reducing ROS formation, inflammation, and apoptosis

“…The chemical structure of phthalimide analog was confirmed as previously reported by Zahran et al, 2018 . In brief, the 1 H NMR spectrum of phthalimide analog, 2-[2-(2-Bromo-1-ethyl-1H-indol-3-yl) ethyl]-1H-isoindole-1,3(2H)-dione revealed the following data: 1 H NMR (DMSO‑ d 6 , 300 MHz), δ ppm: 1.13 (t, J = 7.2 Hz, 3H), 3.02 (t, J = 7.2 Hz, 2H), 3.79 (t, J = 6.9 Hz, 2H), 4.19 (q, J = 6.9 Hz, 2H), 7.02 (t, J = 7.2 Hz, 1H), 7.13 (t, J = 7.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H), 7.54 (d, J = 8.1 Hz, 1H), 7.81 (s, 4H) as showed in Fig.…”

“…Phthalimide analog was prepared according to Zahran et al, 2018 . In brief, a solution of isoindole (1) in dry dimethylformamide (DMF), sodium hydride (NaH) was added and kept stirring for 30 min, then ethyl bromide was added.…”

“…Numerous N-substituted phthalimide-based drug analogs with potent anticancer therapeutic activities were stated ( Guirgis et al, 2010 , El-Aarag et al, 2014 , El-Aarag et al, 2017 ). Also, recent phthalimide-indole derivatives with several biodiversity were reported ( Zahran et al, 2018 ).…”

Synthesis, Characterization, and In Vivo Anti-Cancer Activity of New Metal Complexes Derived from Isatin-N(4)antipyrinethiosemicarbazone Ligand Against Ehrlich Ascites Carcinoma Cells

“…Defects in apoptosis mechanisms can induce tumor pathogenesis [78], for example, the activation of caspases by the signal transduction pathway can lead to irreversible apoptosis through protein degradation [79]. Therefore, it is important to design and develop new agents that act as caspases activators to treat cancers [80,81]. Consequently, the effect of ligand 1 and its metal complexe 2 , 7 and 9 on the stimulation of caspase-7 was examined in tumor and liver tissues of EAC mice.…”

Design, Synthesis and Biological Evaluation of Novel Indole-Thalidomide Hybrids Analogs

“…Therefore, the research for new cancer-treating agents is an important area in both organic and medicinal chemistry. Indoles are the main components of many drugs and some biologically active compounds, and the development of new forming methods leading to indole derivatives has attracted much attention in organic synthesis Recently, our group synthesizes novel indole, phthalimide, thalidomide analogs and studies intensively their antitumor activity [36][37][38][39][40][41][42][43][44][45]. Based on the previously mentioned facts, the current study aimed to synthesize novel Thalidomide-Indole hybrids by Knoevenagel condensation between 1Hindole-3-carbaldehyde and different active methylene Compounds.…”