Romanian Society of Pharmaceutical Sciences
 

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DISCOVERY OF 2-(1,3-DIOXOISOINDOLIN-2-YL)-N-PHENYL-ACETAMIDE DERIVATIVES AS PROBABLE 15-LIPOXYGENASE-1 INHIBITORS WITH POTENTIAL ANTICANCER EFFECTS

ALIREZA ALIABADI1,2*, AHMAD MOHAMMADI-FARANI3, SAEED SEYDI-KANGARSHAHI4, FARAHNAZ AHMADI3

1.Novel Drug Delivery Research Centre, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
2 .Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
3 .Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
4 .Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

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A new series of phthalimide based 15-lipoxygenase-1 inhibitors were synthesized and their cytotoxic potency was also evaluated in three cancerous cell lines. Namely, SKNMC (neuroblastoma), PC3 (prostate carcinoma) and HT29 (colorectal cancer) cell lines were applied and the obtained results were compared to doxorubicin. The obtained compounds exhibited a high inhibitory activity towards 15-lipoxygense-1 compared to quercetin as reference drug. Compound 3e with meta methoxy moiety was the most efficient one in this series (IC50 = 1.96 ± 0.2 nM). An acceptable in vitro anticancer activity was also observed especially against HT29 cell line. Compound 3d with ortho methoxy moiety demonstrated the highest cytotoxic effect against the mentioned cell line (IC50 = 80.1 nM). The most probable binding mode of the final compounds was also explored using molecular docking.