Phthalimide analogs as probable 15-lipoxygenase-1 inhibitors: synthesis, biological evaluation and docking studies.

Abstract

BACKGROUND:

Recent studies have been explained the role of lipoxygenases (LOX) in the origin of cancer. Among the lipoxygenases, the 5-LOX, 12-LOX and 15-LOX are more important in the cause of neoplastic disorders. In the present investigation, a new series of anticancer agents with 1,3,4-thiadiazole and phthalimide substructures were synthesized and their in vitro cytotoxicity was evaluated by MTT assay. Moreover, enzyme inhibitory potency was also assessed by enzymatic protocol towards 15-LOX-1. Molecular docking was performed to explore in silico binding mode of the target compounds.

RESULTS:

Tested compounds showed a better cytotoxic activity against HT29 cell line (colorectal cancer) in comparison with other cell lines (PC3: prostate carcinoma; SKNMC: neuroblastoma). Unfortunately, all of the tested derivatives rendered lower inhibitory potency than quercetin towards 15-LOX-1. Four hydrogen bonds were detected in docking studies for compound 4d as the most potent derivative in enzymatic assay.

CONCLUSIONS:

The biological results of reported compounds in this research were not so satisfactory. But, further structural modifications are necessary to improve the bioactivity of these derivatives.

• Authors: Alireza Aliabadi, Ahmad Mohammadi-Farani, Zeinab Hosseinzadeh, Hamid Nadri, Alireza Moradi, Farahnaz Ahmadi
• Journal: Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences (Daru) Vol. 23 Pg. 36 (Jul 22 2015) ISSN: 2008-2231 [Electronic] Switzerland
• PMID: 26197788 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Lipoxygenase Inhibitors
• Phthalimides
• ALOX15 protein, human
• Arachidonate 15-Lipoxygenase

Topics

• Arachidonate 15-Lipoxygenase (metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Lipoxygenase Inhibitors (chemical synthesis, pharmacology)
• Models, Molecular
• Molecular Docking Simulation
• Phthalimides (chemical synthesis, pharmacology)
• Structure-Activity Relationship