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Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

[ Vol. 17 , Issue. 4 ]

Author(s):

Ognyan I. Petrov, Yordanka B. Ivanova*, Mariana S. Gerova and Georgi Ts. Momekov   Pages 512 - 517 ( 6 )

Abstract:


Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments.

Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined.

Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration – dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable.

Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

Keywords:

chalcone, Mannich base, 2(3H)-benzoxazolone, cytotoxicity, oxazole, GSH.

Affiliation:

Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry and Pharmacy, Sofia University St. Kliment Ohridski, 1 James Bourchier Blvd., Sofia 1164, Department of Plant Pathology and Chemistry, Faculty of Ecology and Landscape Architecture, University of Forestry, 10 Kliment Ohridsky Blvd., Sofia 1756, Department of Pharmaceutical and Applied Organic Chemistry, Faculty of Chemistry and Pharmacy, Sofia University St. Kliment Ohridski, 1 James Bourchier Blvd., Sofia 1164, Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University Sofia, 2 Dunav Str., Sofia 1000



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