Chalcone-4’-sulfonyl Derivatives

Recognizing the potent anticancer activities of both chalcone and sulfonamide moieties, we offer our in-house design and synthesis of novel hybrid compounds that integrate the two structures: chalcone-4’-sulfonyl chlorides and fluorides. The structural diversity of these building blocks is controlled by highly variable substituents at the styrene ring. Representative structures of the synthesized chalcone-4’-sulfonyl halides are given in Figure 2.

Our expertise enables us to create these innovative hybrid compounds, providing unique opportunities to advance drug discovery and development in these critical areas.

Please, contact us at orders@lifechemicals.com for any additional information and price quotations.

Further exploring our related products and services will make your search even more rewarding:

• Custom Synthesis Services
• Building Blocks
• Anticancer Screening Compound Libraries

Please refer to our MedChem blog on Building Blocks and Custom synthesis for related topics.

Chalcones and sulfonamides in drug discovery

Functionalized benzylidene acetophenones, commonly known as chalcones (or 1,3-diaryl-2-propen-1-ones), are an important class of natural products found in a wide variety of sources, including spices, tea, fruits, and vegetables. The chalcone substructure (Fig. 1) is a recurring motif in many marketed drugs, investigational compounds, and other biologically active molecules.

Recently, chalcones have attracted significant interest due to their diverse pharmacological properties, such as anticancer, antibacterial, antifungal, anti-inflammatory, antimalarial, and antidiabetic activities [1-6]. These compounds are valuable building blocks for introducing conjugated motifs of a carbonyl group and a carbon-carbon double bond into potential drug candidates, such as covalent inhibitors or monomers for synthetic polymers [7-8]. Thus, developing reliable methods for synthesizing chalcone-containing building blocks is crucial in both drug discovery and materials chemistry.

Research on anticancer chalcones highlights the potential of molecular hybridization to enhance anticancer efficacy, particularly through conjugation with other pharmacologically relevant scaffolds. Among these, sulfonamides stand out as one of the most significant structural classes in drug design, exhibiting a wide range of biological activities, including anticancer, antibacterial, and antimalarial properties [9-11].

Figure 1. Structure and aromatic carbon atom numbering scheme of the parent chalcone.

Figure 2. Examples of synthesized chalcone-4’-sulfonyl chlorides and fluorides.

Reference:

1. Syam S, Abdelwahab SI, Al–Mamary MA, Mohan S. Synthesis of chalcones with anticancer activities. Molecules. 2012;17:6179–95.
2. Nielsen SF, Boesen T, Larsen M, Schønning K, Kromann H. Antibacterial chalcones–bioisosteric replacement of the 4’–hydroxy. Bioorg. Med. Chem. 2004;12:3047–54.
3. Lahtchev KL, Batovska DI, Parushev SP, Ubiyvovk VM, Sibirny AA. Antifungal activity of chalcones: A mechanistic study using various yeast strains. Eur. J. Med. Chem. 2008;43:2220–8.
4. Yadav HL, Gupta P, Pawar RS, Singour PK, Patil UK. Synthesis and biological evaluation of the anti-inflammatory activity of 1,3 diphenyl propenone derivatives. Med. Chem. Res. 2011;20:461–5
5. Motta LF, Gaudio AC, Takahata Y. Quantitative structure-activity relationships of a series of chalcone derivatives (1,3–Diphenyl–2–propen–1–one) as anti plasmodium falciparum agents (anti-malaria agents) Internet Electron J. Mol. Des.2006;5:555–69
6. Hsieh CT, Hsieh TJ, El–Shazly M, Chuang DW, Tsai YH, Yen CT, Wu SF, Wu YC, Chang FR. Synthesis of chalcone derivatives as potential antidiabetic agents. Bioorg. Med. Chem. Lett.2012;22:3912–5
7. (a) Ostrem, J. M.; Peters, U.; Sos, M. L.; Wells, J. A.; Shokat, K. M. Nature 2013, 503, 548. (b) Lewis, H. D.; Liddle, J.; Coote, J. E. et al. Nat. Chem. Biol. 2015, 11, 189.
8. van Heijst, J,; Corda, M.; Lukin, O. Polymer 2015, 70, 1.
9. Supuran CT, Casini A, Scozzafava A. Protease inhibitors of the sulfonamide type: anticancer, anti-inflammatory, and antiviral agents. Med. Res. Rev. 2003;23:535–58
10. Massah AR, Adibi H, Khodarahmi R, Abiri R, Majnooni MB, Shahidi S, Asadi B, Mehrabi M, Zolfigol MB. Synthesis, in vitro antibacterial and carbonic anhydrase II inhibitory activities of N–acyl sulfonamides using silica sulfuric acid as an efficient catalyst under both solvent–free and heterogeneous conditions. Bioorg. Med. Chem.2008;16:5465–72.
11. Ryckebusch A, Dѐprez–Poulain R, Debreu–Fontaine MA, Vandaele R, Mouray E, Grellier P, Sergheraerta C. Parallel synthesis and antimalarial activity of a sulfonamide library. Bioorg. Med. Chem. Lett. 2002;12:2595–8