Design, Synthesis, and Antitumor Activity of a Series of Novel 4-(Aromatic Sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-ones

Abstract

Many sulfonamides show anticancer activity. Based on benzenesulfonylazaspirodienone (HL-X9) identified in our previous work, we optimized the lead compound for better efficacy, thereby synthesizing a series of novel 4-(aromatic sulfonyl)-1-oxa-4-azaspiro[4.5]deca-6,9-dien-8-one derivatives through a key step of metal-catalyzed cascade cyclization. The preliminary antiproliferative tests have shown that the anticancer activities of acetyl-protected mannose-linked sulfonylazaspirodienone derivatives (7i–7l) have been greatly improved. Among them, 7j is the most potent derivative, with IC50 values of 0.17 µM, 0.05 µM, and 0.07 µM for A549, MDA-MB-231, and HeLa cell lines, respectively. Flow cytometry analysis shows that 7j arrests MDA-MB-231 cells in the G2/M phase and has a certain effect on the apoptosis of MDA-MB-231 cells. In addition, the acute toxicity of 7j was lower than that of adriamycin.

Synthesis, Molecular Docking, and Antitumor Evaluation of Some New Pyrazole, Pyridine, and Thiazole Derivatives Incorporating Sulfonamide Residue

“…1). In addition, Sulfonyl or sulfonamide hybrids were broadly explored for their anticancer activities via different mechanisms [8][9][10][11][12][13][14][15][16][17] and it was found that they possess minimum side effects along with multi-drug resistance activity. Therefore, and in continuation of our interest to develop a series of novel small molecules as potential antitumor agents that can block biologically relevant molecular targets [18][19][20][21][22] , we prepared certain pyrazoles, pyridines, thiazoles derivatives containing sulfonamide pharmacophores and studied their activity against breast cancer cell line (MCF-7).…”

New Insights Into the Promising Antibacterial Activity of Thiophene or Chromene Moiety Containing Aryl Sulfonamide

“…37 As a result, it is viable to expand a sequence of sulfonamides with alkyl amide side chain amendment on carboxyl for enhanced antibacterial e ciency. Sulfonamides have medicinal applications and many of them are broadly utilized in therapeutic as antimicrobial 38 , antitumor [39][40] , anticancer 41 , antiviral 42 , anti-HIV 43 , antidiabetic 44 , antimalarial 45 , antitubercular 46 , analgesic 47 , antioxidant 48 , antihypertensive 49 , antileishmanial 50 , anti-in ammatory 51 , anticonvulsant 52 , diuretic 53 , anti-carbonic anhydrase 54 and antiplatelet. 55…”

Synthesis, Molecular Docking, And Antitumor Evaluation of Some New Pyrazole, Pyridine, And Thiazole Derivatives Incorporating Sulfonamide Residue

“…1). In addition, Sulfonyl or sulfonamide hybrids were broadly explored for their anticancer activities via different mechanisms [8][9][10][11][12][13][14][15][16][17] and it was found that they possess minimum side effects along with multi-drug resistance activity. Therefore, and in continuation of our interest to develop a series of novel small molecules as potential antitumor agents that can block biologically relevant molecular targets [18][19][20][21][22] , we prepared certain pyrazoles, pyridines, thiazoles derivatives containing sulfonamide pharmacophores and studied their activity against breast cancer cell line (MCF-7).…”