Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors

Abstract

In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a–19a and 1b–19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms.

First Examples of Reactions of 3-Trimethylsilyl-2-Propynamides and Organic Diselenides: Synthesis of Novel Derivatives of Propynamides

“…Organoselenium compounds exhibit a variety of biological activities [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] including antitumor [10][11][12][13], antibacterial [13,14], antiviral [15,16] and glutathione peroxidase mimetic properties [17][18][19].…”

“…77 Se NMR (76.3 MHz, CDCl3): δ 477.0, 482.2. 15 N NMR (40.6 MHz, CDCl3): δ −262.7 (N), −256.4 (N'); The 2D 15 N NMR HMBC { 1 H-15 N} spectrum contains cross-peaks of nitrogen atoms with H 3',5' and H 2,6 protons.MS, m/z: 577 (9) [M], 279(10), 277(8), 220(20), 218(28), 161(18), 159(11), 140(42), 138(44), 135(15), 133(12), 114(40), 112(19), 86 (69), 84 (100), 70 (56), 69(24), 57(30), 56 (66), 55(36), 44(13), 42(38), 41(34).Anal. calcd for С22H33N3O5Se2 (577.43): C 45.78, H 5.76, N 7.28, Se 27.35; found: C 46.07, H 5.95, N 6.97, Se 27.05.…”

“…, 138(44), 135(15), 133(12), 114(40), 112(19), 86 (69), 84 (100), 70 (56), 69(24), 57(30), 56 (66), 55(36), 44(13), 42(38), 41(34).Anal. calcd for С22H33N3O5Se2 (577.43): C 45.78, H 5.76, N 7.28, Se 27.35; found: C 46.07, H 5.95, N 6.97, Se 27.05.…”

“…2,6 protons. , 138(44), 135(15), 133(12), 114(40), 112(19), 86 (69), 84 (100), 70 (56), 69(24), 57(30), 56 (66), 55(36), 44(13), 42(38), 41(34). Anal.…”

Efficient Regioselective Synthesis of Novel Ensembles of Organylselanyl-Functionalized Divinyl Sulfides and 1,3-Thiaselenoles under Phase Transfer Catalysis Conditions

“…To date, many classes of organoselenium compounds have been studied, and promising products, especially selenium heterocycles, have been found that exhibit various kinds of biological activities [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] including antiviral [13,14], antibacterial [11,12], antitumor [8][9][10][11], and glutathione peroxidase-like properties [15][16][17].…”