Multi-Armed 1,2,3-Selenadiazole and 1,2,3-Thiadiazole Benzene Derivatives as Novel Glyoxalase-I Inhibitors

Abstract

Glyoxalase-I (Glo-I) enzyme was established to be a valid target for anticancer drug design. It performs the essential detoxification step of harmful byproducts, especially methylglyoxal. A robust computer-aided drug design approach was used to design and validate a series of compounds with selenium or sulfur based heterorings. A series of in-house multi-armed 1,2,3-selenadiazole and 1,2,3-thiadiazole benzene derivatives were tested for their Glo-I inhibitory activity. Results showed that these compounds bind Glo-I active sites competitively with strong potential to inhibit this enzyme with IC50 values in micro-molar concentration. Docking poses revealed that these compounds interact with the zinc atom at the bottom of the active site, which plays an essential role in its viability.

Polyunsaturated sulfur/selenium-containing products based on regio- and stereoselective nucleophilic addition and substitution reactions of 1,2-bis[(Z)-2-(vinylsulfanyl)ethenyl] diselane

“…Some organoselenium compounds, including diselenides, are considered as potential anti-cancer drugs. 25–33…”

“…[20][21][22][23][24] Some organoselenium compounds, including diselenides, are considered as potential anti-cancer drugs. [25][26][27][28][29][30][31][32][33] A range of selenium-containing compounds are known to exhibit antioxidant [34][35][36] and antidepressant properties. [37][38][39][40][41] Functionalized organoselenium compounds show antibacterial and antiviral activity.…”

“…CF = 8.0 Hz, C-2,6), 160.60 ( 1 J CF = 245.9 Hz, C-4); 19 F (376 MHz, CDCl 3 ): d = À114.91 ( 3 J FH(3,5) = 8.7 Hz, 4 J FH(2,6) = 5.4 Hz); 77 Se (76 MHz, CDCl 3 ): d = 327.75, 327.79 ( 6 J FSe = 3.7 Hz); EI-MS m/z (%): 274 (9, M + ), 165 (3), 151(25), 109 (100), 83(18), 59(10), 58 (8); anal. calcd for C 11 H 11 FSSe: C, 48.35; H, 4.06.…”

Synthesis, Characterization, and Antioxidant, Antimicrobial and Toxic Properties of Novel Δ2 -1,3,4-thiadiazoline and Δ2 -1,3,4-selenadiazoline Derivatives

“…1 Thus, several heterocycles containing sulfur, selenium, and nitrogen atoms were prepared which are useful substrates for the preparation of various heterocyclic systems. 2 There is a rapidly growing interest for creating several chemotherapeutic agents due to the limitations of the existences drugs to cure and improve survival in many diseases. 3 Sulphur or selenium is a key component of several major metabolic pathways in human, including thyroid hormone metabolism, antioxidant defence system, and immune function.…”

Computational Structure Characterization of 1,2,3-Selendiazole Isomers, Investigation of Some Molecular Properties and Biological Activities

“…As in the nature of most chemicals, differences in functional groups have created differences in their biological potentials. 1,2,3-selenadiazole derivatives act as microbial agents such as antifungal [3], antibacterial [4], antitumor [5], cytotoxic [6] and enzyme inhibitors [7], as well as having important applications in chemotherapy and pharmacology [3][4][5][6][7]. In particular, the benzopyrano-1,2,3-selenadiazole derivatives exhibited antitumor activity against human cell lines such as MCF-7, VERO (African green monkey kidney cells), WI-38 (fibroblast cells) and HEPG-2 (hepatoma cells) [5].…”