.BETA.-N-Cyanoethyl Acyl Hydrazide Derivatives: A New Class of .BETA.-Glucuronidase Inhibitors.

Abstract

Eight new b b-N-substituted acyl hydrazides along with their corresponding acyl derivatives were synthesized and screened for in vitro b b-glucuronidase inhibition and found to be active against the enzyme. All of these compounds were found to be noncompetitive inhibitors except for N-(2-cyanoethyl)-4-hydroxy benzohydrazide (10), which was found to be an uncompetitive inhibitor. Structure-activity relationship studies indicated that the benzyloxy group present in compounds 12 and 13 is responsible for the b b-glucuronidase inhibition activity.

Green synthesis of new acyl hydrazide derivatives by single and double aza-Michael reaction under solvent-free conditions

“…With this established optimum conditions (acyl hydrazide (1.0 mmol), DABCO (1.0 mmol), TBAB (1.0 mmol) and fumaric esters (1.2 mmol)), we were keen to explore the scope of the reaction with respect to other fumaric esters and acyl hydrazides, whose results are depicted in Table 3 (entries [8][9][10][11][12].…”

“…Their synthesis has attracted significant attention due to their utility as building blocks in many syntheses (2)(3)(4). Most of these compounds show interesting properties such as antituberculous agent (Isoniazid), HIV inhibitors, inhibitors of myeloperoxidase, glycogen phosphorylase, pesticides (5-7) and β-glucuronidase enzyme inhibitors (8). Also, these compounds have analgesic activity (9) and acyl hydrazides have been known as novel inhibitors of mammalian cathepsin B and cathepsin H (10).…”

Inhibitory Effect of Heat-Treated 3-(3^|^prime;,4^|^prime;-dihydroxyphenyl)-L-alanine (DOPA) on ^|^beta;-glucuronidase Activity

“…Some of the conjugates escape excretion and are transferred to the intestinal tract via bile. These conjugates can be degraded by bacterial β-glucuronidase (EC 3.2.1.31), an exoglycosidase enzyme that catalyzes the cleavage of glucuronosyl-O bonds (Khan et al, 2002) and resides in the intestinal tract, to liberate potentially carcinogenic compounds (Freeman, 1986;Knasmüller et al, 2001). High fecal β-glucuronidase activities have been associated with an increased risk of colon cancer (Rafter et al, 2004).…”

Kinetic and thermodynamic study of inter‐ and intramolecular proton transfer in N′‐acetyl formohydrazide tautomers

“…AHs can be used in pharmaceutical chemistry [2][3][4] synthesis of novel heterocyclic compounds [5,6], synthesis of inhibitors for antiparasitic activity against Trypanosoma brucei [7], diastreoselective synthesis [8], photochemical reactions [9], preparation of antigens [10], and many other applications [11][12][13][14][15][16][17][18]. Nine different tautomers and 11 possible tautomerism interconversions can be assigned to these compounds.…”