Disease relevance of alpha-Methylbenzylaminobenzotriazole

• Absorption of the activity in R alpha MB with myeloma cells, concomitantly removed reactivity with the normal stem cell, CFU-s, and the myeloma stem cell, plasmacytoma CFU-s. Sorting analysis further showed that the antigen was diminished within a positive tumor population as cells acquired the capacity to secrete immunoglobulin [1].

High impact information on alpha-Methylbenzylaminobenzotriazole

• The most potent and isozyme-selective suicide inhibitor prepared was alpha MB: at 1 microM this compound inhibited approximately 80% of isozyme 2-catalyzed and 20% of isozyme 6-catalyzed monooxygenase activity but spared P-450 isozyme 5; at 2.5 microM it caused a near-complete loss (96 +/- 2%) of BND activity [2].
• This determinant(s), which is defined by a rabbit antimouse brain antiserum (R alpha MB), is present on the tumor stem cell population of some but not all B cell neoplasms examined [1].
• Maximal complexation with the three compounds was observed in microsomes from phenobarbital-induced guinea pigs where the initial rate of complex formation was dependent upon inhibitor concentration and apparent Km values of 108 +/- 44, 338 +/- 96, and 84 +/- 15 microM for BBT, alpha MB, and alpha EB, respectively, were found [3].
• The kinetics of mechanism-based inactivation of phenobarbital-inducible rabbit hepatic cytochromes P450 2B4 and 2B5 by N-benzyl-(BBT) and N-alpha-methylbenzyl (alpha MB) 1-aminobenzotriazole were investigated using reconstituted P450 2B4, a stable heterologous expression system, and hepatic microsomes [4].
• Similar P450 2B selectivity of BBT and alpha MB in both hepatic microsomes and the stable expression system further validates this new expression system and the use of the selective markers identified for 2B4 and 2B5 in hepatic microsomes [4].

Associations of alpha-Methylbenzylaminobenzotriazole with other chemical compounds

• Incubation of hepatic microsomes for 45 min in the presence of NADPH and 10 microM BBT or alpha MB resulted in > 90% inhibition of PROD, EROD, and MROD activities [5].
• N-Benzyl-1-aminobenzotriazole and N-alpha-methylbenzyl-1-aminobenzotriazole were more potent inhibitors of monooxygenase activity than the parent compound in microsomes from untreated and phenobarbital-induced guinea pigs [6].
• The mechanism-based inactivation of hepatic cytochrome P-450 by the suicide inhibitor 1-aminobenzotriazole and two of its derivatives, N-benzyl-1-aminobenzotriazole and N-alpha-methylbenzyl-1-aminobenzotriazole, was investigated in microsomes from untreated, phenobarbital-induced, and beta-naphthoflavone-induced guinea pigs [6].
• Chemical inhibitors used to ascertain the contributions made by various cytochromes P450 were imipramine for CYP2C, alpha-methylbenzylaminobenzotriazole (MBA) for CYP2B, alpha-naphthoflavone (ANF) for CYP1A, 5-phenyl-1-pentyne (5P1P) for CYP2F2, and diethyldithiocarbamate (DTTC) for CYP2E1 [7].

References