Biodegradability Nature of Polybenzimidazole Analogs by Modulating Two Histidine Degradation Enzymes (Urocanase and Formiminoglutamase): in silico Approach

Abstract

Biodegradation pathway of substituted imidazole compounds has been reported to have close analogue to histidine degradation pathway. The present study carried out on four different types of polybenzimidazole (PBI) analogs such as m-PBI (where n = 1, 2 and 3), p-PBI (where n = 1, 2 and 3), pyridine-m-PBI (where n = 1, 2 and 3) and alkylated-m-PBI (where n = 1, 2 and 3). These polybenzimidazole analogs were evaluated on the docking behaviour of urocanase and formiminoglutamase (FIGase) using PatchDock. Besides, molecular physico-chemical, drug-likeness, ADME (absorption, distribution, metabolism and excretion analyses) were studied. ADME analysis showed that m-PBI (where n = 1) and pyridine-m-PBI (where n = 1) predicated to have cytochrome P450 (CYP1A2, CYP2C19, CYP2D6 and CYP3A4) inhibition effect. Docking studies revealed that alkylated-m-PBI (where n = 2) showed the least atomic contact energy (-123.83 kcal/mol) with that of urocanase. Similarly, m-PBI (where n = 1) showed the least ACE (-123.83 kcal/mol) with that of formiminoglutamase.

Pharmacokinetics, dynamics, toxicology and molecular docking of bioactive alkaloid vasicine from Adhatoda vasica: a promising toxin binder against aflatoxin B1 and ochratoxin A

“…In the case of drug likeness if the score >0 was considered active, -5.0 to -0.0 as moderate active, and <-5.0 as inactive ( Veeraragavan et al, 2018 ).…”