In vitro mutagenic, antimutagenic, and antioxidant activities evaluation and biotransformation of some bioactive 4‐substituted 1‐(2‐methoxyphenyl)piperazine derivatives

Abstract

In vitro mutagenic, antimutagenic, and antioxidant potency evaluation and biotransformation of six novel 4-substituted 1-(2-methoxyphenyl)piperazine derivatives demonstrating antidepressant-like activity were investigated. Mutagenic and antimutagenic properties were assessed using the Ames test; free radical scavenging activity was evaluated with 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay and biotransformation was performed with liver microsomes. It was found that all tested compounds are not mutagenic in bacterial strains TA100 and TA1535 and exhibit antimutagenic effects in the Ames test. Noteworthy, compounds possessing propyl linker between phenoxyl and N-(2-methoxyphenyl)piperazine displayed more pronounced antimutagenic properties than derivatives with ethoxyethyl linker. Additionally, compounds 2 and 6 in vitro biotransformation showed that primarily their hydroxylated or O-dealkylated metabolites are formed. Some of the compounds exhibited intrinsic clearance values lower than those reported previously for antidepressant imipramine. To sum up, the results of the present study might represent a valuable step in designing and planning future studies with piperazine derivatives.

Metabolic stability and its role in the discovery of new chemical entities

“…Next, the samples are centrifuged and supernatants are analyzed using chromatography methods to determine the metabolic profile of the test compound. For control samples, the NADPH-regenerating system is replaced by phosphate buffer (2,31,(66)(67)(68)(69)(70)(71)(72)(73)(74)(75)(76).…”

Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide, a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach

“…The probability of a certain atom to be a SOM depends on the accessibility of this atom toward the heme and the chemical reactivity of atom in the specific reaction. Potential metabolites are ranked according to a probability score reflecting the likelihood of being generated, where 100% represents the maximum score …”

In Vitro Biotransformation, Safety, and Chemopreventive Action of Novel 8-Methoxy-Purine-2,6-Dione Derivatives

“…Compounds 1 and 3 were studied in a biotransformation assay using rat liver microsomes following procedures described previously [ 18 – 22 ]. The reagents used in this assay were levallorphan (internal standard) and NADPH-regenerating system, which contained phosphate buffer (pH 7.4), NADP + , glucose-6-phosphate, and glucose-6-phosphate dehydrogenase [ 18 ].…”

“…The capacity of selected 8-methoxy-purine-2,6-dione derivatives to scavenge stable free radical DPPH was assessed [ 22 , 38 – 42 ]. A blank and a triplicate of 10 different concentrations of each compound or of each positive control (gallic and ascorbic acids) were evaluated in the experiment.…”