Design, Synthesis, Crystal Structure, In Vitro and In Silico Evaluation of New N′-Benzylidene-4-tert-butylbenzohydrazide Derivatives as Potent Urease Inhibitors

Abstract

Hydrazides play a vital role in making biologically active compounds in various fields of chemistry. These determine antioxidant, antidepressant, antimalarial, anti-inflammatory, antiglycating, and antimicrobial activity. In the present study, twenty-three new N’ benzylidene-4-(tert-butyl)benzohydrazide derivatives (4–26) were synthesized by the condensation of aromatic aldehydes and commercially available 4-(tert-butyl)benzoic acid. All the target compounds were successfully synthesized from good to excellent yield; all synthesized derivatives were characterized via spectroscopic techniques such as HREI-MS and 1H-NMR. Synthesized compounds were evaluated for in vitro urease inhibition. All synthesized derivatives demonstrated good inhibitory activities in the range of IC50 = 13.33 ± 0.58–251.74 ± 6.82 µM as compared with standard thiourea having IC50 = 21.14 ± 0.425 µM. Two compounds, 6 and 25, were found to be more active than standard. SAR revealed that electron donating groups in phenyl ring have more influence on enzyme inhibition. However, to gain insight into the participation of different substituents in synthesized derivatives on the binding interactions with urease enzyme, in silico (computer simulation) molecular modeling analysis was carried out.

Unveiling potent Schiff base derivatives with selective xanthine oxidase inhibition: In silico and in vitro approach

“…ADMET screening studies have been recognized as fundamental concepts and key tools that were integrated early in the drug discovery phase. These studies served to assist modern project teams in predicting human pharmacokinetics and evaluating the potential of drugs ( Lin et al, 2003 , Ahmad et al, 2022a , Ahmad et al, 2022b ). Different parameters were chosen for ADMET calculations to determine the flux of the best inhibitors within the human body during administration.…”

“…Schiff bases play a crucial role as ligands and are among the most widely used organic substances ( Boulechfar et al, 2023 , Khan et al, 2023 , Luo et al, 2023 ). They can be considered a subclass of imines ( Ahmad et al, 2022a , Ahmad et al, 2022b , Shilpa Laxman, 2022 ), which contain the imine (-C = N-) group in their structure that occurs through the reaction of an aldehyde or ketone with a primary amine under suitable conditions ( Ahmad et al, 2022a , Ahmad et al, 2022b , Nuriye Tuna, 2022 ). The imine group can be part of the 1,2,4-triazole ring ( Jumaa et al, 2017 ).…”

Exploring the synthesis, structure, spectroscopy and biological activities of novel 4-benzylidene-1-(2-(2,4-dichloro phenyl)acetyl) thiosemicarbazide derivatives: An integrated experimental and theoretical investigation

“…The current study is based on the synthesis of novel thiosemicarbazide derivatives of 2,4-dichlorophenylacetic acid in high yields via multistep reactions. In the first step, the starting material 2,4-dichlorophenylacetic acid 1 was refluxed with sulfuric acid (H 2 SO 4 ) in absolute ethanol to get the desired ester 2 ( Ahmad et al, 2022a ). The obtained ester was further refluxed with thiosemicarbazide in the presence of catalytic amount of acetic acid in pure ethanol to get compound 3.…”

Para-Substituted Thiosemicarbazones as Cholinesterase Inhibitors: Synthesis, In Vitro Biological Evaluation, and In Silico Study

“…Thus, drugs to treat AD are based on their ability to inhibit cholinesterase enzymes, that is, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). , Nowadays, various drugs are used for the treatment of AD, including rivastigmine, donepezil, galantamine, and tacrine (Figure ). Synthetic organic chemists are working on new, chief, effective, and safe drugs for AD. , In the near past, our research group has reported imine-containing derivatives with promising biological activities. − The present work is mainly focused on the synthesis of various thiosemicarbazone derivatives with anticholinesterase inhibitory potential.…”