This study focuses on developing novel antimicrobials to combat drug-resistant pathogens, addressing compounds failing clinical trials due to inadequate physicochemical properties. Sixteen imidazolidine-4-one derivatives were synthesized by extensive evaluation using molecular docking, absorption, distribution, metabolism, excretion (ADME) predictions, and antimicrobial testing. Molecular docking studies conducted with Schrödinger's Glide revealed that compounds S4 and G8 exhibited superior docking scores of -7.839 and -7.776, respectively. The G series outperformed the S series in scores. ADME analysis confirmed all compounds adhered to Lipinski's rule of five. In addition, IR and NMR provided details about the structure of the compounds. Antimicrobial activity was assessed against Escherichia coli, Staphylococcus aureus, and Candida albicans, with compounds G2 and S2 showing exceptional minimum inhibitory concentration (MIC) values of 6.25 μg/mL against E. coli. S2 also demonstrated impressive activity against S. aureus (MIC 3.12 μg/mL), and S4 exhibited potent activity against C. albicans (MIC 0.8 μg/mL) than fluconazole (1.6 μg/mL). Additionally, antihelmintic activity was evaluated, with G1, G3, G8, S2, S4, S7, and S8 showing effective paralysis and death time 20 min and below at 50 mg/mL concentration. These results underscore the potential of new imidazolidine-4-one derivatives as suitable sources to develop a drug candidate to treat resistant infections.
Neurodegenerative disorders (NDs) such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and amyotrophic lateral sclerosis are severe and life-threatening conditions in which significant damage of functional neurons occurs to produce psycho-motor malfunctions. NDs are an important cause of death in the elderly population worldwide. These disorders are commonly associated with the progression of age, oxidative stress, and environmental pollutants, which are the major etiological factors. Abnormal aggregation of specific proteins such as α-synuclein, amyloid-β, huntingtin, and tau, and accumulation of the associated oligomers in neurons are the hallmark pathological features of NDs. Existing therapeutic options for NDs are only symptomatic relief and do not address root-causing factors, such as protein aggregation, oxidative stress, and neuroinflammation. Cannabidiol (CBD) is a non-psychotic natural cannabinoid obtained from Cannabis sativa that possesses multiple pharmacological actions, including antioxidant, anti-inflammatory, and neuroprotective effects in various NDs and other neurological disorders both in vitro and in vivo. CBD has gained attention as a promising drug candidate for the management of neurodegenerative disorders, such as Alzheimer's disease and Parkinson's disease, by inhibiting protein aggregation, free radicals, and neuroinflammation. In parallel, CBD has shown positive results in other neurological disorders, such as epilepsy, depression, schizophrenia, and anxiety, as well as adjuvant treatment with existing standard therapeutic agents. Hence, the present review focuses on exploring the possible molecular mechanisms in controlling various neurological disorders as well as the clinical applications of CBD in NDs including epilepsy, depression and anxiety. In this way, the current review will serve as a standalone reference for the researchers working in this area.