Depression, a common mental disorder, is one of the major contributors to the overall global burden with more than 264 million individuals affected worldwide. Monoamine oxidase inhibitors (MAOIs) have well-known efficacy for treating depression and other related disorders. Herein we report the implementation of extensive in-silico calculations to predict the mono-amine inhibitory potential of an in-house library of piperazine-based compounds. In this connection, a multistep virtual screening protocol based on pharmacophore modeling, molecular docking and Quantitative Structure-Activity Relationship (QSAR) was carried out by MOE. Further, to assess its ability to cross the blood brain barrier, ADME properties of the compounds were predicted. Compounds predicted the highest enzyme inhibition by QSAR was synthesized for experimental validation. Both the synthesized compounds (I15 and I21) presented good strength against Monoamine Oxidase in in vitro enzyme inhibitory activity.
Acetylcholine esterase (AChE) is a key biological target responsible for the management of cholinergic transmission, and its inhibitors are used for the therapy of Alzheimer's disease. In the present study, a small library of molecules with 1,3-di-4-piperidylpropane nucleus were docked on AChE. The selected compounds were synthesized and evaluated for their enzyme inhibition. P25 and P17 expressed significantly higher AChE inhibition than standards with IC50 values of 0.591μM and 0.625μM, respectively. Binding mode of derivatives in the active site of AChE revealed dual binding of molecules in peripheral anionic site (PAS) and catalytic anionic site (CAS) of enzyme cavity.
Depression, a common mental disorder, is one of the major contributors to the overall global burden with more than 264 million individuals affected worldwide. Monoamine oxidase inhibitors (MAOIs) have well-known efficacy for treating depression and other related disorders. Herein we report the implementation of extensive in-silico calculations to predict the mono-amine inhibitory potential of an in-house library of piperazine-based compounds. In this connection, a multistep virtual screening protocol based on pharmacophore modeling, molecular docking and Quantitative Structure-Activity Relationship (QSAR) was carried out by MOE. Further, to assess its ability to cross the blood brain barrier, ADME properties of the compounds were predicted. Compounds predicted the highest enzyme inhibition by QSAR was synthesized for experimental validation. Both the synthesized compounds (I15 and I21) presented good strength against Monoamine Oxidase in in vitro enzyme inhibitory activity.
Objective: The present study was designed to assess the perception, need and the barriers of PV and ADRs reporting in the hospital settings of Karachi, Pakistan.
Methods: A cross-sectional survey was conducted from October 2019 to February 2020 by the random sampling in the healthcare professionals including physicians, pharmacists and nurses. Questionnaire was distributed to 525 participants (n=175 from each group) being serving for one or more year in hospitals and clinics. Overall, 425 participants were responded having 138 physicians, 143 pharmacists and 145 nurses.
Results: Perception of pharmacovigilance was found to be 81.02%, 73.40% and 35.17% respectively in physicians, pharmacists and nurses. Overall, 80.70% of respondents were felt the need of drug monitoring system in each hospital to improve patients’ responses against treatment. The main hindrance for PV in our society was the lacking/ absence of the ADRs monitoring and reporting system marked by the physicians and pharmacists.
Conclusion: ADRs reporting and pharmacovigilance are not practiced properly in our region. It’s a time to pay attention to this neglected area not only to strengthen the infra structure of healthcare units but also to increase the patient compliance and to avoid any drug associated disaster in future.
Clinical pharmacy services are the specialized practices of pharmacists to provide pharmaceutical care. All these activities are documented as pharmacist interventions to avoid medication errors which occur during prescribing, dispensing, and administration. The purpose of this study is to conduct an economic analysis of the pharmacist interventions using integrated health system.
In present study, some 4-piperidinopiperidine (PP) and 4-amino methylpiperidine (AMP) derivatives (PP1-3 and AMP4-9) have been synthesized to explore their analgesic potential. Activity of compounds evaluated by in-vivo thermal (tail immersion) method produced significant analgesia at different doses. Docking results explained good binding affinity of synthesized derivatives and potential interaction of all compounds with mu-opioid receptor. The pharmacophoric model of synthesized compounds showed possible structural features required for analgesic activity when compared with standards (Fentanyl, Morphine, Pethidine). Among all PP1, AMP5 and AMP6 emerged out as potent analgesic agents.
Graphical abstract
Extensive research has been dedicated to develop compounds that can target multiple aspects of Alzheimer's disease (AD) treatment due to a growing understanding of AD's complex multifaceted nature and various interconnected pathological pathways. In the present study, a series of biological assays were performed to evaluate the potential of the tryptamine analogues synthesized earlier in our lab as multi-target-directed ligands (MTDLs) for AD. To assess the inhibitory effects of the compounds, various in vitro assays were employed. Three compounds,
The present study envisioned some antioxidant candidates having 1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole (TRY), 3-(2-bromoethyl)indole (BEI) and 7-azindole (AI) nucleus. Derivatives of these indole molecules were synthesized and their scavenging activity for reactive oxygen species (ROS) investigated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. T3, T42 exhibited significant radical scavenging potential which is comparable to ascorbic acid (standard), while T36 appeared as most potent antioxidant by displaying better scavenging activity than standard molecule. Molecular docking study revealed good binding score and interactions of T36 with target human antioxidant enzyme (PDB code: 3MNG) validating the results of biological activity.
In the present study, some 9-aminoacridine derivatives have been synthesized by condensation of 9-aminoacridine with substituted phenacyl, benzoyl, and benzyl halides (RM1-RM6). Compounds were investigated for acetylcholinesterase and butyrylcholinesterase inhibition potential, considering these enzymes playing a key role in Alzheimer’s disease. All derivatives showed better inhibition of enzymes than the standard galantamine, whereas except RM4, all exhibit better results than tacrine, a well-known acridine derivative used for the treatment of Alzheimer’s disease.
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