BACKGROUND In this study, we focused primarily on three anti-malarial drugs that were tested against two malarial targets. Anti-malarial drugs like chloroquine, mefloquine, proguanil were chosen, while DHFR and GST targets from human malaria parasites such as Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax were considered for the study. OBJECTIVE The purpose of this study was to determine the sequence and structural similarity of proteins DHFR and GST among four Plasmodium species as well as to discover in silico interactions with aforementioned drug candidates. METHODS To conduct research, many bioinformatics databases like PDB, UniProt, DrugBank, PubChem; tools, and software's like Phyre 2.0, Clustal O (1.2.4), and AutoDock 4, AutoDock vina, Discovery studio visualizer were used to determine the evolutionary significance of Plasmodium species. RESULT Hence that variation has shown a difference in the binding patterns of drugs with target proteins. Our findings revealed Plasmodium spp divergence or convergence as well as how structurally and sequentially they share similar or dissimilar features. CONCLUSION As a result of the diversity, variations in protein-drug binding patterns have emerged.
BACKGROUND:Identification of clinical drug-drug interaction (DDI) risk is an important aspect of drug discovery and development owing to poly-pharmacy in present-day clinical therapy. Drug metabolizing enzymes (DME) plays important role in the efficacy and safety of drug candidates. Hence evaluation of a New Chemical Entity (NCE) as a victim or perpetrator is very crucial for DDI risk mitigation. ZY12201 (2-((2-(4-(1H-imidazol-1-yl) phenoxy) ethyl) thio)-5-(2-(3, 4- dimethoxy phenyl) propane-2-yl)-1-(4-fluorophenyl)-1H-imidazole) is a novel and potent Takeda-G-protein-receptor-5 (TGR-5) agonist. ZY12201 was evaluated in-vitro to investigate the DDI liabilities.OBJECTIVE:The key objective was to evaluate the CYP inhibition potential of ZY12201 for an opportunity to use it as a tool compound for pan CYP inhibition activities.METHOD:In-vitro drug metabolizing enzymes (DME) inhibition potential of ZY12201 was evaluated against major CYP isoforms (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4/5), aldehyde oxidase (AO), monoamine oxidase (MAO), and flavin-containing monooxygenase (FMO in human liver cytosol/mitochondrial preparation/ microsomes using probe substrates and Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) method.RESULTS:The study conducted on ZY12201 at 100 µM ZY12201 was found to reduce the metabolism of vanillin (AO probe substrate), tryptamine (MAO probe substrate), and benzydamine (FMO probe substrate) by 49.2%, 14.7%, and 34.9%, respectively. ZY12201 Ki values were 0.38, 0.25, 0.07, 0.01, 0.06, 0.02, 7.13, 0.03 and 0.003 μM for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5 (substrate: testosterone) and CYP3A4/5 (substrate: midazolam), respectively. Time-dependant CYP inhibition potential of ZY12201 was assessed against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4/5 and no apparent IC50 shift was observed.CONCLUSIONS:ZY12201, at 100 µM concentration showed low inhibition potential of AO, MAO, and FMO. ZY12201 was found as a potent inhibitor of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4/5 while moderately inhibits to CYP2E1. Inhibition of CYP1A2, CYP2B6, CYP2C19, and CYP2E1 by ZY12201 was competitive, while inhibition of CYP2C8, CYP2C9, CYP2D6, and CYP3A4/5 was of mixed-mode. ZY12201 is a non-time-dependent inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4/5. In summary, the reported Ki values unequivocally support that ZY12201 has a high potential to inhibit all major CYP isoforms. ZY12201 can be effectively used as a tool compound for in-vitro evaluation of CYP-based metabolic contribution to total drug clearance in the lead optimization stage of Drug Discovery Research.
BACKGROUND:Neurological complications are most likely to be fatal and cause loss of ability to function or care for self. These include Alzheimer's disease and cognitive impairment. The main aim of the review is to determine the effects of various drugs and their cognitive risk with the need to opt for herbal therapy as an adjuvant in treating neurological conditions like Alzheimer's disease with lesser-known side effects. The Methodology: Involved a detailed literature survey which was performed through an online database, such as Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study included randomized trials and original research conducted by herbal supplements on animal models to assess expression of upregulation of signalling pathways. Various studies involved in treating dementia, neurological disorders, Alzheimer disease, cognitive dysfunction were included.RESULTS:Found that various studies involved plant-based products were showing improvement in prevention of disease and signalling pathways with lesser-known side effects.CONCLUSION:It was observed that plant-based products play a major role in the prevention of neurological complications. Herbal medicines could most suitably prevent Alzheimer's risk with less known side effects in contrast with the existing treatment patterns. However, to improve the utility of herbal medicines, more evidences from in vitro, in vivo, and clinical trials need to be addressed.
The use of pharmacotherapy for improving healthcare in society is increasing. A vast majority of patients have either received subtherapeutic treatment (which could result from low pharmacokinetic) or experienced adverse effects due to the toxic levels of the drug. The medicines used to treat chronic conditions, such as epilepsy; cardiovascular diseases; and oncological, neurological, and psychiatric disorders, require routine monitoring. New targeted therapies suggest an individualized treatment that can slowly move practitioners away from the concept of a one-size-fits-all-fixed-dosing approach. Therapeutic drug use can be monitored based on pharmacokinetic, pharmacodynamic, and pharmacometric methods. Based on the experiences of therapeutic drug monitoring of various agents across the globe, we can look ahead to the possible developments of therapeutic drug monitoring in India.
BACKGROUND:Herbal products are derived from different natural sources, mainly used as a source of food material and medicine in the health sectors since ancient times. Herbal products have gained popularity in modern medicine due to their beneficial health properties and pharmacological activities. Flavonoids are an important class of secondary metabolites found to be present in medicinal plants and their derived products. Flavonoids have been known for their anti-allergic, anti-bacterial, anti-diabetic, anti-inflammatory, anti-viral, anti-proliferative, anti-mutagenic, antithrombotic, anti-carcinogenic, anti-oxidant and hepatoprotective activities in the medicine. Nicotiflorin is a flavonoidal class phytochemical, found in medicinal plants, including Traditional Chinese medicine.METHODS:Scientific data on the medicinal importance and pharmacological activities of nicotiflorin have been collected and analyzed in the present work in order to know the therapeutic importance of nicotiflorin in medicine. Scientific data have been collected from Google, Google Scholar, Science Direct, PubMed and Scopus and analyzed in the present work. Analytical techniques data of separation, isolation and identification of nicotiflorin have also been collected and presented in the current work. Further biological importance of flavonoidal class phytochemicals was also discussed in the present work to understand the biological importance of nicotiflorin in medicine as it belongs to the flavonoid class.RESULTS:Scientific data analysis revealed the therapeutic importance and pharmacological activities of nicotiflorin. Nicotiflorin has significant biological potential against coronavirus, ischemia, renal impairment, hepatic complication, memory dysfunction and myocardial infarction. The biological potential of nicotiflorin against α-glucosidase and α-amylase enzymes, multiple myeloma cells and insulin secretion has also been discussed in the present work. Analytical data revealed the significance of modern analytical tools in medicine for the isolation, separation and quantification of nicotiflorin.CONCLUSION:Scientific data analysis of different research works revealed the biological importance and therapeutic potential of nicotiflorin in medicine.
