Current drug discovery technologies最新文献

Introduction: The root bark of Berberis aristata has been utilized by indigenous peoples for wound treatment for centuries. The mature root barks are crushed into a paste and applied to the wound's surface.

Objective: The focus of this research is to analyse the wound healing activities of an ethanolic extract of Berberis aristata, as well as to use molecular docking to establish the likely mechanism of the potent phytochemical. There is no scientific evidence to support the usage of root bark extract of Berberis aristata.

Methods: The Herbal ointment, which comprises (1%, 2%, and 4% w/w) ethanolic extract of root bark, was developed to test the wound healing ability of incision and excision wounds, and the molecular mechanism was established using Auto-Dock software.

Results: Epithelization stage, wound index, % wound contraction area, hydroxyproline content, DNA estimate, and histopathological assessments were performed on the incision wound model. Tensile strength was assessed in an excision wound model. TLC was used to identify the samples after successive extractions with different solvents based on polarity.

Conclusion: Berberine and tetrahydropalmatine were major active phytoconstituent found in root barks of Berberis aristata as secondary metabolites. Animals treated with 4% w/w formulation demonstrated considerable wound contraction, epithelization time, and wound index in the excision model. In contrast, to control and standardize the concentrations of hydroxyproline, total amino acids, and DNA in recovering tissue were higher. At 4% w/w extract formulation, the parameters studied indicated a substantial result. Berberine and tetrahydropalmatine, active metabolites which are present in the ethanolic extract of Berberis aristata, were found to be responsible for wound healing. Based on ligand interactions, the findings verified Berberis aristata ethnomedicinal claim in a wound healing capacity.

Introduction: Diabetes is the most common component of metabolic syndrome, including abdominal obesity, insulin resistance, hypertension, and dyslipoproteinemia.

Objective: This study aims to determine whether vanillic acid has antihyperlipidemic properties in diabetic hypertensive rats.

Methods: For this study healthy male albino Wister rats (180-220 gm) were selected. A 20-week highfat diet (HFD) was given to produce diabetic hypertension in Wister rats. Control and diabetic hypertensive rats were treated with vanillic acid. Vanillic acid effects on lipid profiles (cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoproteins (HDL)) and lipid metabolizing enzymes LPL, LCAT, and HMG CoA reductase studied by a conventional method. To understand the effect of vanillic acid control, experimental rat lipid and metabolic enzymes were studied and treated and controlled animal liver tissues were observed using the different histology staining agents.

Results: Vanillic acid caused considerable lipid profile reductions except for HDL and increased plasma HDL levels. After eight weeks of vanillic acid administration also boosts lipid marker enzyme activity (HMG CoA reductase, LPL, and LCAT). In addition, vanillic acid reduces the accumulation of collagen in liver tissues.

Conclusion: These research studies suggest that vanillic acid has antihyperlipidemic effects in diabetic hypertensive rats fed an HFD.

Small Angle Neutron Scattering (SANS) is a powerful and novel tool for the study of soft condensed matter, including the microscopic and nanomaterials used for drug discovery and delivery. The sample is exposed to a neutron beam, and neutron scattering occurs, which is studied as a function of the scattering angle to deduce a variety of information about the dynamics and structure of the material. The technique is becoming very popular in biomedical research to investigate the various aspects of structural biology. The low-resolution information on large heterogeneous, solubilized biomacromolecular complexes in solution is obtained with the use of deuterium labelling and solvent contrast variation. The article reviews the basics of the SANS technique, its applications in drug delivery research, and its current status in biomedical research. The article covers and overviews the precise characterization of biological structures (membranes, vesicles, proteins in solution), mesoporous structures, colloids, and surfactants, as well as cyclodextrin complexes, lipid complexes, polymeric nanoparticles, etc., with the help of neutron scattering. SANS is continuously evolving as a medium for exploring the complex world of biomolecules, providing information regarding the structure, composition, and arrangement of various constituents. With improving modelling software automation in data reduction and the development of new neutron research facilities, SANS can be expected to remain mainstream for biomedical research.

Background: Tuberculosis (TB) is one of the leading causes of death in the post-COVID- 19 era. It has been observed that there is a devastating condition with a 25-30% increase in TB patients. DNA gyrase B isoform has proved its high potential to be a therapeutically effective target for developing newer and safer anti-TB agents.

Objective: This study aims to identify minimum structural requirements for the optimization of thiazolopyridine derivatives having DNA gyrase inhibitory activities. Moreover, developed QSAR models could be used to design new thiazolopyridine derivatives and predict their DNA gyrase B inhibitory activity before synthesis.

Methods: 3D-QSAR and Group-based QSAR (G-QSAR) methodologies were adopted to develop accurate, reliable, and predictive QSAR models. Statistical methods such as kNN-MFA SW-FB and MLR SW-FB were used to correlate dependent parameters with descriptors. Both models were thoroughly validated for internal and external predictive abilities.

Results: The 3D-QSAR model significantly correlated steric and electrostatic descriptors with q² 0.7491 and predicted r² 0.7792. The G-QSAR model showed that parameters such as SsOHE-index, slogP, ChiV5chain, and T_C_C_3 were crucial for optimizing thiazolopyridine derivatives as DNA gyrase inhibitors. The 3D-QSAR model was interpreted extensively with respect to 3D field points, and the pattern of fragmentation was studied in the G-QSAR model.

Conclusion: The 3D-QSAR and G-QSAR models were found to be highly predictive. These models could be useful for designing potent DNA gyrase B inhibitors before their synthesis.

Background: Flavanone compounds and their related derivatives are reported in controlling cell cycle, angiogenesis, and metastasis. Phosphoinositide 3-kinases is a major drug target.

Methods: Crystalize structure of Phosphoinositide 3-kinases-Akt complex obtained from Protein Data Bank (PDBID: 3CQW) was selected as receptor protein and the binding site has been identified with PDBSum Database. Flavanone and its derivatives were retrieved using freely available existing drug databases like Drug Bank, Zinc, and PubChem. New derivatives were modified by altering the flavanone at Beta ring position. This modification would help in maintaining stable structural conformation and retaining better anticancer activity. Retrieved Flavanone derivatives from the drug database were docked against 3CQW Protein with the advanced docking tool FlexX. MD simulations of the best molecule were performed with the Desmond package by calculating nonbonding interactions such as electrostatic interaction and hydrogen bond stable and favorable conformations were calculated.

Results: These interaction studies would help identify new potential drug candidates with the help of computer-aided drug designing techniques.

Conclusion: Natural chemicals have received a lot of attention because of their vast range of applications in human health and disease prevention without creating any negative side effects. Molecular docking is an essential approach for drug development since it allows for effective screening of potential therapeutics in a short time. We hypothesized in this paper that natural flavanone and its derivatives may be effective as Akt-1 inhibitors.

COVID-19, aka Coronavirus Disease 2019, triggered by new severe acute respiratory syndrome coronavirus-2 or SARS-CoV-2, is now a public health emergency due to its rapid spread, high transmission efficiency, and severe viral pandemic that is significantly increasing the number of patients and associated deaths. Currently, no specific treatment is available for this highly contagious virus. The unavailability of effective and specific treatments and the severity of this epidemic situation potentiate medicinal chemists' in supporting new prophylactic or therapeutic interventions against COVID-19. This study discusses the therapeutic potential of hesperidin, a traditionally used herbal medicine with an exceptional safety profile. Recent studies on hesperidin advocate its promising potential in the prevention and management of COVID-19. This paper also discusses the recent clinical studies based on the previously documented antiviral activity of hesperidin. Herein, we propose the detailed preclinical and clinical manifestations of hesperidin based on its multifaceted bioactivities to develop a novel anti-COVID-19 lead.

Drug discovery and development have been sped up because of the advances in computational science. In both industry and academics, artificial intelligence (AI) has been widely used. Machine learning (ML), an important component of AI, has been used in a variety of domains, including data production and analytics. One area that stands to gain significantly from this achievement of machine learning is drug discovery. The process of bringing a new drug to market is complicated and time-consuming. Traditional drug research takes a long time, costs a lot of money, and has a high failure rate. Scientists test millions of compounds, but only a small number make it to preclinical or clinical testing. It is crucial to embrace innovation, especially automated technologies, to lessen the complexity involved in drug research and avoid the high cost and lengthy process of bringing a medicine to the market. A rapidly developing field, a branch of artificial intelligence called machine learning (ML), is being used by numerous pharmaceutical businesses. Automating repetitive data processing and analysis processes can be achieved by incorporating ML methods into the drug development process. ML techniques can be used at numerous stages of the drug discovery process. In this study, we will discuss the steps of drug discovery and methods of machine learning that can be applied in these steps, as well as give an overview of each of the research works in this field.

Background: An ulcer is a condition characterized by inflammation, irritation, or erosion in the mucosal lining of the stomach or duodenum. Hence, peptic ulcer is the ulcer of both the stomach and the duodenum. 10% of the world's population is affected by chronic peptic ulcers. The formation of peptic ulcers depends on gastric juice pH and the decrease in mucosal defenses. Nonsteroidal antiinflammatory drugs (NSAIDs) and Helicobacter pylori (H. pylori) infection are the two significant factors disrupting mucosal resistance to injury. Indian herbal plants are exceptional for their ethnic, ethnobotanical, and ethno-pharmaceutical use. In this review, attempts have been made to gain information regarding some plants that may be used to treat or prevent peptic ulcers. The ultimate goal of peptic ulcer disease treatment is to reduce pain, cure ulcers, and prevent recurrence.

Objective: The aim of the study was to gain knowledge about several common medicinal plants employed in Ayurveda or contemporary science for the treatment or prevention of peptic ulcers and some natural and simple approaches to cure ulcers using readily available herbs.

Methods: The literature search was carried out using search engines, like Google Scholar, Scopus, PubMed, Medline, Springer, etc. Results: The extensive literature search showed natural herbs to have potential anti-ulcer activity, including cabbage, bananas, liquorice, fenugreek, garlic, Terminalia chebula, Acacia arabica, Aegle marmelos, Aloe vera, Allium sativum, Plantago ispagula, Mimosa pudica, Annona squamosa, Azadirachta indica, and Galega purpurea.

Conclusion: This study concluded several medicinal plants to effectively prevent or cure peptic ulcers caused by a variety of factors, including H. pylori, aspirin, indomethacin, alcohol, and others.

Background: Parkinson's disease (PD) is a neurodegenerative syndrome defined by a variety of motor, cognitive, and psychomotor dysfunctions. The current pharmaceutical treatment focuses on treating the condition's symptoms. They are primarily concerned with reducing illness symptoms or avoiding dopamine metabolism. As our understanding of disease pathogenesis improves, new therapeutic approaches emerge.

Objective: This article aims to describe the standard Parkinson's medications based on symptoms and requirements. It emphasizes recent advancements in symptomatic therapy for motor indications and achievements in the research and clinical testing of medicines that promise to enable disease modification in patients with already-manifest PD.

Methods: Information for this paper was found by looking through Google Scholar and reading several research and review articles from Bentham Science, Science Direct, Elsevier, Frontiers, Taylor & Francis, and other publishers.

Result: Parkinson's disease therapeutic interventions are now limited to symptomatic therapy, mostly in dopaminergic medications and deep brain stimulation (DBS). They have the potential to deliver great therapeutic progress, yet they can also have serious drawbacks that decrease a patient's quality of life. The progress of pluripotent stem cell therapies and genome engineering procedures has sparked renewed hope for the treatment of a wide range of human illnesses, particularly genetic abnormalities.

Conclusion: The current Parkinson's therapy trends are successful and continually evolving, with several drugs currently undergoing clinical trials. As these new therapies constantly coming out and can be used together, they will likely change how Parkinson's disease is treated in the coming years.