Current drug discovery technologies最新文献

Background: Type II diabetes mellitus is treated as one of the detrimental diseases and the drugs used for its treatment often lead to several side effects. Therefore, herbal medication of plant origin with lesser offshoot is a significant concern. Petroselinum crispum is a plant of pharma-ceutical interest. The present work aims to explore the potentiality assessment of flavonoids of Pe-troselinum crispum as an α-amylase inhibitor.

Methods: Compounds were extracted from the database and evaluated through drug likeliness prop-erties, ADMET and toxicity assessment. Molecular docking was done to identify the best ligand, and the dynamics simulation study was performed with the leading ligand-protein complex.

Results: Amongst the 15 bioactive compounds, apigenin appeared as the best ligand among all the studied compounds. Moreover, drug likeliness, physiochemical characteristics, and ADMET anal-yses revealed that apigenin does not deviate from Lipiniski's rule of five. Non-toxic apigenin showed a satisfactory docking score of -9.5 kcal/mol with human pancreatic α-amylase compared to the ref-erence molecule acarbose. Apigenin- α-amylase complex and apoprotein were subjected to 100ns molecular dynamics simulation to analyze the stability of the docked protein-ligand complex. The values of RMSD, RMSF, Rg, SASA and hydrogen bonding of the screened complexes showed high stability and less fluctuations of the apigenin- α-amylase complex.

Conclusion: This finding suggests apigenin as alternative therapeutics in treating diabetes mellitus by targeting the enzyme α-amylase which can be used for in vitro cross-validation studies. This study is the first documentation of the antidiabetic potentiality of the flavonoid compounds of Petroselinum crispum through in silico investigation.

Scopoletin, a naturally occurring coumarin derivative, has garnered significant attention for its diverse pharmacological properties, including potent anticancer activity. This review provides a comprehensive examination of scopoletin's anticancer effects across a wide range of tumor cell lines. The paper explores its modulation of apoptotic pathways, inhibition concentration (IC50) of cancer cell proliferation, and suppression of metastasis and angiogenesis. Additionally, the review discusses the role of scopoletin in regulating oxidative stress, inflammation, and cell cycle arrest in cancer cells. A detailed analysis of in vitro and in vivo studies highlights its efficacy, specificity, and potential for synergistic effects when used in combination with conventional chemotherapeutics. Hence, this comprehensive review aims to provide a foundation for future research and development of scopoletin as a promising anticancer agent.

The temperate, subtropical climates of Odisha state, India, provide significant benefits that can help it become a potent producer of many species of edible mushrooms. The importance of mush-rooms in diets has gained more attention in recent years due to their nutritional benefits. We aimed to update and discuss the current research information on nutritional components, including carbo-hydrates (β-glucans, trehalose, glucose), dietary fiber, proteins (ostreatin), amino acids (valine, glu-tamine, glutamic acid, aspartic acid, and arginine, lipids, vitamins (thiamine, riboflavin, pyridoxine, pantothenic acid, niacin, folic acid, nicotinic acid, and cobalamin), minerals (K, P, Na, Ca, Mg), flavor and taste contents of Odisha cultivated edible mushrooms. Additionally, their biological appli-cation in terms of antimicrobial action, antitumor, anti-inflammatory, anti-diabetic, cardioprotective properties, and antioxidant properties with mechanism of action are highlighted. Besides, we men-tioned the limitations and prospects of mushrooms.

Since the authors are not responding to the editor’s requests to fulfil the editorial requirement, therefore, the article has been withdrawn from the journal “Current Drug Discovery Technologies”

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php.

Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

An imbalance between Reactive Oxygen Species (ROS) and antioxidants in the circulatory system leads to oxidative stress, which has been linked to several pathological conditions, including cancer, aging, and neurological and cardiovascular diseases. Antioxidants play a crucial role in re-ducing oxidative damage by neutralizing harmful free radicals and preventing cellular injury. The processes generating cellular oxidative stress and the curative effects of antioxidants, the origins and effects of reactive oxygen species (ROS), the role that oxidative stress plays in the pathogenesis of disease, and the several kinds of antioxidants-including enzymatic and non-enzymatic antioxidants are thoroughly explored in this review. We also emphasized the medicinal uses of antioxidants, both natural and synthetic, in the prevention and treatment of disorders associated with oxidative stress. Furthermore, we discussed the challenges and potential paths ahead for antioxidant research, such as developing new antioxidant molecules with higher efficacy and improving antioxidant delivery sys-tems. This study provides information regarding the complicated dynamics of oxidative stress and the potential benefits of antioxidants for preserving cellular homeostasis and advancing human health.

Non-coding RNA (ncRNA) has been recognized to be an essential regulator of cellular processes and gene expression in cancer. The present study covers the various roles of ncRNAs, including circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miR-NAs), that affect cancer properties. Oncogenesis, metastasis, and treatment resistance are all pro-cesses involving ncRNAs, which have tremendous potential as new therapeutic agents and tar-gets. The review covers the broad spectrum of ncRNAs in cancer biology, including their types and activities, epigenetic control, function in metastasis and angiogenesis, detection and profiling ap-proaches, potential as biomarkers, and therapeutic possibilities. Recent advancements in next-gener-ation sequencing and other molecular methods have helped us better understand how ncRNAs work and their potential therapeutic uses. However, there are still challenges to standardizing detection technologies and producing effective RNA-based therapeutics. Therefore, further studies are needed to solve important issues in this sector. Standardization efforts are also essential to developing iden-tical methods for ncRNA collection, quantification, and analysis throughout multiple laboratories and ensuring the findings are reliable and comparable. Large-scale, multi-recentre studies are required to verify the diagnostic usefulness of ncRNA biomarkers across a wide range of patient groups. Also, more detailed mechanistic knowledge is necessary for understanding the particular molecular mech-anisms by which ncRNAs affect cancer growth, metastasis, and treatment response. This review high-lights the complex relationships between ncRNAs and cancer biology and also focuses on their po-tential effect on cancer diagnosis and treatment. It also highlights the necessity for more studies to fully understand the therapeutic potential of ncRNAs in cancer. As studies advance, using ncRNA results in clinical practice might change cancer treatment by novel opportunities for specific therapy and personalized medicine.

Objective: This study investigated the antimicrobial properties of the thanatin peptide against oral bacteria associated with dental caries and endodontic failures. Additionally, the cytotoxic effects of this peptide on human gingival fibroblast cells (HGFCs) were assessed.

Methods and materials: The antimicrobial property of thanatin was tested on Streptococcus mutans, Streptococcus salivarius, Streptococcus oralis, and Enterococcus faecalis, using the microbroth dilu-tion method. The 0.2% Chlorhexidine mouthwash was used as the control group. Additionally, the cytotoxicity was measured using the MTT assay. The results were presented descriptively and ana-lyzed via one-way ANOVA and Tukey's HSD tests.

Results: Thanatin demonstrated the strongest bacteriostatic effect (MIC) against S. salivarius, meas-uring 4.68 μg/ml, which is approximately double that of S. mutans and S. oralis, with concentrations of 9.37 and 8.75 μg/ml, respectively. The highest bactericidal activity (MBC) of thanatin was noted in S. salivarius and S. oralis at 9.37 μg/ml. The antibacterial effects of thanatin against evaluated bacteria were several times lower than those of Chlorhexidine. The cytotoxicity assessment indicated that over 70% and 60% of the HGFCs remained viable after 24 and 48 hours, respectively.

Conclusion: Although thanatin exhibited significantly higher biocompatibility, its antimicrobial ef-fectiveness against the tested oral bacteria was inferior to that of 0.2% Chlorhexidine.

Introduction: Antimicrobial resistance (AMR), according to the World Health Organi-zation, is one of the most serious risks to global public health and development. It is a serious health hazard, with over 10 million deaths expected by 2050. New treatment materials and ways to remove AMR pathogens are in great demand to combat illnesses caused by such bacteria. Hence, the current work focused on virtual screening of the therapeutic potential of new oxindole derivatives against the targeted enzymes for antibacterial activity.

Materials and methods: A series of 120 novel 3-substituted-2-oxindole derivatives were designed based on the literature and SAR study, which were screened for their binding affinity against tar-geted enzymes, such as methionyl-tRNA synthetase (1PFV) and tyrosyl-tRNA synthetase (1JIL) using AutoDock Vina software. Compounds with significant binding energy were identified and filtered for appropriate ADME properties using the SwissADME program. Furthermore, the top fifteen hit compounds were evaluated for toxicity risk and drug score with the pkCSM online tool and OSIRIS Property Explorer, respectively.

Results and discussion: The docking analysis of the top two hits revealed that compounds 4 and 6 had a binding affinity of -10.1 Kcal/mol and -10.0 Kcal/mol against the targeted enzymes, respec-tively, compared to the standard (Tetracycline -9.3 Kcal/mol and Mupirocin -7.5 Kcal/mol).

Conclusion: Hence, the best-hit compound 4 underwent MD simulation, validating its stability and successfully satisfying all in silico parameters, necessitating further synthesis and screening for in-vitro antimicrobial activity. These novel oxindole scaffolds could thus serve as promising leads for effective antibacterial drugs.

Traditional drug discovery processes have disadvantages such as efficiency, cost, and high attrition rates. In silico methods, involving computational simulations and modelling, offer powerful solutions to bridge the gap between discovery and development. This review explores various in silico approaches, including ligand-based and structure-based drug design, virtual screening, molecular docking, and ADMET prediction. We explore their utilization throughout different phases of phar-maceutical development, spanning from target identification and lead refinement to forecasting tox-icity and pharmacokinetics. In-silico methods enable rapid lead identification and optimization, re-ducing reliance on expensive wet lab experiments. They contribute to improved drug quality by pre-dicting ADMET properties and off-target effects, ultimately accelerating development timelines and lowering costs. In silico approaches are revolutionizing drug design by providing predictive and cost-effective solutions. Incorporating them into the design process streamlines lead refinement and en-hances the likelihood of success for potential drugs, ultimately expediting the translation of innova-tive treatments to patients.

The integration of artificial intelligence (AI) in pharmaceutical sciences marks a signifi-cant milestone in the field of drug discovery and development, presenting unique prospects for crea-tivity and productivity. This review article delves into the significant impact of AI on contemporary pharmaceutical practices, highlighting its incorporation in different phases of drug discovery and personalized medicine. Our goal is to offer a thorough analysis of the current landscape of AI appli-cations in the field, outline the extent of recent progress, and explore the obstacles and potential future paths for AI technologies. Significant advancements have been made in the drug development pro-cess, resulting in cost reduction and improved drug efficacy and safety profiling. In order to fully harness its potential, the various obstacles involved in the integration of AI must be overcome. These include ensuring the quality of data, navigating through regulatory requirements, and addressing eth-ical considerations. This review provides a comprehensive analysis of AI techniques, discussing the strengths and limitations of current technologies and identifying emerging trends that could poten-tially shape future pharmaceutical landscapes. Exploring the far-reaching effects of AI on healthcare, economics, and ethics, this analysis offers valuable insights into the potential of AI-driven strategies to revolutionize healthcare, making it more individualized and efficient. In the end, this review seeks to provide guidance to stakeholders in understanding the intricacies of AI in pharmaceutical sciences and utilizing its potential to improve patient outcomes.