Current drug discovery technologies最新文献

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.

Background: Our research highlights the synthesis of newer antimalarial compounds using molecular modeling studies.

Objective: The study investigates a series of isocryptolepine derivatives from previous literature, focusing on their biological activities as antimalarial agents.

Methods: Computational methods such as molecular docking and QSAR were employed to gain insights into the interaction between the synthesized compounds and the target enzyme PfDHFR-TS.

Results: Molecular docking studies helped to identify key binding interactions, supporting the design of more effective compounds. Using CoMFA and CoMSIA, the study explored steric, electrostatic, and hydrogen-bonding fields, providing a quantitative structure-activity relationship (QSAR) for 49 compounds.

Conclusion: The CoMFA model yielded strong predictive r² values of 0.971, while the CoMSIA model highlighted the significance of hydrophobic and hydrogen bond interactions. These findings inform the design of novel isocryptolepine derivatives with improved antimalarial activity.

Berberine is an isoquinoline alkaloid with strong pharmacological activity such as analgesic, antioxidant, neuroprotective, antivirus, anti-inflammatory, anti-seizure, anti-obesity, and hypolipidemic effects. Accumulated evidence indicates berberine plays an inhibitory role against infection of numerous viruses, including human immunodeficiency virus, respiratory syncytial virus, hepatitis C virus, human papillomavirus, human cytomegalovirus, and influenza virus. Berberine's antiviral action has shown promise, making it a viable option for synergistically enhancing the inhibitory effect of current antiviral medicines. This review provides an overview of prior berberine antiviral studies to prepare for its potential use as a natural antiviral agent in future research.

Background: Atorvastatin (ATO) is an HMG-CoA reductase inhibitor used to lower blood cholesterol, but it causes renal injury in high doses. Thymoquinone (TQ), is a natural antioxidant that has been shown to protect the kidney through its anti-inflammatory, antioxidant, & antiapoptotic, effects.

Objective: The current study aimed to investigate whether posttreatment TQ could reverse ATOinduced renal injury, and the possible mechanism of action by which TQ produced such an effect.

Methods: Forty adult male rats were divided into 4 groups: (control; TQ-treated; ATO-treated; ATO plus TQ-treated). Blood and kidney tissue samples were tested for kidney functions, oxidative stress and apoptosis markers, and morphometric analyses of the histopathological and ultrastructural evaluations. Statistical analyses were done using JASP, Shapiro-Wilk, and Levene's test. ANOVA and Kruskal-Wallis tests were done to determine differences between groups. The significance level was set at p<.05.

Results: The ATO-treated group showed abnormal outcome measures including kidney functions, oxidative stress and apoptotic markers, and morphometric analyses of the histopathological and ultrastructural findings. Post-treatment TQ improved all outcome measures.

Conclusion: Posttreatment TQ could reverse oxidative stress-induced renal injury produced by highdose ATO, suggesting a potential clinical application in patients with renal insufficiency with hypercholesterolemia.

Still today, peptic ulcer disease (PUD) is a major digestive illness that affects millions of people around the world every year. This study looks at both traditional and herbal ways of treating PUD, focusing on how they work, how well they work, and whether they can work together. Pharmaceuticals like antibiotics, proton pump inhibitors (PPIs), and H2-receptor antagonists are common ways to treat the condition. In more serious cases, surgery may also be an option. The use of medical plants in phytotherapy, an herbal treatment, has shown promise in helping people with PUD deal with their symptoms and speed up the healing of ulcers. Citrus maxima (Pomelo), a plant in the Rutaceae family, may be able to help treat PUD because it has functional and antioxidant properties. In addition, studies on how well different plants treat PUD have shown that they have anti-inflammatory and cytoprotective qualities. Also, the parts of photosynthesis that plants use contain many beneficial substances that might help with the treatment of PUD. This all-around method would deal with many pathogenic pathways at the same time. More study needs to be done to learn more about how herbal therapies can be used to treat PUD and how they can be combined with other common treatments.

Background: Diabetic wound healing poses a significant challenge due to the intricate disruptions in cellular and molecular processes induced by hyperglycaemia, leading to delayed or impaired tissue repair. Computational techniques offer a promising avenue for unravelling the complexities of diabetic wound healing by elucidating the molecular mechanisms involved.

Methodology: This study utilized in silico molecular docking and dynamics simulations to explore the potential therapeutic effectiveness of olivetol, a phenolic compound, in the context of diabetic wound healing. Furthermore, computational methodologies, encompassing pkCSM, Swiss ADME, OSIRIS® property explorer, PASS online web resource, and MOLINSPIRATION® software, were employed to forecast the pharmacokinetic properties, biological actions, and in vitro analyses, such as MTT and scratch assays, to evaluate the therapeutic effectiveness of olivetol in wound healing.

Results and discussion: Our findings have revealed olivetol to be a promising candidate for targeting multiple pathways implicated in diabetic wound healing. Its ability to modulate inflammation, oxidative stress, extracellular matrix remodeling, angiogenesis, and cell signaling suggests a multifaceted approach to promoting effective wound repair. Moreover, olivetol has been found to demonstrate strong binding affinity with key MRSA target proteins, indicating its potential as an antimicrobial agent against MRSA infections in diabetic wounds. The in vitro MTT assay demonstrated cell viability with an IC₅₀ value of 40.80 μM, highlighting its cytotoxicity potential. Additionally, the scratch assay confirmed promising wound healing activity, showcasing its effectiveness in promoting cell migration and closure.

Conclusion: Olivetol emerges as a promising candidate for targeted interventions in non-healing diabetic wounds, particularly due to its ability to address prolonged inflammation, a common obstacle in diabetic wound healing.