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Current Drug Discovery Technologies - Online First
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A Comprehensive Review on Immunoregulatory Effects of Phytochemicals
Available online: 02 December 2024More LessAn efficient immune system in the host body plays a crucial role in the preservation of normal biological and immune reactions and processes, as well as the intrinsic environment. This is because the immune system is responsible for fighting off foreign invaders. A healthy immune system strengthens the body's defense against infections, illnesses, and other unwelcome pathogens, thereby reducing the risk of allergic reactions and autoimmune diseases. Innate immune cells and acquired immune system components interact in a corrective fashion to produce optimal immune responses. In recent years, researchers have begun to focus on the immune system as a potential primary target of toxicity from chemical, pharmacological, and environmental exposure. Sex, age, stress, malnutrition, alcohol, genetic variability, lifestyles, environmental pollutants, and chemotherapy are just a few of the many elements that might modify the host's immunological responses. The production, amplification, attenuation, or suppression of immunological responses are all examples of immunomodulation. There are a wide variety of synthetic and traditional treatments available, and many of them cause major side effects and develop pathogenic resistance very quickly. Natural substances called phytochemicals play a crucial role in regulating the body's immune system. Risk factors for immune response changes are discussed, as is the immunomodulatory action of phytochemicals like glycosides, alkaloids, phenolic acids, flavonoids, saponins, tannins, sterols, and steroids.
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Computational Screening of Novel Nitroimidazole Candidates: Targeting Key Enzymes of Oral Anaerobes for Anti-Parasitic Potential
Authors: Touhami Lanez, Maroua Lanez, Riad Lanez, Elhafnaoui Lanez and Badia Talbi-LanezAvailable online: 05 November 2024More LessBackgroundThe study focuses on evaluating the parasitic potential of novel metronidazole analogs using computational methods. Specifically, it aims to target key enzymes of oral anaerobes, including UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA) of Fusobacterium nucleatum and DNA topoisomerase (Topo) of Prevotella intermedia.
ObjectiveThe objective is to assess the pharmacokinetic and toxicity properties of 368 novel nitroimidazole candidates through virtual screening. Additionally, the study aims to determine the binding affinity of the most promising candidates with the target proteins through molecular docking analyses.
MethodsA combinatorial library of nitroimidazole candidates was constructed, and virtual screening was performed. Molecular docking analyses were conducted to evaluate the binding affinity of selected compounds with MurA and Topo. Further investigation involved molecular dynamic simulation to assess the stability of the compounds within the active sites of MurA and Topo.
ResultsAll selected compounds exhibited activity against both MurA and Topo. Among them, Mnz11, Mnz12, and Mnz15 demonstrated the lowest binding free energies and IC50 values. Molecular dynamic simulation indicated that these three compounds remained stable within the active sites of MurA and Topo, with RMSD values consistently below 2Å. Additionally, the antibacterial potential of the most potent compound, Mnz15, was evaluated against a series of oral microbes.
ConclusionThe study concludes that the newly identified nitroimidazole candidates show promise as anti-parasitic agents, based on their activity against key enzymes of oral anaerobes and their pharmacokinetic properties evaluated through computational methods.
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Preliminary Characterization of the Vasorelaxant Effect of Thymus atlanticus (Ball) Roussine Using Optical Methods
Available online: 04 November 2024More LessBackgroundThymus atlanticus (Ball) Roussine is a Moroccan endemic thyme species that is traditionally used as an aromatic and medicinal plant. Several studies have demonstrated its pharmacological significance and therapeutic value.
ObjectiveThe current study aimed to assess the vasorelaxant effect of the aqueous extract of this species.
MethodsThe contractility of isolated rat aortas was investigated using the multi-well organ bath technique. This method was adapted and validated in our experimental conditions using epinephrine and hydralazine as vasoconstrictive and vasodilator agents, respectively. The application of 10 µM epinephrine induced a clear vasoconstriction of the aorta rings (Lumen reduction = 31.8±0.4%). However, hydralazine induced a dose-dependent relaxation with an EC50 value of 6.1±1.2 mM. For the aqueous extract of T. atlanticus, the aortic rings were precontracted with epinephrine, and then increasing concentrations (0.125-1 mg/mL) of this extract were added cumulatively.
ResultsThe results have indicated T. atlanticus extract to have a significant vasodilatory effect in a dose-dependent manner (EC50 = 0.52±0.03 mg/mL).
ConclusionThe findings provide preliminary evidence of the vasorelaxant effect of the aqueous extract of T. atlanticus using a low-cost optical approach. However, the cellular and molecular mechanisms underlying this effect have yet to be revealed.
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AI in Clinical Trials and Drug Development: Challenges and Potential and Advancements
Available online: 28 October 2024More LessArtificial intelligence (AI) is one of the fastest-growing fields in various industries, including engineering, architecture, medical and clinical research, aerospace, and others. AI, which is a combination of machine learning (ML), deep learning (DL), and human intelligence (HI), is revolutionizing drug discovery and development by making it more cost-effective and efficient. It is also being used in fields such as medicinal chemistry, molecular and cell biology, pharmacology, pharmacokinetics, formulation development, and toxicology. AI plays a crucial role in clinical testing by enhancing patient stratification, patient sample evaluation, and trial design, assisting in the identification of biomarkers, determining efficacy criteria, dose selection, trial length, and target patient population selection. The primary objective of this study is to emphasize the importance of AI in clinical trials and drug development, while also exploring the existing challenges and potential advancements in AI within the healthcare industry. A comprehensive literature review was conducted, covering the period from 1998 to 2023. The Science Direct, PubMed, and Google Scholar databases were searched for relevant information. A variety of publications, including Research Gate, Nature, MDPI, and Springer Link, provided pertinent data. This study aimed to gain a deeper understanding of the use of AI in clinical research and drug development, as well as its potential and limitations. We also discuss the benefits and main data limitations of the traditional trial and drug development approach. AI approaches are currently being used to overcome research obstacles and eliminate conceptual or methodological limitations. After discussing possible obstacles and coping mechanisms, we provide several recommendations to help individuals understand the challenges and difficulties associated with clinical research and drug development. It is essential for pharmaceutical companies to have a cutting-edge AI strategy if AI is to become a routine tool for clinical research and drug development.
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An Update on Clinically Evaluated Medicinal Plants for Psoriasis Management
Available online: 28 October 2024More LessPsoriasis is a prevalent inflammatory disease affecting almost 0.5-5% of the world population. Multiple treatment approaches have been developed to manage psoriasis so far. Although concerns exist in the long-term usage of conventional and biological agents in terms of safety, effectiveness, expensiveness, and tolerability, complementary and alternative medicine (CAM) is a promising point of view for future psoriasis management. In this study, databases including Scopus, PubMed, Google Scholar, and Web of Science were searched for relevant literature on herbal medications clinically evaluated for psoriasis, especially those originating from traditional medicine. About 40 relevant papers were selected by March 2023. Most of the studies were clinical trials on poly-herbal formulations from traditional Chinese medicine (TCM). There are controversial results regarding the efficacy of these herbal formulations in psoriasis mainly due to the variation in the study design. Moreover, the probable protective mechanisms and responsible herbal metabolites of these formulations are summarized. There is a global need for more in-vitro and in-vivo studies based on the standard protocols in terms of the evaluation of the safety and efficacy of topical/ systemic herbal preparations for psoriasis.
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In Vitro Antibacterial Activity of Adiantum capillus veneris Extraction with Methanol, Chloroform, and Ether Solvents against Methicillin-resistant Staphylococcus aureus
Authors: Mahdiyeh Ebrahimzadeh, Solmaz Rahbari, Reza Hosseini Doust and Faraz MojabAvailable online: 25 October 2024More LessBackgroundThe increasing problem of multi-drug resistant (MDR) pathogens is a worldwide concern, especially in the pharmaceutical industry. At the same time, medicinal plants have renewed interest because of their wide variety of bioactive phytochemicals, which could be used to develop new antimicrobial drugs. This renewed interest is partly due to the growing resistance to traditional drugs and their associated side effects.
MethodsThe objective of this study is to assess the antimicrobial properties of the total extract and various fractions of Adiantum capillus veneris against Methicillin-resistant Staphylococcus aureus (MRSA). The aerial parts of Adiantum capillus veneris were subjected to extraction using methanol, chloroform, and ether, and the resulting extracts were tested for their antimicrobial activity against MRSA. Additionally, essential oil was obtained from the aerial parts using a Clevenger apparatus and boiling water. Furthermore, Gas Chromatography-Mass Spectrometry (GC/MS) was utilized to analyze the phytochemicals isolated from the extracts of Adiantum capillus veneris.
ResultsThe essential oil was obtained through distillation and then analyzed using GC/MS. The antimicrobial activity was evaluated using the agar diffusion method.
ConclusionGC/MS analysis revealed that the composition was primarily phytol (59.9%), constituting 99.3% of phyto-constituents. However, both the total extract and the individual fractions exhibited no inhibitory effects against MRSA strains.
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Long Non-Coding RNA HCP5 Affects Ferroptosis in Lung Adenocarcinoma through miR-17-5p/HOXA7 Axis
Authors: Qingyun Pan, Zige Tang, Jiayu Zheng, Lingxin Yan and Quanfan ChenAvailable online: 21 October 2024More LessBackgroundFerroptosis, a regulated cell death initiated by Fe-dependent lipoperoxidation, is closely linked to the development of lung adenocarcinoma (LUAD). LncRNA human leukocyte antigen complex P5 (HCP5) has been confirmed as oncogenic in LUAD, but its function in ferroptosis is unknown.
ObjectiveBased on the previous bioinformatics mining of the ceRNA (competitive endogenous RNA) network HCP5/miR-17-5p/ Homeobox A7 (HOXA7) related to ferroptosis in LUAD, in this study, we characterized the cell-based experiments to validate the binding between the HCP5/miR-17-5p/HOXA7 axis and ferroptosis.
MethodsThe HCP5/miR-17-5p/HOXA7 linkage was identified by a two-luciferase reporter. Cell Counting Kit-8 (CCK-8) and Transwell assay were employed for the detection of viability, invasion, and migration of A549 cells, respectively. ACSL4 and SLC7A11 were associated with ferroptosis, MMP 9, vimentin, and E-cadherin, which were associated with migration and invasion and were assessed by WB and qRT-PCR. Fe2+ and malondialdehyde (MDA) were analyzed using kits.
ResultsOver-expression of HCP5 enhances the growth, invasion, and migration of A549 cells by adjusting miR-17-5P to increase the expression of HOXA7. In addition, the knockdown of HCP5 elevated miR-17-5p, which inhibited HOXA7 expression and suppressed ferroptosis and EMT in A549 cells.
ConclusionHCP5/miR-17-5p/HOXA7 can affect ferroptosis as well as the biological behavior of A549 cells.
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Liquisolid Technique for Solubility Enhancement of Poorly Soluble Drug - A Brief Review
Authors: Amaresh Prusty, Bikash Ranajn Jena, Vivek Barik, Piyali Khamkat and Bhakti Bhusan BarikAvailable online: 04 October 2024More LessMost of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, non-adherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.
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