Isolation of 6-gingerol and semi-synthesis of 1,4-benzodiazepines derivatives: An in-situ pharmacokinetics properties, molecular docking and molecular dynamics simulation assessments.

This paper outlines a methodical approach for isolating 6-gingerol (1a) from Zingiber officinale Roscoe rhizomes on a gram-scale, resulting in a product of high purity and significant yield. Further, 6-gingerol (1a) [SSG1] derivatives, including 1-(4-hydroxy-3-methoxyphenyl)decane-3,5-dione (1ab), were synthesized via a semi-synthetic pathway involving DMP-mediated fast oxidation and replication. Subsequently, a new series of 1,4-benzodiazepines (3a-c) was synthesized quantitatively using a basic technique. This synthesis necessitated the interaction of 1ab with various o-phenylenediamine (2a-c) compounds. Spectroscopic methods were employed to characterize the synthesized 1,4-benzodiazepines (3a-c)[SSG2, SSG3 & SSG4]. Despite extensive investments by pharmaceutical companies in traditional drug research and development for diseases like type 2 diabetes (T2D), successful treatments remain elusive. Medication repurposing has gained traction as a strategy to address not only diabetes but also other disorders. Leveraging existing molecular pharmacology data accelerates the development of new medications. This paper underscores the importance of repurposing traditional medicines to combat a range of communicable and non-communicable diseases, offering a promising avenue for therapeutic advancement. Additionally, molecular docking studies suggested that one derivative (SSG2) exhibited stronger binding affinity compared to the reference standards. Overall, the findings of this study highlight the potential of semi-synthetic gingerol derivatives for the development of novel therapeutic agents.

Unraveling the therapeutic potential of quercetin and quercetin-3-O-glucuronide in Alzheimer's disease through network pharmacology, molecular docking, and dynamic simulations.

Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. Quercetin plays a significant role in neuroinflammation, which helps reduce Alzheimer's disease (AD) severity. Quercetin (Q) and quercetin 3-O-glucuronide (Q3OG) are some of the most potent antioxidants available from natural sources. However, the natural form of quercetin converted into Q3OG when reacted with intestinal microbes. The study aims to ensure the therapeutic potential of Q and Q3OG. In this study, potential molecular targets of Q and Q3OG were first identified using the Swiss Target Prediction platform and pathogenic targets of AD were identified using the DisGeNET database. Followed by compound and disease target overlapping, 77 targets were placed in that AKT1, EGFR, MMP9, TNF, PTGS2, MMP2, IGF1R, MCL1, MET and PARP1 was the top-ranked target, which was estimated by CytoHubba plug-in. The Molecular docking was performed for Q and Q3OG towards the PDB:1UNQ target. The binding score of Q and Q3OG was - 6.2 kcal/mol and - 6.58 kcal/mol respectively. Molecular dynamics simulation was conducted for Q and Q3OG towards the PDB:1UNQ target at 200 ns. This study's results help identify the multiple target sites for the bioactive compounds. Thus, synthesizing new chemical entity-based quercetin on structural modification may aid in eradicating AD complications.

Deciphering the gut microbiota's (Coprococcus and Subdoligranulum) impact on depression: Network pharmacology and molecular dynamics simulation.

Depression, a prevalent mental health condition, significantly impacts global mental impairment rates. While antidepressants are commonly used, treatment-resistant depression (TRD) poses a challenge. Emerging research highlights the role of the gut microbiota in depression through the gut-brain axis. This study identifies key genes associated with depression influenced by specific gut microbiota, Coprococcus and Subdoligranulum. Using bioinformatics tools, potential targets were elucidated, and molecular docking studies were performed. Furthermore, gene expression analysis identified hub-genes related to depression, intersecting with metabolite targets. Protein-protein interaction analysis revealed pivotal targets such as PTGS2 and MMP9. Molecular docking demonstrated 3-Indolepropionic acid's superior affinity over (R)-3-(4-Hydroxyphenyl)lactate. Physicochemical properties and toxicity profiles were compared, suggesting favorable attributes for 3-Indolepropionic acid. Molecular dynamics simulations confirmed stability and interactions of compounds with target proteins. This comprehensive approach sheds light on the complex interplay between gut microbiota, genes, and depression, emphasizing the potential for microbiota-targeted interventions in mental health management.

GC-MS analysis of an ethanolic extract of Ocimum species: a network pharmacology analysis insight towards obesity.

Aim: In this study, we have selected two different Ocimum tenuiflorum plants, Ocimum tenuiflorum (Rama tulsi) (OTRT) and Ocimum tenuiflorum (Krishna tulsi) (OTKT). Materials & methods: In the present investigation, ethanol was used as a solvent to estimate the bioactive compounds present in it through gas chromatography-mass spectrometry (GC-MS). Results: Based on the GC-MS data benzenepropanoic acid, 3-methoxy-alpha,4-bis[(trimethylsilyl)oxy was found to be the potent compound in OTRT (MW: 428.74 g/mol) and methyl 3-(4-benzyloxy-3,5-dimethoxyphenyl)-2-methylpropanoate in OTKT (MW: 342.39 g/mol). To estimate its pharmacological application, an integrated Network Pharmacology approach is performed toward the disease target obesity. Conclusion: From the protein-protein interaction from the string database, SRC, BCL2, EGFR, MTOR, CDK1, ERBB2, MAPK1, FYN, AR and MAPK14 are the top-ranked targets.

Haloperidol-induced painless legs and moving toe syndrome in a schizophrenia patient: a case report.

Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's PoLMT is unknown. We present a case of PoLMT in 45-year-old woman with a history of haloperidol intake for 10 months. Haloperidol was discontinued, and aripiprazole (15 mg) was initiated. After this switch, a reduction in movement was observed in the third and fourth toes; however, the second toe showed no discernible change.

Painless Legs and Moving Toe Syndrome (PoLMT) is a rare condition in which the toe moves on its own without any pain. No one knows for sure what causes PoLMT in patients. In this case report, we discuss a 45-year-old woman with PoLMT who was taking a drug called haloperidol for 10 months prior to their visit to hospital. Another drug, aripiprazole, was started after haloperidol was stopped. It was noticed that the third and fourth toes moved less after this switch in medication, but no change was noticed in the second toe.

Network pharmacology based pharmacokinetic assessment and evaluation of the therapeutic potential of catechin derivatives as a potential myostatin inhibitor: A special view on Sarcopenic Obesity.

Sarcopenic obesity has become a significant age-related metabolic problem. Catechins are flavanol, derivatives which poses a strong antioxidant activity. The major components of catechin derivatives. were identified through our physicochemical and pharmacokinetic parameters estimation. Therefore, in this study, network pharmacology was used to explore the multiple targets related to Sarcopenia, Metabolic syndrome, and obesity. The targets were identified from network analysis. The catechin derivatives were screened using Lipinski's rule of five, Veber scale, Egan scale, and Muegge scale. From this drugglikness property catechin and Epicatechin was selected which were docked towards the myostatin inhibition PDB ID: 3HH2. Furthermore, the computational docking method on Catechin and Epicatechin with the stronger interaction towards myostatin inhibition receptor with the binding energy of -6.90 kcal/mol. and -7.0 kcal/mol from autodock software, respectively, for catechin and Epicatechin. Higher binding energy confirms the pharmacotherapeutic activity of Catechin and Epicatechin toward the myostatin inhibitor target.

A narrative review on Naringin and Naringenin as a possible bioenhancer in various drug-delivery formulations.

Naringenin belongs to the flavanones and is mainly found in fruits (grapefruit and oranges) and vegetables. Naringenin exhibits lipid-lowering and insulin-like characteristics and is used to treat osteoporosis, cancer and cardiovascular disorders. Their incorporation into drug formulations offers several advantages, including enhanced solubility, improved bioavailability and targeted delivery. Naringin-based formulations are beneficial in cancer, for example controlling breast and prostate cancer by inhibition of CYP19. Naringin suppresses the PI3K/AKT signalling pathway, it triggers autophagy, which effectively halts the proliferation of gastric cancer cells. Naringin and naringenin co-administration or pre-administration has enhanced the target drug's potency and produced a synergistic effect. This published study demonstrates the potential applications of Naringin and Naringenin as recognized bio-enhancers.

This work investigates the possible uses of Naringenin, a substance found in fruits such as grapefruit and oranges. Naringenin has some exciting qualities ­ it can help lower lipids (fats), act similarly to insulin, and has the potential to fight cancer. Because of these properties, it could be helpful in treating conditions like osteoporosis, cancer, and heart problems. When we include Naringenin in medicine formulations, it can have benefits such as being easier to dissolve, getting absorbed better by the body, and reaching specific target areas effectively.

Pharmacokinetic correlation of structurally modified chalcone derivatives as promising leads to treat tuberculosis.

In this study, we evaluated the potential of curated structurally modified chalcone derivatives as anti-tuberculosis (TB) agents through computer-aided drug design. Compounds from the flavonoid family known as chalcones were identified by the chemical group 1,3-diaryl-2-propen-1-one. After a search of the literature, 14 outstanding structurally modified chalcones were selected and evaluated for inhibitory activity against Mycobacterium tuberculosis H37Rv targets. The therapeutic potential of the chalcones was directly based on the drug-likeness and pharmacokinetic properties of the synthesized compounds. Prompt drug selection and personalized therapy are required to prevent TB from progressing and spreading to others. Pharmacokinetic parameters helps in the identification of lead molecule, at the earlier stages of drug development.

Synthesis of quercetin-iron (Fe) complex and its in silico and in vitro confirmation towards antibacterial activity.

Aim: In this study quercetin-iron complex (QFC) was synthesized, and the structural characterizations such as x-ray diffraction, field emission-scanning electron microscopy, energy-dispersive x-ray and Brunner-Emmitt-Teller adsorption-desorption isotherm analysis revealed the crystallinity state, surface morphology and nature of the adsorbing surface with surface area value. Methodology: Functional characterizations such as UV-visible spectrometric and Fourier transform infrared analysis collectively indicated the chemical changes that appeared after complex formation in terms of characteristic change in the spectrum and band position, respectively. Results: The in vitro antibacterial activity against Escherichia coli and Staphylococcus aureus has shown a dose-dependent decrease in colony count and achieved significant removal at 15 mg/ml concentration of QFC. Conclusion: The molecular docking study supports the therapeutic application of QFC.

A narrative review on the impact of sarcopenic obesity and its psychological consequence in quality of life.

BACKGROUND AND AIM: Sarcopenia is a multifactorial metabolic-mediated complication that affects most of the geriatric population physically and mentally. In this study, we intended to study the association between sarcopenia and psychologically related symptoms. Primary objective of the study is to explore the interplay between sarcopenic obesity, psychological consequences and Quality of life in the affected population. The secondary objective is to discuss the diagnostic, treatment approaches and also the role of clinical pharmacist. METHOD: The psychology-related complication and sarcopenia association was enumerated in this study based on previous clinical research findings. RESULT: The clinical evidence shows a strong correlation between sarcopenia and Mental health and its health consequences and reflection on the quality of life. CONCLUSION: Sarcopenia induced mental disturbance has been affirmed in many studies. We believe effective right pharmacological therapy and non-pharmacological therapies with respective lifestyle modification advice could be potential vital factors that can reduce further complications in geriatric populations.

Isolation and in-silico approach of Modified Embelin derivative from Embelia ribes fruits as anti-Alzheimer agent.

Embelin is one of the primary compounds present in the Embelia ribes fruit. Embelin has a broader pharmacological activity such as Anti-inflammatory, anti-bacterial, antioxidant, and many more. The ultimate aim of the study is to ensure the impact of reduced embelin in the management of Alzheimer's disease. Embelin was isolated and modified by the reduction method, and the Modified Embelin derivative (MED) 3-Undecylcyclohexa-2,5-diene-1,2,4,5-tetraol was analysed through FT-IR, NMR, and Mass Spectroscopic techniques. MED was docked against acetylcholinesterase (AChE) amyloid beta (Aß) receptors PDB ID: 1EVE & 1B68, respectively. The docking scores remain similar to that of positive standards galantamine and Donepezil.

Physicochemical investigation and molecular docking analysis of Maha yogaraj Guggulu tablet and virtual screening of its major bioactive compound.

Guggulsterone plays a significant role in cholesterol-lowering by inhibiting Farnesoid X Receptor. The present study aims to identify the isomers of Guggulsterone with high binding affinity and good binding interaction with targeted protein and positive control atorvastatin. The pharmacokinetic parameters of Guggulsterone isomers were estimated from P.K.C.S.M. online server, and molecular docking analysis was performed from Autodock V.® 4.2.6 Program. From the computer-aided drug designing, we have confirmed that guggulsterone isomers are inhibitors of the CYP3A4 enzyme and hepatotoxic. Guggulsterone isomer showed a stronger binding affinity when compared with atorvastatin. The docking score for Guggulsterone was -9.28 kcal/mol, E-Guggulsterone -9.56 kcal/mol, Z-Guggulsterone -9.79 kcal/mol, M-Guggulsterone -9.45 kcal/mol, and positive control atorvastatin -8.26 kcal/mol. The present study revealed that the isomers of Guggulsterone have high binding affinity and good binding interaction with targeted proteins.

Insight on sarcopenic obesity and epicatechin as a promising treatment option.

BACKGROUND AND AIM: Sarcopenic Obesity (SO) in the elderly population is a complex and multifactorial condition which refers to the loss of skeletal muscle mass, strength, and function associated with aging, while obesity involves excessive adipose tissue accumulation. The simultaneous occurrence of these two conditions presents a unique set of challenges to public health and clinical management. This narrative review aims to provide an overview of the use of epicatechin (EC) in the treatment of SO and its related complications. METHOD: A survey of studies related to preclinical and clinical evidence of Epicatechin in sarcopenic obesity and its complications was performed in the following database Medline, Scopus, ProQuest, Embase, Web of Science, and Google scholar. Followed by structural activity relationship and pharmacokinetic profile of Epicatechin was discussed in this paper. RESULTS: The main pharmacological effect of Epicatechin is myostatin inhibition activity which has been described by both in vitro and in vivo studies earlier. The SO is directly correlated with the alteration of Myostatin. The pre-clinical and clinical studies suggest that epicatechin can be a potential candidate in the management of SO and its related complication. CONCLUSION: The present review describes the pharmacokinetic profile and structural activity of epicatechin respective to SO and its related complications. The goal of this review is to update the scientific community on the therapeutic potential of epicatechin in SO and age-related factors. Conduction of clinical and pre-clinical trials, also drug dosage optimization may provide with insights on the use of epicatechin in SO.

Chalcones reloaded: an integration of network pharmacology and molecular docking for type 2 diabetes therapy.

Chalcones have various biological effects, from immune boosting to anti-cancer and anti-diabetic. Structurally modified chalcones (SMC) are clinically relevant for diabetes and cardiometabolic complications. From the original research articles, a structurally proven and biologically outstanding 14 structurally modified chalcones were screened and inducted in this study. This study evaluated the effects of SMC towards diabetes via network pharmacology analysis. The network data shows compounds S2, S3, S5, S9 &S12 suit the diabetes target. Especially Compounds S5 and S9 have a higher binding affinity towards the targets of TNF, PI3K, MAPK1 and AKT1 active sites. Compound S9 [(E)-3-(4-(1H-imidazol-1-yl)phenyl)-1-(4-(2,4-difluorobenz-yloxy)phenyl)prop-2-en-1-one] have identified with stronger binding affinities towards the active sites of MAPK3 (PDB:4QTB) -10.5(Kcal/mol). To provide a more effective mechanism for demonstrating protein-ligand interaction, one of the molecular docking complex (ERK2 kinase-S5) was subjected to a molecular dynamic at 300K for 100 ns. In term of structural stability, structure compactness, residual flexibility and hydrogen bond interaction of the complex was evaluated Integrating network pharmacology, in silico virtual screening, and molecular docking analysis shows that structurally modified compounds are effective and may help identify lead compounds towards glycemic control.Communicated by Ramaswamy H. Sarma.

Drug designing and toxicity screening of halogen and nitrogen-augmented catechin in sarcopenic obesity.

In this study, the catechin structure was modified with Halogen and Nitrogen base at C-6 and C-8 Positions in Ring A. Pharmacokinetic parameters affirm the drug-likeness property of the designed compounds. Molecular Docking was performed for all the compounds towards the myostatin inhibition target (PDB: 3HH2). Such desirable quality of modified Catechin will create a spark in the novel drug discovery using acting as a bioenhancer. As a result, the present research is aimed to offer an overview of the structural simulation of Cl, F, I, NH2, NO2, and Br at C-6 and C-8 positions in A Ring A of Catechin. This preliminary evidence creates an impact on the novelsemi0synthetic drug discovery for the therapeutic management of sarcopenia.

A computer-aided insight into the identification of significant therapeutic flavone as a promising agent for sarcopenic obesity.

Polyphenols, the important secondary metabolites, consist of multiple phytochemicals and show numerous physiological effects. Flavones play a significant role in various chronic disorders such as diabetes.. In this study, all the flavones were encountered, and it was further filtered based on their drug-likeness properties and pharmacokinetic parameters. Existing literature confirms that flavone-based compounds are suitable as the drug of choice in sarcopenic obesity. A molecular docking study was performed toward the myostatin inhibition profile of the flavones using PDB:3HH2 as a target site. This computer-aided drug design helps select lead molecules in novel drug discovery.

Synthesize palladium nanoparticles from the macroalgae Sargassum fusiforme: An eco-friendly tool in the fight against Plasmodium falciparum?

Although numerous drugs are practiced to control malaria and its vectors, more recently, eco-friendly control tools have been proposed to battle its etiologic agents. Thus, using green bionanotechnology approaches, we aimed to synthesize palladium nanoparticles (Pd NPs) from the macroalgae Sargassum fusiforme (Sf), its potential antiparasitic activity against P. falciparum, as well as its possible cytotoxicity, in HeLa cells. After the biosynthesis of the PdSf NPs, their characterization was carried out by UV-Vis, FESEM, and EDX analyses, and their hydrodynamic size, zeta potential, and surface area were determined. Furthermore, the functional groups of the PdSf NPs were analyzed by FT-IR and GC-MS. While PdSf NPs had an IC50 of 7.68 µg/mL (Chloroquine (CQ)-s) and 16.42 µg/mL, S. fusiforme extract had an IC50 of 14.38 µg/mL (CQ-s) and 35.27 µg/mL (CQ-r). With an IC50 value of 94.49 µg/mL, PdSf NPs exhibited the least toxic effect on the HeLa cells. The Lipinski rule of five and ADMET prediction were used to assess the in silico models of caffeine acid hexoside and quercetin 7-O-hexoside for the presence of drug-like properties. Pathogenic proteins, primarily responsible for motility, binding, and disease-causing, were the target of the structurally based docking studies between plant-derived compounds and pathogenic proteins. Thus, our study pioneered promising results that support the potential antiplasmodial activity of eco-friendly synthesized PdSf NPs using S. fusiforme extract against P. falciparum, opening perspectives for further exploration into the use of these NPs in malaria therapy.

Isolation and In silico Study of Curcumin from Curcuma longa and Its Anti-Diabetic Activity.

Natural products have been widely used for the management of various diseases that affect human health. Natural products are chemical substances that can be extracted with solvents and isolated by column chromatography techniques from the plant source. The development of new drugs from natural products is still challenging, and the most extensively studied plant material is turmeric, Curcuma longa, which is the chief source of curcumin. Curcumin is a bright yellow solid. In our present study, we have taken Curcuma longa, which is defatted with hexane, followed by being extracted with methanol as a solvent. The turmeric methanolic extract is taken for the isolation of curcumin. This was carried out and confirmed by spectroscopy techniques including 1H NMR, 13C NMR, ESI-HRMS, and FT-IR. The compound in silico ADME properties estimate falls within an acceptable range, and a molecular docking analysis shows that it has a higher binding affinity than reference standards. Based on the findings, it can be said that curcumin, a natural substance, has good therapeutic qualities when it is isolated.