Exploring nature's hidden treasure: Unraveling the untapped phytochemical and pharmacological potentials of Clinopodium vulgare L. - A hidden gem in the Lamiaceae family.

Folk medicine, rooted in historical practice, has long been used for medicinal purposes, emphasizing the need to ensure the safety, quality, and efficacy of herbal medicines. This imperative has grown over time, prompting collaborative efforts to document historical records and preserve invaluable knowledge of medicinal plants. The Lamiaceae (Labiatae) family, renowned for its rich assortment of medicinal plants characterized by high concentrations of volatile oils, stands out in this regard. This review focuses on Clinopodium vulgare (C. vulgare) L., commonly known as wild basil or basil thyme, a significant species within the Lamiaceae family found across diverse global regions. C. vulgare boasts a storied history of application in treating various ailments, such as gastric ulcers, diabetes, and inflammation, dating back to ancient times. Rigorous research has substantiated its pharmacological properties, revealing its antioxidant, antiviral, antibacterial, anti-inflammatory, anticancer, antihypertensive, and enzyme-inhibitory effects. This comprehensive review provides an insightful overview of the Lamiaceae family, elucidates the extraction methods employed to obtain medicinal compounds, explores the phytoconstituents present in C. vulgare, and systematically details its diverse pharmacological properties. Additionally, the review delves into considerations of toxicity. By synthesizing this wealth of information, this study opens avenues for the potential therapeutic applications of C. vulgare. The practical value of this research lies in its contribution to the understanding of medicinal plants, mainly focusing on the pharmacological potential of C. vulgare. This exploration enriches our knowledge of traditional medicine and paves the way for innovative therapeutic approaches, offering promising prospects for future drug development. As the demand for natural remedies continues to increase, this work provides a valuable resource for researchers, practitioners, and stakeholders in herbal medicine and pharmacology.

Targeting Sirtuin 1 for therapeutic potential: Drug repurposing approach integrating docking and molecular dynamics simulations.

Identifying novel therapeutic agents is a fundamental challenge in contemporary drug development, especially in the context of complex diseases like cancer, neurodegenerative disorders, and metabolic syndromes. Here, we present a comprehensive computational study to identify potential inhibitors of SIRT1 (Sirtuin 1), a critical protein involved in various cellular processes and disease pathways. Leveraging the concept of drug repurposing, we employed a multifaceted approach that integrates molecular docking and molecular dynamics (MD) simulations to predict the binding affinities and dynamic behavior of a diverse set of FDA-approved drugs from DrugBank against the SIRT1. Initially, compounds were shortlisted based on their binding affinities and interaction analyses to identify safe and promising binding partners for SIRT1. Among these candidates, Doxercalciferol and Timiperone emerged as potential candidates, displaying notable affinity, efficiency, and specificity towards the binding pocket of SIRT1. Extensive evaluation revealed that these identified compounds boast a range of favorable biological properties and prefer binding to the active site of SIRT1. To delve deeper into the interactions, all-atom MD simulations were conducted for 500 nanoseconds (ns). These simulations assessed the conformational dynamics, stability, and interaction mechanism of the SIRT1-Doxercalciferol and SIRT1-Timiperone complexes. The MD simulations illustrated that the SIRT1-Doxercalciferol and SIRT1-Timiperone complexes maintain stability over a 500 ns trajectory. These insightful outcomes propose that Doxercalciferol and Timiperone hold promise as viable scaffolds for developing potential SIRT1 inhibitors, with implications for tackling complex diseases such as cancer, neurodegenerative disorders, and metabolic syndromes.

Neuroprotective potential of Marsilea quadrifolia Linn against monosodium glutamate-induced excitotoxicity in rats.

Background: Excitotoxicity is a condition in which neurons are damaged/injured by the over-activation of glutamate receptors. Excitotoxins play a crucial part in the progression of several neurological diseases. Marsilea quadrifolia Linn (M. quadrifolia) is a very popular aquatic medicinal plant that has been utilised for a variety of therapeutic benefits since ancient times. Its chemical composition is diverse and includes phenolic compounds, tannins, saponins, flavonoids, steroids, terpenoids, alkaloids, carbohydrates and several others that possess antioxidant properties. Objective: The objective of the present study was to investigate the neuroprotective potential of M. quadrifolia against monosodium glutamate (MSG)-induced excitotoxicity in rats. Methods: A high-performance thin-layer chromatography (HPTLC) analysis of chloroform extract of M. quadrifolia (CEMQ) was conducted to identify the major constituents. Further, the in silico docking analysis was carried out on selected ligands. To confirm CEMQ's neuroprotective effects, the locomotor activity, non-spatial memory, and learning were assessed. Results and discussion: The present study confirmed that CMEQ contains quercetin and its derivatives in large. The in-silico findings indicated that quercetin has a better binding affinity (-7.9 kcal/mol) towards the protein target 5EWJ. Animals treated with MSG had 1) a greater reduction in the locomotor score and impairment in memory and learning 2) a greater increase in the blood levels of calcium and sodium and 3) neuronal disorganization, along with cerebral edema and neuronal degeneration in the brain tissues as compared to normal control animals. The changes were however, significantly improved in animals which received standard drug memantine (20 mg/kg) and CEMQ (200 and 400 mg/kg) as compared to the negative control. It is plausible that the changes seen with CEMQ may be attributed to the N-methyl-D-aspartate (NMDA) antagonistic properties. Conclusion: Overall, this study indicated that M. quadrifolia ameliorated MSG-induced neurotoxicity. Future investigations are required to explore the neuroprotective mechanism of M. quadrifolia and its active constituents, which will provide exciting insights in the therapeutic management of neurological disorders.

Unveiling Phytoconstituents with Inhibitory Potential Against Tyrosine-Protein Kinase Fyn: A Comprehensive Virtual Screening Approach Targeting Alzheimer's Disease.

BACKGROUND: Tyrosine-protein kinase Fyn (Fyn) is a critical signaling molecule involved in various cellular processes, including neuronal development, synaptic plasticity, and disease pathogenesis. Dysregulation of Fyn kinase has been implicated in various complex diseases, including neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as different cancer types. Therefore, identifying small molecule inhibitors that can inhibit Fyn activity holds substantial significance in drug discovery. OBJECTIVE: The aim of this study was to identify potential small-molecule inhibitors among bioactive phytoconstituents against tyrosine-protein kinase Fyn. METHODS: Through a comprehensive approach involving molecular docking, drug likeliness filters, and molecular dynamics (MD) simulations, we performed a virtual screening of a natural compounds library. This methodology aimed to pinpoint compounds potentially interacting with Fyn kinase and inhibiting its activity. RESULTS: This study finds two potential natural compounds: Dehydromillettone and Tanshinone B. These compoundsdemonstrated substantial affinity and specific interactions towards the Fyn binding pocket. Their conformations exhibitedcompatibility and stability, indicating the formation of robust protein-ligand complexes. A significant array of non-covalentinteractions supported the structural integrity of these complexes. CONCLUSION: Dehydromillettone and Tanshinone B emerge as promising candidates, poised for further optimization as Fynkinase inhibitors with therapeutic applications. In a broader context, this study demonstrates the potential of computationaldrug discovery, underscoring its utility in identifying compounds with clinical significance. The identified inhibitors holdpromise in addressing a spectrum of cancer and neurodegenerative disorders. However, their efficacy and safety necessitatevalidation through subsequent experimental studies.

Identifying ß-secretase 1 (BACE1) inhibitors from plant-based compounds: an approach targeting Alzheimer's therapeutics employing molecular docking and dynamics simulation.

ß-secretase 1 (BACE1) is an enzyme that is involved in generating beta-amyloid peptides and is believed to have a significant role in the development of Alzheimer's disease (AD). Therefore, BACE1 has gained attention as a potential therapeutic target for treating AD. Modern drug discovery studies are being conducted to identify potential inhibitors of BACE1, with the goal of reducing the production of beta-amyloid peptides and, thus, slowing the progression of AD. Here, we used a multistep virtual screening methodology to identify phytoconstituents from the IMPPAT library that could inhibit the activity of BACE1. Molecular docking was employed to select initial hits based on their binding affinity toward BACE1. Screening for PAINS patterns, ADMET and PASS properties, was then used to identify potential molecules for BACE1 inhibition. In the end, we discovered two natural compounds, Peiminine and 27-Deoxywithaferin A, which demonstrated a strong affinity, effectiveness, and specific interactions for the BACE1-active site. The elucidated molecules also displayed drug likeliness. A 200 ns molecular dynamics (MD) simulation was conducted to investigate the interaction mechanism, complex stability, and conformational dynamics of BACE1 with Peiminine and 27-Deoxywithaferin A. The MD simulations demonstrated that BACE1 was stable during the simulation with Peiminine and 27-Deoxywithaferin A. Overall, the results suggested that Peiminine and 27-Deoxywithaferin A hold significant potential as scaffolds in drug development efforts targeting BACE1 for the purpose of treating AD.

Unveiling promising inhibitors of superoxide dismutase 1 (SOD1) for therapeutic interventions.

Superoxide dismutase 1 (SOD1) is a vital enzyme responsible for controlling cellular oxidative stress. Any dysregulation of SOD1 activity is linked with cancer pathogenesis and neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS). Among the inhibitors known to be effective against SOD1, LCS-1 stands out; however, its efficacy, specificity, and safety profiles are somewhat restricted. In this study, we used PubChem library to retrieve compounds that exhibited a structural similarity of at least 90 % with LCS-1. These compounds underwent molecular docking analyses to examine their interaction patterns and binding affinities with SOD1. Further, we applied filters based on physicochemical and ADMET properties, refining the selection process. Our analysis revealed that selected compounds interact with crucial residues of SOD1 active site. To gain further insights into conformational stability and dynamics of the SOD1-ligand complexes, we conducted all-atom molecular dynamics (MD) simulations for 100 ns. We identified two compounds, CID:133306073 and CID:133446715, as potential scaffolds with promising inhibitory properties against SOD1. Both compounds hold significant potential for further exploration as therapeutic SOD1 inhibitors. Further studies are warranted to fully harness their therapeutic potential in targeting SOD1 for cancer and ALS treatment, offering new avenues for improved patient outcomes and disease management.

PF543-like compound, a promising sphingosine kinase 1 inhibitor: Structure-based virtual screening and molecular dynamic simulation approaches.

Sphingosine kinase 1 (SphK1) has been widely recognized as a significant contributor to various types of cancer, including breast, lung, prostate, and hematological cancers. This research aimed to find a potential SphK1 inhibitor through a step-by-step virtual screening of PF543 (a known SphK1 inhibitor)-like compounds obtained from the PubChem library with the Tanimoto threshold of 80 %. The virtual screening process included several steps, namely physicochemical and ADMET evaluation, PAINS filtering, and molecular docking, followed by molecular dynamics (MD) simulation and principal component analysis (PCA). The results showed that compound CID:58293960 ((3R)-1,1-dioxo-2-[[3-[(4-phenylphenoxy)methyl]phenyl]methyl]-1,2-thiazolidine-3-carboxylic acid) demonstrated high potential as SphK1 inhibitor. All-atom MD simulations were performed for 100 ns to evaluate the stability and structural changes of the docked complexes in an aqueous environment. The analysis of the time evolution data of structural deviations, compactness, PCA, and free energy landscape (FEL) indicated that the binding of CID:58293960 with SphK1 is relatively stable throughout the simulation. The results of this study provide a platform for the discovery and development of new anticancer therapeutics targeting SphK1.

Insight into the Biological Roles and Mechanisms of Phytochemicals in Different Types of Cancer: Targeting Cancer Therapeutics.

Cancer is a hard-to-treat disease with a high reoccurrence rate that affects health and lives globally. The condition has a high occurrence rate and is the second leading cause of mortality after cardiovascular disorders. Increased research and more profound knowledge of the mechanisms contributing to the disease's onset and progression have led to drug discovery and development. Various drugs are on the market against cancer; however, the drugs face challenges of chemoresistance. The other major problem is the side effects of these drugs. Therefore, using complementary and additional medicines from natural sources is the best strategy to overcome these issues. The naturally occurring phytochemicals are a vast source of novel drugs against various ailments. The modes of action by which phytochemicals show their anti-cancer effects can be the induction of apoptosis, the onset of cell cycle arrest, kinase inhibition, and the blocking of carcinogens. This review aims to describe different phytochemicals, their classification, the role of phytochemicals as anti-cancer agents, the mode of action of phytochemicals, and their role in various types of cancer.

Inhibition of microtubule affinity regulating kinase 4 by an acetylcholinesterase inhibitor, Huperzine A: Computational and experimental approaches.

Microtubule affinity regulating kinase 4 (MARK4), 752 amino acids long, belonging to the AMPK superfamily, plays a vital role in regulating microtubules due to its potential to phosphorylate microtubule-associated proteins (MAP's) and thus, MARK4 plays a key role in Alzheimer's disease (AD) pathology. MARK4 is a druggable target for cancer, neurodegenerative diseases, and metabolic disorders. In this study, we have evaluated the MARK4 inhibitory potential of Huperzine A (HpA), an acetylcholinesterase inhibitor (AChEI), a potential AD drug. Molecular docking revealed the key residues governing the MARK4-HpA complex formation. The structural stability and conformational dynamics of the MARK4-HpA complex was assessed by employing Molecular dynamics (MD) simulation. The results suggested that the binding of HpA with MARK4 leads to minimal structural alterations in the native conformation of MARK4, implying the stability of the MARK4-HpA complex. Isothermal titration calorimetry (ITC) studies deciphered that HpA binds to MARK4 spontaneously. Moreover, the kinase assay depicted significant inhibition of MARK by HpA (IC50 = 4.91 µM), implying it to be a potent MARK4 inhibitor that can be implicated in the treatment of MARK4-directed diseases.

Medicinal Plants as Therapeutic Alternatives to Combat Mycobacterium tuberculosis: A Comprehensive Review.

Tuberculosis (TB) is a serious infectious disease caused by Mycobacterium tuberculosis (MTB) and a significant health concern worldwide. The main threat to the elimination of TB is the development of resistance by MTB to the currently used antibiotics and more extended treatment methods, which is a massive burden on the health care system. As a result, there is an urgent need to identify new, effective therapeutic strategies with fewer adverse effects. The traditional medicines found in South Asia and Africa have a reservoir of medicinal plants and plant-based compounds that are considered another reliable option for human beings to treat various diseases. Abundant research is available for the biotherapeutic potential of naturally occurring compounds in various diseases but has been lagging in the area of TB. Plant-based compounds, or phytoproducts, are being investigated as potential anti-mycobacterial agents by reducing bacterial burden or modulating the immune system, thereby minimizing adverse effects. The efficacy of these phytochemicals has been evaluated through drug delivery using nanoformulations. This review aims to emphasize the value of anti-TB compounds derived from plants and provide a summary of current research on phytochemicals with potential anti-mycobacterial activity against MTB. This article aims to inform readers about the numerous potential herbal treatment options available for combatting TB.

Linagliptin and Empagliflozin Inhibit Microtubule Affinity Regulatory Kinase 4: Repurposing Anti-Diabetic Drugs in Neurodegenerative Disorders Using In Silico and In Vitro Approaches.

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) are significant public health burdens. Many studies have revealed the possibility of common pathophysiology between T2DM and AD. Thus, in recent years, studies deciphering the action mechanism of anti-diabetic drugs with their future use in AD and related pathologies are on high demand. Drug repurposing is a safe and effective approach owing to its low cost and time-saving attributes. Microtubule affinity regulating kinase 4 (MARK4) is a druggable target for various diseases and is found to be linked with AD and diabetes mellitus. MARK4 plays a vital role in energy metabolism and regulation and thus serves as an irrefutable target to treat T2DM. The present study was intended to identify the potent MARK4 inhibitors among FDA-approved anti-diabetic drugs. We performed structure-based virtual screening of FDA-approved drugs to identify the top hits against MARK4. We identified five FDA-approved drugs having an appreciable affinity and specificity toward the binding pocket of MARK4. Among these identified hits, two drugs, linagliptin, and empagliflozin, favorably bind to the MARK4 binding pocket, interacting with its critical residues and thus subjected to detailed analysis. All-atom detailed molecular dynamics (MD) simulations revealed the dynamics of binding of linagliptin and empagliflozin with MARK4. Kinase assay showed significant inhibition of MARK4 kinase activity in the presence of these drugs, implying them as potent MARK4 inhibitors. In conclusion, linagliptin and empagliflozin may be promising MARK4 inhibitors, which can further be exploited as potential lead molecules against MARK4-directed neurodegenerative diseases.

A virtual screening investigation to identify bioactive natural compounds as potential inhibitors of cyclin-dependent kinase 9.

Cyclin-dependent kinase 9 (CDK9) is a transcription-associated protein involved in controlling the cell cycle and is often deregulated in stress conditions. CDK9 is being studied as a well-known druggable target for developing effective therapeutics against a wide range of cancer, cardiac dysfunction and inflammatory diseases. Owing to the significance of CDK9 in the etiology of hematological and solid malignancies, its structure, biological activity, regulation and its pharmacological inhibition are being explored for therapeutic management of cancer. We employed a structure-based virtual high-throughput screening of bioactive compounds from the IMPPAT database to discover potential bioactive inhibitors of CDK9. The preliminary results were obtained from the Lipinski criteria, ADMET parameters and sorting compounds without any PAINS patterns. Subsequently, binding affinity and selectivity analyses were used to find effective CDK9 hits. This screening resulted in the identification of two natural compounds, Glabrene and Guggulsterone with high affinity and specificity for the CDK9 binding site. Both compounds exhibit drug-like characteristics, as projected by ADMET analysis, physicochemical data and PASS evaluation. Both compounds preferentially bind to the ATP-binding pocket of CDK9 and interact with functionally important residues. Further, the dynamics and consistency of CDK9 interaction with Glabrene and Guggulsteron were evaluated through all-atom molecular dynamic (MD) simulations which suggested the stability of both complexes. The results might be deployed to introduce novel CDK9 inhibitors that may treat life-threatening diseases, including cancer.Communicated by Ramaswamy H. Sarma.

Role of lisinopril in the therapeutic management of cardiovascular disease by targeting microtubule affinity regulating kinase 4: molecular docking and molecular dynamics simulation approaches.

Cardiovascular diseases (CVDs) are a major cause of premature adult death. Various factors contribute to the development of CVDs, such as atherosclerosis leading to myocardial infarction (MI), and compromised cardiac function after MI leads to chronic heart failure with systemic health complications and a high mortality rate. Microtubule detyrosination has rapidly evolved as an essential mechanism to regulate cardiomyocyte contractility. Microtubule affinity regulating kinase 4 (MARK4) regulates cardiomyocyte contractility in a way that it promotes phosphorylation of microtubule-associated protein 4, thereby facilitating the access of vasohibin 2-a tubulin carboxypeptidase-to microtubules for the detyrosination of α-tubulin. Lisinopril, a drug belonging to the class of angiotensin-converting enzyme inhibitors, is used to treat high blood pressure. This is also used to treat heart failure, which plays a vital role in improving the survival rate post-heart attack. In this study, we will evaluate the MARK4 inhibitory potential of lisinopril employing molecular docking and molecular dynamics (MD) simulation approaches. Molecular docking analysis suggested that lisinopril binds to MARK4 with a significant binding affinity forming interactions with functionally essential residues of MARK4. Additionally, MD simulation deciphered the structural dynamics and stability of the MARK4-lisinopril complex. The findings of MD studies established that minimal structural deviations are observed during simulation, affirming the stability of the MARK4-lisinopril complex. Altogether, this study demonstrates lisinopril's crucial role in the therapeutic management of CVD by targeting MARK4.Communicated by Ramaswamy H. Sarma.

A phenylpropanoid dimer from the leaves of Piper betle.

Phytochemical analyses of the chloroform extract of Piper betle L. var. Sanchi, Piperaceae, leaves led to the isolation of a new phenylpropanoid analogue for the first time: hydroxychavicol dimer, 2-(γ'-hydroxychavicol)-hydroxychavicol (S1), on the basis of spectroscopic data 1 D (1H and 13C) and 2 D (1H-1H COSY and HMBC) NMR, as well as ESI-MS, FT-IR, HR-ESI-MS and LC-ESI-MS. Compound S1 exhibited excellent antioxidant DPPH radical scavenging activity with IC50 values of 9.07 µg/mL, compared to ascorbic acid as a standard antioxidant drug with IC50 value of 3.41 µg/mL. Evaluation of cytotoxic activity against two human colon cancer cell lines (HT 29 and COLO-205) showed significant effect with GI50 values of 73.81 and 64.02 µmol/L, compared to Doxorubicin® as a standard cytotoxic drug with GI50 value of <10 µmol/L.

Influence of solvent selection and extraction methods on the determination of polyphenols, antioxidant, lipoxygenase and tyrosinase inhibition activities of Opuntia ficus-indica fruits peel and pulp collected from the Kingdom of Saudi Arabia (KSA).

The effect of extracting solvents used by two methods on the TPC, TFC, antioxidant as well as lipoxygenase, and tyrosinase inhibition activities of O. ficus-indica fruit (peel and pulp) were studied. The results manifest that extracts with solvent polarities showed different levels of polyphenols contents and antioxidant activities. The extracts acquired by the Soxhlet method were the most fascinating. Interestingly, peel extracts contain more polyphenols than pulp and showed activities. Lipoxygenase and tyrosinase inhibitory activity of the fruit peel and pulp extracts was reported for the first time. The promising results obtained prompted to the formulation of a stable phytocosmetic emulsion system loaded with 1% pre-concentrated peel extract, aiming to revive facial skin properties. The efficacy of the formulations was determined through SPF and UVA protection factors. To the in vitro safety assessment CAM-TBS, HET-CAM, and red blood cell tests were achieved. Importantly, the formulation did not induce any toxicity.

Lopinavir-Loaded Self-Nanoemulsifying Drug Delivery System for Enhanced Solubility: Development, Characterisation and Caco-2 Cell Uptake.

BACKGROUND: The antiretroviral protease inhibitor drug, lopinavir (LPV), is used to treat HIV-1 infection. LPV is known to have limited oral bioavailability, which may be attributed to its poor aqueous solubility, low efficacy and high first-pass metabolism. Self-nanoemulsifying drug delivery systems (SNEDDS) for LPV have been developed and optimised to counter the current issues. METHODS: The titration method was used to prepare LPV-loaded SNEDDS (LPV-SNEDDS). Six different pseudo-ternary phase diagrams were constructed to identify the nanoemulsifying region. The developed formulations were chosen in terms of globule size < 100 nm, dispersity ≤ 0.5, dispersibility (Grade A) and% transmittance > 85. Heating-cooling cycle, freeze-thaw cycle, and centrifugation studies were performed to confirm the stability of the developed SNEDDS. RESULTS: The final LPV-SNEDDS (L-14) droplet size was 58.18 ± 0.62 nm, with polydispersity index, zeta potential, and entrapment efficiency (EE%) values of 0.326 ± 0.005, -22.08 ± 1.2 mV, and 98.93 ± 1.18%, respectively. According to high-resolution transmission electron microscopy (HRTEM) analysis, the droplets in the optimised formulation were < 60 nm in size. The selected SNEDDS released nearly 99% of the LPV within 30 min, which was significantly (p < 0.05) higher than the LPV-suspension in methylcellulose (0.5% w/v). It indicates the potential use of SNEDDS to enhance the solubility of LPV, which eventually could help improve the oral bioavailability of LPV. The Caco-2 cellular uptake study showed a significantly (p < 0.05) higher LPV uptake from the SNEEDS (LPV-SNEDDS-L-14) than the free LPV (LPV-suspension). CONCLUSION: The LPV-SNEDDS could be a potential carrier for LPV oral delivery.

Desmodin and isopongachromene as potential inhibitors of cyclin-dependent kinase 5: phytoconstituents targeting anticancer and neurological therapy.

Cyclin-dependent kinase 5 (CDK5) is a proline-directed serine-threonine protein kinase vital for neuronal cell cycle arrest and differentiation. It activates by binding with p35 and p39 and is important for the functioning of the nervous system. A growing body of evidence suggests that CDK5 contributes to the onset and progression of neurodegeneration and tumorigenesis and represents itself as a potential therapeutic target. Our research illustrates virtual screening of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) library to search for potential inhibitors of CDK5. Initially, the compounds from the parent library were filtered out via their physicochemical properties following the Lipinski rule of five. Then sequentially, molecular docking-based virtual screening, PAINS filter, ADMET, PASS analysis, and molecular dynamics (MD) simulation were done using various computational tools to rule out adversities that can cause hindrances in the identification of potential inhibitors of CDK5. Finally, two compounds were selected via the extensive screening showing significant binding with CDK5 ATP-binding pocket and ultimately were selected as potent ATP-competitive inhibitors of CDK5. Finally, we propose that the elucidated compounds Desmodin and Isopongachromene can be used further in the drug discovery process and act as therapeutics in the medical industry to treat certain complex diseases, including cancer and neurodegeneration.Communicated by Ramaswamy H. Sarma.

Brucellosis: epidemiology, pathogenesis, diagnosis and treatment-a comprehensive review.

Background: Brucellosis is a pervasive zoonotic disease caused by various Brucella species. It mainly affects livestock and wildlife and poses significant public health threats, especially in regions with suboptimal hygiene, food safety, and veterinary care standards. Human contractions occur by consuming contaminated animal products or interacting with infected animals. Objective: This study aims to provide an updated understanding of brucellosis, from its epidemiology and pathogenesis to diagnosis and treatment strategies. It emphasizes the importance of ongoing research, knowledge exchange, and interdisciplinary collaboration for effective disease control and prevention, highlighting its global health implications. Methods: Pathogenesis involves intricate interactions between bacteria and the host immune system, resulting in chronic infections characterized by diverse clinical manifestations. The diagnostic process is arduous owing to non-specific symptomatology and sampling challenges, necessitating a fusion of clinical and laboratory evaluations, including blood cultures, serological assays, and molecular methods. Management typically entails multiple antibiotics, although the rise in antibiotic-resistant Brucella strains poses a problem. Animal vaccination is a potential strategy to curb the spread of infection, particularly within livestock populations. Results: The study provides insights into the complex pathogenesis of brucellosis, the challenges in its diagnosis, and the management strategies involving antibiotic therapy and animal vaccination. It also highlights the emerging issue of antibiotic-resistant Brucella strains. Conclusions: In conclusion, brucellosis is a significant zoonotic disease with implications for public health. Efforts should be directed towards improved diagnostic methods, antibiotic stewardship to combat antibiotic resistance, and developing and implementing effective animal vaccination programs. Interdisciplinary collaboration and ongoing research are crucial for addressing the global health implications of brucellosis.