Search

Methicillin-resistant Staphylococcus aureus [MRSA] stands as an enduring threat within healthcare landscapes, characterized by its ability to rapidly evolve and develop resistance to conventional antibiotics. This comprehensive review embarks on a journey through the historical landscape of MRSA, elucidating its initial emergence and subsequent evolution of resistance mechanisms over time. The narrative unfolds to underscore the profound impact of MRSA on patient outcomes and healthcare systems globally. Current trends in MRSA therapies come under meticulous scrutiny, spotlighting the limitations and challenges associated with existing treatment modalities. This analysis underscores the critical need for transformative and innovative therapeutic strategies to effectively combat the ever-growing spectre of drug resistance in MRSA from the exploration of novel antibiotics designed to overcome resistance mechanisms to the promising potential of phage therapy and immunotherapies. Amidst the exploration of innovative therapies, the review identifies and discusses emerging issues and challenges in MRSA management. Insights are provided into the intricate web of obstacles hindering the adoption and implementation of new therapeutic strategies. Furthermore, the socio-economic implications of MRSA and drug resistance are brought to the forefront, emphasizing the broader impact on public health and healthcare systems. In parallel, historical perspectives on MRSA research illuminate key milestones in scientific understanding and technological advancements. The evolution of research strategies and their impact on our ability to comprehend and combat MRSA is examined, providing context for the current state of the field. In conclusion, this review summarizes major findings and drawing implications for the future of MRSA treatment. Recommendations for further research and clinical practice are outlined, encapsulating a holistic overview of the resilient efforts against resistance in the ongoing battle against MRSA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's Disease (AD) is a serious neurodegenerative condition that predominantly impacts the cholinergic neurons of the entorhinal cortex and hippocampal regions, playing a critical role in learning, navigation, and brain processing. This paper aims to discuss the three main hypotheses of Alzheimer's disease, focusing on neurotoxicity and neurodegeneration caused by mitochondrial dysfunction and ROS production, particularly analyzing the susceptibility differences between genders. Our comprehensive review focuses on significant findings from the past five years, particularly on Cholinesterase (ChE) and BACE-1 inhibitors. Researchers have conducted a detailed analysis of in vitro, in silico, and in vivo data, incorporating extensive Structure-Activity Relationship (SAR) studies. The reviewed papers have been sourced from platforms, such as Google Scholar, Semantic Scholar, and ClinicalTrials.gov, and have been selected based on their AChE and BACE-1 inhibitory activity and structural motif similarity. The review identifies the most effective compounds targeting ChE and BACE-1, highlighting acridine, dihydropyridine, and thiazole-coumarin hybrids for ChE inhibition, and oxadiazole, benzofuran, and dihydropyrimidinone for BACE-1 inhibition. This demonstrates a diverse array of potent heterocyclic hybrids. The review presents a varied compilation of scaffolds showing promise in treating Alzheimer's disease, highlighting the potential of specific compounds against ChE and BACE-1. Given the critical insights derived from our analysis, we posit that this compilation will substantially contribute to the ongoing efforts to combat neurodegeneration and prolong dementia, underscoring the importance of continuous research in this domain., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: Neuronal disorders have affected more than 15% of the world's population, signifying the importance of continued design and development of drugs that can cross the Blood-Brain Barrier (BBB)., Background: BBB limits the permeability of external compounds by 98% to maintain and regulate brain homeostasis. Hence, BBB permeability prediction is vital to predict the activity of a drug-like substance., Objective: Here, we report about developing BBBper (Blood-Brain Barrier permeability prediction) using machine learning tool., Method: A supervised machine learning-based online tool, based on physicochemical parameters to predict the BBB permeability of given chemical compounds was developed. The user-end webpage was developed in HTML and linked with back-end server by a python script to run user queries and results., Result: BBBper uses a random forest algorithm at the back end, showing 97% accuracy on the external dataset, compared to 70-92% accuracy of currently available web-based BBB permeability prediction tools., Conclusion: The BBBper web tool is freely available at http://bbbper.mdu.ac.in., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type versus functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRF's interaction is critical for MRTF-A-induced promotion of both two-dimensional and three-dimensional cell migration, while the SAP-domain function is important selectively for three-dimensional cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRF's interaction with MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF-SRF gene signature in pair-matched distant metastases versus primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human BC, justifying future development of specific small molecule inhibitors of the MRTF-SRF transcriptional complex as potential therapeutic agents in BC., Competing Interests: Conflicts of interest: The authors declare no competing conflict of interest.

Cancer stands as a significant global health challenge due to its mortality rates and the complexities involved in its treatment. Addressing issues, such as metastasis, recurrence, chemoresistance, and treatment-related toxicity, remains pivotal in cancer therapy advancement. Therefore, exploration of novel therapeutic agents has emerged as a priority. As the risk of cancer continues to rise, effective measures must be taken to combat it. One promising approach is to explore natural remedies, such as terpenoids, which have demonstrated anticancer activity. Utilizing terpenoids could aid in the development of potent compounds to fight cancer. By studying the structural makeup of various terpenoid derivatives from previous research, we can identify which structural groups are essential for their anticancer activity. This understanding of the structure-activity relationship is crucial for developing new, effective anticancer agents based on terpenoids. Terpenoids, a diverse class of plant-derived secondary metabolites composed of multiple isoprene units, have garnered attention for their potential anticancer and pharmacological qualities. Some terpenoids exhibit notable anticancer effects by concentrating on several stages of cancer development. They show promise in blocking the initiation of early carcinogenesis by the induction of cell cycle arrest, the inhibition of cancer cell differentiation, and the induction of apoptosis. This study delves into the investigation of specific terpenoids showcasing promising anticancer activity against prevalent malignancies, including breast, colon, ovarian, and lung cancers. The study also explores the relationship between the structure and activity of these compounds, which sheds light on how effective they are against a variety of cancer cell types. The comprehensive discussion centres on elucidating terpenoids with substantial potential for combating diverse cancer types, offering insights into their structural features and promising anticancer mechanisms., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Flavonoids are a diversified group of natural substances which were discovered to provide a variety of health benefits in human beings. Vegetables, fruits, wine and tea are the primary flavonoid dietary sources for humans and as the flavonoids are so closely connected to human dietary items and health, it is vital to explore the structural-activity connection. The arrangement, replacement of functional groups, and total number of hydroxyl groups around flavonoid's nucleus structure affect their biological activity, metabolism, and bioavailability. Various flavonoids have been proven to have hepatoprotective properties, that help in the prevention of coronary heart disease. Similarly, these flavonoids also possess anticancer, and anti-inflammatory activities. Flavonoids have been found to have a functional and structural link with their enzyme inhibitory action, that appears to have antiviral effect through acting as antioxidants, damaging cell membranes, blocking enzymes, activating mechanisms of host self-defense, and limiting virus penetration and attaching to cells. Identification, characterization, isolation, and biological role of flavonoids, as well as their uses on health advantages, are all major topics in research and development currently. This review represents a summary of various sources of flavonoids, class, subclass, their chemical structures, biological activities, the pharmacokinetics of flavonoids and various analytical, bioanalytical and electrochemical methods for determination of flavonoids from different matrices.

Dysregulated actin cytoskeleton gives rise to aberrant cell motility and metastatic spread of tumor cells. This study evaluates the effect of overexpression of wild-type vs functional mutants of MRTF-A on migration and invasion of breast cancer (BC) cells. Our studies indicate that SRF's interaction is critical for MRTF-A-induced promotion of both 2D and 3D cell migration, while the SAP-domain function is important selectively for 3D cell migration. Increased MRTF-A activity is associated with more effective membrane protrusion, a phenotype that is attributed predominantly to SRF's interaction of MRTF. We demonstrate formin-family protein mDia2 as an important mediator of MRTF-stimulated actin polymerization at the leading edge and cell migration. Multiplexed quantitative immunohistochemistry and transcriptome analyses of clinical BC specimens further demonstrate a positive correlation between nuclear localization of MRTF with malignant traits of cancer cells and enrichment of MRTF-SRF gene signature in pair-matched distant metastases vs primary tumors. In conclusion, this study establishes a novel mechanism of MRTF-dependent regulation of cell migration and provides evidence for the association between MRTF activity and increased malignancy in human breast cancer, justifying future development of a specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer., Significance: Actin cytoskeletal dysregulation gives rise to metastatic dissemination of cancer cells. This study mechanistically investigates the impact of specific functional disruption of MRTF (a transcriptional co-factor of SRF) on breast cancer cell migration.This study establishes a novel mechanism linking mDia2 to MRTF-dependent regulation of cell migration and provides clinical evidence for the association between MRTF activity and increased malignancy in human breast cancer.Findings from these studies justify future exploration of specific small molecule inhibitor of the MRTF-SRF transcriptional complex as a potential therapeutic agent in breast cancer.

Bone is a frequent site for breast cancer metastasis. Conditioning of the local tumor microenvironment (TME) through crosstalk between tumor cells and bone resident cells in the metastatic niche is a major driving force for bone colonization of breast cancer cells. The vast majority of breast cancer-associated metastasis is osteolytic in nature, and RANKL-induced differentiation of bone marrow-derived macrophages to osteoclasts (OCLs) is a key requirement for osteolytic metastatic growth of cancer cells. In this study, we demonstrate that breast cancer cell-secreted factors stimulate RANKL-induced OCL differentiation of BMDMs requiring the function of Myocardin-related transcription factor (MRTF) in tumor cells. This is partly attributed to the critical role of MRTF in maintaining the basal cellular expression of connective tissue growth factor (CTGF), a pro-osteoclastogenic matricellular factor known to promote bone metastasis in human breast cancer. Supporting these in vitro findings, bioinformatics analyses of multiple human breast cancer transcriptome datasets reveal a strong positive correlation between CTGF expression and MRTF gene signature further establishing the relevance of our findings in a human disease context. By Luminex analyses, we show that MRTF depletion in breast cancer cells has a broad impact on OCL-regulatory cell-secreted factors that extends beyond CTGF. These findings, taken together with demonstration of MRTF-dependence for bone colonization breast cancer cells in vivo, suggest that MRTF inhibition could be an effective strategy to diminish OCL formation and skeletal involvement in breast cancer. In summary, this study highlights a novel tumor-extrinsic function of MRTF relevant to breast cancer metastasis.

Despite recent advances in cancer treatment, refining therapeutic agents remains a critical task for oncologists. Precise evaluation of drug effectiveness necessitates the use of 3D cell culture instead of traditional 2D monolayers. Microfluidic platforms have enabled high-throughput drug screening with 3D models, but current viability assays for 3D cancer spheroids have limitations in reliability and cytotoxicity. This study introduces a deep learning model for non-destructive, label-free viability estimation based on phase-contrast images, providing a cost-effective, high-throughput solution for continuous spheroid monitoring in microfluidics. Microfluidic technology facilitated the creation of a high-throughput cancer spheroid platform with approximately 12 000 spheroids per chip for drug screening. Validation involved tests with eight conventional chemotherapeutic drugs, revealing a strong correlation between viability assessed via LIVE/DEAD staining and phase-contrast morphology. Extending the model's application to novel compounds and cell lines not in the training dataset yielded promising results, implying the potential for a universal viability estimation model. Experiments with an alternative microscopy setup supported the model's transferability across different laboratories. Using this method, we also tracked the dynamic changes in spheroid viability during the course of drug administration. In summary, this research integrates a robust platform with high-throughput microfluidic cancer spheroid assays and deep learning-based viability estimation, with broad applicability to various cell lines, compounds, and research settings.

Background: Infection remains a significant global health concern, with millions of new cases and deaths occurring due to infectious diseases. Currently, chemoprophylaxis and chemotherapy are the primary treatments, but side effects and toxicities pose challenges. Pathogenic microorganisms have developed resistance to antimicrobial medications. Nitrogen containing heterocyclic scaffolds possess the potential in drug discovery and are explored in various fields like pharmaceuticals, cosmetics, and agrochemicals. To minimize antimicrobial drug resistance, there is a need to design potent, safer antimicrobial lead compounds with higher selectivity and minimal cytotoxicity., Objectives: The present review aims to outline several recent developments in medicinal chemistry aspect of nitrogenous heterocyclic derivatives with the following purposes: (1) To cast light on the recent literature reports of the last eight years ranging from 2015 to 2023 describing anti-microbial potential of nitrogen-containing heterocyclic derivatives which includes pyrazole, pyrazoline, imidazole, tetrazole and quinoline; (2) To brief the recent developments in the medicinal chemistry of nitrogenous heterocyclic derivatives that is directed towards their anti-microbial profile; (3) To summarize the complete correlation of structural features of nitrogenous heterocyclic molecules with the pharmacological action including in silico as well as mechanistic studies to provide thoughts accompanying the generation of lead molecules., Methods: Antimicrobial potential of nitrogenous heterocyclic molecules has been displayed by relating the structural features of various lead candidates with their in vitro as well as in vivo antimicrobial outcomes. In contrast, in silico computational analysis from different articles also helped to predict the SAR of potent molecules., Results: Nitrogen containing heterocycles are involved in a range of natural to synthetic analogues with keen antimicrobial potency. It is an emerging need to generate new nitrogenous heterocyclic molecules in order to tackle the drug resistance in micro-organisms with more targeted selectivity as well as specificity., Conclusion: To limit the side effects associated with them and to combat the microbes acquired resistance towards the current drug regimen, novel nitrogenous heterocycle based antimicrobial agents are essential to be developed. This review connects the structural units present in lead compounds with their promising antimicrobial action., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Hyperuricemia is characterized by higher-than-normal levels of uric acid in the bloodstream. This condition can increase the likelihood of developing gout, a form of arthritis triggered by the deposition of urate crystals in the joints, leading to inflammation and pain. An essential part of purine metabolism is played by the enzyme xanthine oxidase (XO), which transforms xanthine and hypoxanthine into uric acid. Despite its vital role, diseases such as gout have been associated with elevated uric acid levels, which are linked to increased XO activity. To manage hyperuricemia, this study focuses on potential nitrogen based heterocyclic compounds that may serve as XO inhibitors which may lower uric acid levels and prevent hyperuricemia. Xanthine oxidase inhibitors are a class of medications used to treat conditions like gout by reducing the production of uric acid. The present study demonstrates numerous compounds, particularly nitrogen containing heterocyclic compounds including their synthesis, structure-activity relationship, and molecular docking studies. This paper also contains drugs undergoing clinical studies and the xanthine oxidase inhibitors that have been approved by the FDA., Competing Interests: There is no conflict of interest to declare., (This journal is © The Royal Society of Chemistry.)

Multidrug-resistant tuberculosis continues to pose a health security risk and remains a public health emergency. Antimicrobial resistance result from treatment regimens that are both insufficient and incomplete leading to the emergence of multidrug-resistant tuberculosis, extensively drug-resistant tuberculosis and totally drug-resistant tuberculosis. The impact of tuberculosis on the people suffering from HIV (Human immunodeficiency virus infection) have resulted in the increased research efforts in designing and discovery of novel antitubercular drugs that may result in decreasing treatment duration, minimising the need for multiple drug intake, minimising cytotoxicity and enhancing the mechanism of action of drug. While many drugs are available to treat tuberculosis, a precise and timely cure is still absent. Consequently, further investigation is needed to identify more recent molecular equivalents that have the potential to swiftly remove this disease. Isoniazid (INH), a treatment for tuberculosis (TB), targets the enzyme InhA (mycobacterium enoyl acyl carrier protein reductase), the Mycobacterium tuberculosis enoyl-acyl carrier protein (ACP) reductase, most common INH resistance is circumvented by InhA inhibitors that do not require KatG (catalase-peroxidase) activation, as a result, researchers are trying to work in the area of development of InhA inhibitors which could help in eradicating the era of tuberculosis from the world., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Alkaloids represent a wide class of naturally existing nitrogen-containing organic compounds having diverse biological activities. They are primary bioactive substances extracted from diverse plant parts. Due to their diverse biological activities, they are frequently used as medicines. The alkaloids have diverse pharmacological impacts on the human body; alkaloids are used for prevention, treatment, and reduction of discomfort associated with chronic illnesses. As most alkaloids exist in plants in complex form, combined with numerous other natural plant components, it is essential to recognize and characterize these molecules using different analytical techniques., Objectives: We aimed to review the literature on the methods and protocols for the analysis of naturally occurring alkaloids., Methods: We carried out a literature survey using the PubMed, Scopus, and Google Scholar databases and other relevant published materials. The keywords used in the searches were "alkaloids," "analytical methods," "HPLC method," "GC method," "electrochemical methods," and "bioanalytical methods," in various combinations., Results: In this article, several classes of alkaloids are presented, along with their biological activities. Moreover, it includes a thorough explanation of chromatographic techniques, hyphenated techniques, electrochemical techniques, and current trending analytical methods utilized for the isolation, identification, and comprehensive characterization of alkaloids., Conclusions: The various analytical techniques play an important role in the identification as well as the characterization of various alkaloids from plants, plasma samples, and urine samples. The hyphenation of various chromatographic techniques with mass spectrometry and NMR spectroscopy plays a crucial role in the characterization of unknown compounds., (© 2024 John Wiley & Sons Ltd.)

Arylpiperazine clubbed various heterocyclic molecules present potential pharmacophoric structural features for the development of psychoactive drugs. There are various CNS active molecules possessing arylpiperazine moiety in their pharmacophore approved by USFDA. In the current study, we have explored the benzhydrylpiperazine moiety clubbed with various substituted oxadiazole moieties (AP1-12) for their monoamine oxidase (MAO) inhibition and antidepressant potential. Compounds AP3 and AP12 exhibited highly potent and selective MAO-A inhibition with IC 50 values of 1.34 ± 0.93 µM and 1.13 ± 0.54 µM, respectively, and a selectivity index of 10- and 13-folds, respectively. Both the compounds displayed reversible binding character at the active site of MAO-A. In further in vivo evaluation, both the compounds AP3 and AP12 displayed potential antidepressant-like character in FST and TST studies via significantly reduced immobility time in comparison to non-treated animals. These compounds displayed no cytotoxicity in SH-SY5Y cell lines, which indicates that these compounds are safe for further evaluation. In silico studies reveal that synthesized compounds possess drug-likeness with minimal to no toxicity. In silico studies were conducted to understand the binding interactions and stability of compounds at the binding pocket of enzyme and observed that both the best compounds fit well at the active site of MAO-A lined by amino acid residues Tyr69, Asn181, Phe208, Ile335, Leu337, Phe352, and Tyr444 similar to standard MAO-A inhibitor clorgiline. The molecular dynamic studies demonstrated that AP3 and AP12 formed quite a stable complex at the active site of MAO-A and did not break under small abruption forces. The favourable binding interactions and appropriate ADMET properties present the benzhydrylpiperazine clubbed oxadiazole pharmacophoric features as a potential structural skeleton for further clinical evaluation and development of a new antidepressant drug molecule., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Purpose: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that primarily affects adults, characterized by muscle weakness resulting from the specific death of motor neurons in the spinal cord and brain. The pathogenesis of ALS is associated with the accumulation of mutant superoxide dismutase 1 (SOD1) proteins and neurofilaments in motor neurons, highlighting the critical need for disease-modifying treatments. Current therapies, such as riluzole and edaravone, provide only symptomatic relief. Recently, tofersen gained approval from the US FDA under the brand name Qalsody as the first and only gene therapy for ALS, addressing a significant pathological aspect of the disease., Methods: We carried out a literature survey using PubMed, Scopus, National Institutes of Health, and Biogen for articles published in the English language concerned with "amyotrophic lateral sclerosis", pathophysiology, current treatment, treatment under clinical trial, and the newly approved drug "tofersen" and its detailed summary., Results: A comprehensive review of the literature on the pathophysiology, available treatment, and newly approved drug for this condition revealed convincing evidence that we are now able to better monitor and treat ALS., Conclusions: Although treatment of ALS is difficult, the newly approved drug tofersen has emerged as a potential therapy to slow down the progression of ALS by targeting SOD1 mRNA, representing a significant advancement in the treatment of ALS., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Type 1 diabetes (T1D) is a chronic autoimmune disease caused by CD4+ and CD8+ that are activated via CD3+ cells and finally lead to the macrophages destroying the beta cells in the pancreas thereby causing diabetes. The anti-CD3 humanized monoclonal antibody was approved on 17th November 2022 by the United States Food Drug Administration (USFDA) with the name teplizumab and the brand name TZIELD. This is the only approved drug that treats type 1 diabetes (T1D) by delaying the onset of stage 3 in type 1 diabetes (T1D). This review outlines essential features of teplizumab including its brief introduction to its mechanism and other therapies for the treatment and various risks as well as the pharmacokinetics and pharmacodynamics of this disease and the clinical trial reports for the completed and ongoing therapies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

For proper functioning of the human body, several metals are required in different concentrations but if their concentration slightly elevates, because of any metal-contaminated environment or of other food sources, which leads to high toxicity and different chronic health issues. Different analytical techniques like atomic absorption spectroscopy, X-ray fluorescence, inductively coupled plasma- mass spectroscopy (ICP-MS) and flame atomic absorption spectroscopy are used for metals analysis present in different samples in different fields but nowadays neutron activation analysis (NAA) is preferred over other analytical techniques because it is an efficient, multi-elemental, nondestructive analytical technique having an ultralow minimum detection limit, therefore it can detect heavy metals (HMs) even if at a very trace level parts per billion (ppb) with a quite simple sample preparation technique. This technique is known as "referee technique" because of its accuracy and trustworthiness. There is a widespread use of this technique in biomedical science like in Alzheimer's disease, cancer, arthritis, metabolism study, brain tumor and in many more conditions where metals are actively present. For its typical sample sizes and due to a multitude of additional benefits, it also helps in mapping of pathophysiology of the disease. Besides all, mainly in biomedical science the biological samples can easily be analyzed irrespective of any form. In recent years NAA is preferred over other analytical techniques in several research fields, so this article focuses on the analytical technique, its general principle and recent applications.

Nutraceuticals are products that provide both nutritional and therapeutic benefits. These compounds can slow the aging process and provide physiological effects shielding individuals from acute and chronic diseases. People's interests have shifted from allopathic to Ayurvedic to nutraceuticals in recent years. These are often common dietary supplements that have drawn customers worldwide because of their high nutritional safety and lack of adverse effects when used for a long time. Although conventional dosage forms, including pills, tablets, and semi-solids, are still available, they nevertheless have poorer bioavailability, less stability, and less effectiveness for targeted delivery of bioactives. The use of effective nanocomplex systems as nano-antioxidants using nanotechnology has become a promising field. Among its many uses, nanotechnology is mostly used to create foods and nutraceuticals that are more bioavailable, less toxic, and more sustainable. Additionally, it has been emphasized how precisely nano-pharmaceuticals for oxidative stress produce the desired effects. These improvements show improved antioxidant delivery to the target region, reduced leakage, and increased targeting precision. The outcomes demonstrated that oxidative stress-related illnesses can be effectively treated by lowering ROS levels with the use of nanonutraceuticals. The major ideas and uses of nano-nutraceuticals for health are outlined in this review, with an emphasis on reducing oxidative stress., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Parkinson's disease (PD) is a devastating neurodegenerative condition that mostly damages dopaminergic neurons in the substantia nigra and impairs human motor function. Males are more likely than females to have PD. There are two main pathways associated with PD: one involves the misfolding of α-synuclein, which causes neurodegeneration, and the other is the catalytic oxidation of dopamine via MAO-B, which produces hydrogen peroxide that can cause mitochondrial damage. Parkin (PRKN), α- synuclein (SNCA), heat shock protein (HSP), and leucine-rich repeat kinase-2 (LRRK2) are some of the target areas for genetic alterations that cause neurodegeneration in Parkinson's disease (PD). Under the impact of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is also important in Parkinson's disease (PD), inhibition of mitochondrial complex 1 results in enhanced ROS generation in neuronal cells. Natural products are still a superior option in the age of synthetic pharmaceuticals because of their lower toxicity and moderate side effects. A promising treatment for PD has been discovered using betacarboline (also known as "β-carboline") and indole alkaloids. However, there are not many studies done on this particular topic. In the herbs containing β-carbolines and indoles, the secondary metabolites and alkaloids, β-carbolines and indoles, have shown neuroprotective and cognitive-enhancing properties. In this review, we have presented results from 18 years of research on the effects of indole and β-carboline alkaloids against oxidative stress and MAO inhibition, two key targets in PD. In the SAR analysis, the activity has been correlated with their unique structural characteristics. This study will undoubtedly aid researchers in looking for new PD treatment options., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Breast carcinoma is among the most frequent cancerous tumour in females around the globe. The major modalities now employed in the therapeutic management of breast cancer include surgeries, chemotherapy, and specialized medicines. Despite their potential to help individuals' problems, they are also associated with many negative impacts. As a result, natural products are increasingly regarded to be a preferable alternative. Alkaloids are essential biochemical substances that can be used to develop new drugs. Numerous alkaloids that originate from natural plants have been shown in vitro and in vivo to have anti-proliferation and anti-metastasis actions on different kinds of carcinoma. According to the data collected in this study, the utilization of alkaloids as anti-tumor medicines appears to be extremely potent; nevertheless, extensive studies and clinical trials are required before utilizing individual alkaloids. In this overview, we provide a detailed and vital exploration of pre-existing alkaloids possessing anti-tumor activities due to bioactive compounds. This study also includes an overview of synthesized analogues and pharmacological characteristics that will be beneficial to scientists working on alkaloids for medicinal purposes. In a recent survey of the literature, alkaloids are an important component of plantderived antitumor medicines that hold great potential for the future development of cancer therapy and preventive therapies. We have also discussed structural analysis relationship (SAR) studies. Moreover, it covers clinical trial medications and FDA-approved medicines from the last five years that will be useful in further research., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Embelin (EMB) (2,5-Dihydroxy-3-undecyl-1,4-benzoquinone) is a natural benzoquinone extracted mainly from Embelia ribes (ER) and appear as vivid orange dots beneath the fruit's pericarp. It is being used to treat various diseases since ancient times in India. It has been ascribed as one of the 32 ayurvedic drugs of national importance in the National Medicinal Plant Board set up by the Government of India under the Ministry of Indian System of Medicine and Homeopathy. Embelin prevents neuronal oxidative damage by decreasing the peroxidation of lipids. Along with having antioxidant properties, it also prevents the production of amyloid-protein-related fibrils and blocks the progression of inflammatory cascades. Due to embelin's ability to cross the blood-brain barrier, its neuroprotective effects have been studied in the past using in vitro models of neuronal disorders such as convulsion and epilepsy, Alzheimer's disease, anxiety and depression, traumatic brain injury, cerebral ischemia, Huntington's disease, and multiple sclerosis. In addition to its neuroprotective effects, its role as an antitubercular, anti-cancer, antioxidant, astringent, anti-inflammatory, anti-bacterial, contraceptive, carminative, diuretic, and anthelmintic agent has also been studied. With docking studies and recent advancements in formulations of embelin including polyethylene and embelin micelles and embelin noisome preparations, embelin can prove to be a promising compound for its therapeutic actions in a wide range of diseases and disorders. The findings of docking studies suggest the binding ability of embelin to be similar to the standard drug in their respective disorders. In this review and docking analysis, we bring an outline of scientific evidence concerning the neuroprotective actions of embelin, still, further research is required for its prospective as a chief compound in clinical approaches., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Neurodegenerative disorders (NDDs) are multifaceted complex disorders that have put a great health and economic burden around the globe nowadays. The multi-factorial nature of NDDs has presented a great challenge in drug discovery and continuous efforts are in progress in search of suitable therapeutic candidates. Nature has a great wealth of active principles in its lap that has cured the human population since ancient times. Natural products have revealed several benefits over conventional synthetic medications and scientists have shifted their vision towards exploring the therapeutic potentials of natural products in the past few years. The structural mimicking of natural compounds to endogenous ligands has presented them as a potential therapeutic candidate to prevent the development of NDDs. In the presented review, authors have summarized demographical facts about various NDDs including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and various types of sclerosis in the brain. The significant findings of new active principles of natural origin along with their therapeutic potentials on NDDs have been included. Also, a description of clinical trials and patents on natural products has been enlisted in this compilation. Although natural products have shown promising success in drug discovery against NDDs, still their use is associated with several ethical issues which need to be solved in the upcoming time., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Erratic cell proliferation is the initial symptom of cancer, which can eventually metastasize to other organs. Before cancer becomes metastatic, its spread is triggered by pro-angiogenic factors including vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), Platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR) and Platelet Factor (PF4), all of which are part of receptor tyrosine kinase (RTK) family. Receptor tyrosine kinases (RTKs) are cell-surface proteins and aresignaling enzymes that transfer ATP-phosphate to tyrosine residue substrates. Important biological processes like proliferation, differentiation, motility, and cell-cycle regulation are all possessedby these proteins. Unusual RTK expression is typically associated with cell growth abnormalities, which is linked to tumor acquisition, angiogenesis, and cancer progression. In addition to the already available medications, numerous other heterocyclic are being studied for their potential action against a variety of cancers. In the fight against cancer, in particular, these heterocycles have been used for their dynamic core scaffold and their inherent adaptability. In this review article, we have compiled last five years research work including nitrogen containing heterocycles that have targeted RTK. Herein, the SAR and activity of various compounds containing diverse heterocyclic (pyrimidine, indole, pyridine, pyrazole, benzimidazole, and pyrrole) scaffolds are discussed, and they may prove useful in the future for designing new leads against RTKs. Our focus in this manuscript is to comprehensively review the latest research on the biological activity and structural activity relationship of nitrogen compounds as RTK inhibitors. We believe that this may be an important contribution to the field, as it can help guide future research efforts and facilitate the development of more effective cancer therapies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The sodium dependent SLC13 family transporters comprise of five genes SLC13A1, SLC13A2 (NaDC1), SLC13A3 (NaDC3), SLC13A4 and SLC13A5 (NaCT). Among them, NaDC1, NaDC3 and NaCT are sodium dependent transporters belonging to family of dicarboxylates (succinate, malate, α-ketoglutarate) and tricarboxylates (citrate). The mouse and the human NaCT structures have still not been crystallized, therefore structural information is taken from the related bacterial transporter of VcINDY. Citrate in the cytosol works as a precursor for the fatty acid synthesis, cholesterol, and low-density lipoproteins. The excess citrate from the matrix is translocated to the cytosol for fatty acid synthesis through these transporters and thus controls the energy balance by downregulating the glycolysis, tricarboxylic acid (TCA), and fatty acid breakdown. These transporters play an important role in regulating various metabolic diseases including cancer, diabetes, obesity, fatty liver diseases and CNS disorders. These di and tricarboxylate transporters are emerging as new targets for metabolic disorders such as obesity and diabetes. The mutation in the function of the NaCT causes several neurological diseases including neonatal epilepsy and impaired brain development whereas mutation of genes coding for citrate transport present in the liver may provide positive effect. Therefore, continued efforts from the earlier work on citrate transporters are required for the development of citrate inhibitors. This review discusses the structure, function, and regulation of the NaCT transporter. The review also highlights citrate role in diagnosing diseases such as cancer, diabetes, fatty liver, and diabetes. The therapeutic perspective of synthetic inhibitors against NaCT transporters is succinctly summarized., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Terpenes and terpenoids are the primary bioactive substances present in essential volatile oils, condensed liquids extracted from diverse plant parts. These substances demonstrate remarkable biological activity and are frequently used as medicines, food additives, and scent molecules. Terpenoids have a wide range of pharmacological effects on the human body, including the treatment, prevent, and reduce the discomfort associated with a number of chronic illnesses. Therefore, these bioactive substances are crucial to our everyday existence. As most terpenoids are present in complex form, coupled with many other raw plant elements, it is important to identify and characterize these molecules. This article addresses various classes of terpenoids, their biochemical processes, and their biological functions. Additionally, it includes a comprehensive description of several hyphenated procedures and recently popular analytical approaches used for isolation, identification, and absolute characterization. It also includes a discussion of the various advantages, drawbacks, and challenges encountered during the collection of the sample and throughout the entire research process.

Rhodanine or 2-Thioxothiazolidin-4-one is a privileged heterocyclic compound offering a wide opportunity for structural modification, lead development, and modification. It is one of the highly decorated scaffolds in the drug discovery process. Rhodanine derivatives possess a plethora of biological activities due to their ability to interact with a diverse range of protein targets, which provide tremendous opportunities to discover new drugs with different modes of action. The most common strategy for developing novel rhodanine derivatives is the introduction of structurally diverse substituents at the C-5 or N-3, or both positions. Since the inception of Epralestat into the market in 1992, the exploration of rhodanine-3-acetic acids has led to the development of novel leads against different biological targets such as MRSA, HHV-6, Mycobacterial tuberculosis, dengue, etc. In the current pandemic era, some rhodanine compounds have been explored against SARS-CoV-2. In recent years, rhodanine and its derivatives have witnessed significant progress in developing new drug leads as potential antimicrobial and antiviral agents. Different synthetic methodologies and recent developments in the medicinal chemistry of rhodanine derivatives, including biological activities, their mechanistic aspects, structure-activity relationships, and in silico findings, have been compiled in the present review. This article will benefit the scientific community and offer perspectives on how these scaffolds as privileged structures might be exploited in the future for rational design and discovery of rhodanine-based bio-active molecules., (© 2022 John Wiley & Sons Ltd.)

The novel series of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides (R: 1-12) were designed, synthesized and evaluated for in-vitro and in-vivo antidepressant-like activity. In MAO-A inhibition assay, compound R: 5 and R: 9 displayed most potent activity with IC 50  = 0.12 and 0.30 µM. R: 5 and R: 9 were also evaluated for in-vivo antidepressant using FST and TST. In both models, the test samples R: 5 and R: 9 showed noteworthy antidepressant effect. R: 5 showed 46.48 % and 45.96 % reduction in immobility in FST and TST respectively at dosage of 30 mg/kg (p.o). Whereas compound R: 9 reduced the immobility time by 52.76 % and 47.14 % as compared to control in FST and TST, respectively at same dosage. Both the compounds were also tested for behavioural study using actophotometer and grip tests. None of compounds exhibited decrease in locomotor activity. Further, these compounds were subjected to in silico studies to determine their ADME properties along with binding energies and binding orientions. In ADME studies none of the compounds violated the Lipinski rule and all other parameters were also within the acceptable ranges. In docking study R: 5 (-10.7) and R: 9 (-10.4) were also displayed highest docking score. These encouraging results present the pharmacophoric features of substituted-N-(5,6-diphenyl-1,2,4-triazin-3-yl) benzamides as interesting lead for further development of new antidepressant drug molecules., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Most of the new drug candidates and present ones are lipophilic, which leads to low bioavailability. Self-emulsifying drug delivery systems (SEDDS) have emerged as promising formulation system for poorly water-soluble drug candidates. Over the last two decades, various such drug compounds were used by researchers for the development of SEDDS. At present, many SEDDS formulations are also available in the market. Though SEDDS offer many advantages but drawbacks like low drug loading, few dosage form choices, difficulty in handling and storage led to the solidification of this system by various methods. Solidification by spray drying technique offers a lot of advantages like scalability and stability. This particular method is the focus of this review. Adsorbent carriers have the most significant role in the fate of this formulation and its compatibility with the drug candidate. This review addresses the advantages, method of development, spray drying specifications, and characterization of S-SEDDS in detail. Furthermore, the prospect of turning spray-dried SEDDS into tablets by punching which offers potential advantages of increased bioavailability and stability has also been discussed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The synthesis of biogenic nanoparticles from readily available natural resources may have large demand in numerous fields including pharmaceuticals and medicine. The biogenic nanoparticles catch the attention of the scientific community due to their low cytotoxicity and biocompatibility. Chemical, physical, and greener methods are used for the synthesis of biogenic nanoparticles. Researchers used eco-friendly and nontoxic approaches in the synthesis of this nanoparticle. This nanomaterial-based medicine plays a vital role in the management of public health, including earlier detection of disease, therapeutics candidates in the treatment of cancer. Biogenic nanocomposites are environmentally benign candidates that include fabrication of various composites, detoxification, and act as a catalyst in the biodegradation process. In this review article, we emphasize the recently reported methods used for synthesis, summarizing their biomedical applications and commercial and environmentally benign applications. Synthetic strategies include greener, chemical, physical, and biogenic methods and their role in surface modifiers involves various biomedical, commercial, and environmental-related applications. Moreover, we glimpse existing status, key contests, and future perspectives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Tuberculosis (TB) is an airborne infection caused by the bacteria Mycobacterium Tuberculosis (MTB). It mainly affects the lungs and causes severe coughing, fever, and chest pains. With the rising prevalence of drug-resistant and inactive Tuberculosis (TB), there is an essential need to discover more effective molecules capable of combating this heinous illness. Pyrazinamide is a first-line tuberculosis therapy that shortens prophylactic duration from twelve to six months. The majority of presently used tuberculosis medications were found by a mix of serendipity and innovative chemical alterations of an existing lead drug. Given that the majority of these discoveries occurred years ago, there is a definite need to use fresh methodologies and technology for discovery to meet the grave danger posed by tuberculosis and the rise of treatment resistance strains. Although current research has provided significant insight into TB transmission, diagnosis, and treatment in the last four years, much more progress is needed to successfully reduce tuberculosis prevalence and eventually eradicate it. The disease continues to be a public health concern, second only to HIV/AIDS in high fatality rates. This review focuses on current efforts to translate the anti-tubercular activity of all known pyrazinamide analogues and proposes a novel approach for developing new anti-tubercular drugs based on the fusion of pyrazinamide with various heterocyclic rings that shorten treatment for drug-sensitive and multidrug-resistant tuberculosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Iridoids are secondary plant metabolites that are multitarget compounds active against various diseases. Iridoids are structurally classified into iridoid glycosides and non-glycosidic iridoids according to the presence or absence of intramolecular glycosidic bonds; additionally, iridoid glycosides can be further subdivided into carbocyclic iridoids and secoiridoids. These monoterpenoids belong to the cyclopentan[c]-pyran system, which has a wide range of biological activities, including antiviral, anticancer, antiplasmodial, neuroprotective, anti-thrombolytic, antitrypanosomal, antidiabetic, hepatoprotective, anti-oxidant, antihyperlipidemic and anti-inflammatory properties. The basic chemical structure of iridoids in plants (the iridoid ring scaffold) is biosynthesized in plants by the enzyme iridoid synthase using 8-oxogeranial as a substrate. With advances in phytochemical research, many iridoid compounds with novel structure and outstanding activity have been identified in recent years. Biologically active iridoid derivatives have been found in a variety of plant families, including Plantaginaceae, Rubiaceae, Verbenaceae, and Scrophulariaceae. Iridoids have the potential of modulating many biological events in various diseases. This review highlights the multitarget potential of iridoids and includes a compilation of recent publications on the pharmacology of iridoids. Several in vitro and in vivo models used, along with the results, are also included in the paper. This paper's systematic summary was created by searching for relevant iridoid material on websites such as Google Scholar, PubMed, SciFinder Scholar, Science Direct, and others. The compilation will provide the researchers with a thorough understanding of iridoid and its congeners, which will further help in designing a large number of potential compounds with a strong impact on curing various diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's disease (AD) remains one of the major neurodegenerative diseases overwhelming the world today. Alzheimer's is the most complicated as well as perplexing disease encountering serious global health issues. Alzheimer's disease is well characterized as a general cause of dementia, which includes issues with memory, language, problem-solving, and other cognitive behaviours, such as disabled perception as well as trouble talking due to degeneration of neurons. According to the latest report, there are about 44 million individuals who are currently suffering from dementia, which has been prophesied to extensively grow up to 3-fold by 2050. Alzheimer's disease is usually triggered by numerous associated factors, including depleted amount of acetylcholine (ACh), excessive aggregation of β-amyloid peptide (Aβ), tau hyperphosphorylation with neurofibrillary tangle formation as well as deposition of feeble plaques in a specific portion of the brain (hippocampus and cortex). Besides these superior factors, sometimes AD can be induced or become complex due to several reasons, such as inflammatory mechanisms and oxidative stress. Furthermore, heterocyclic scaffolds comprise assorted implications in the drug design and development process. Heterocycles have also elicited their evolving role as core scaffolds in numerous synthetic derivatives with potent anti-Alzheimer's potential. There are only limited drugs that are present in the market to treat Alzheimer's disease in an efficacious manner. Hence, the identification, design, and development of new anti-Alzheimer's drugs are an emerging need to eradicate complex clinical indications associated with Alzheimer's disease. This review aims to summarize various recent advancements in the medicinal chemistry of heterocycle-based compounds with the following objectives: (1) to represent inclusive literature reports describing the anti-Alzheimer's potential of heterocyclic derivatives; (2) to cast light on recent advancements in the medicinal chemistry of heterocyclic compounds endowed with therapeutic potential against Alzheimer's disease; (3) to summarize the comprehensive correlation of structure-activity relationship (SAR) with the pharmacological responses, including in silico and mechanistic studies to provide ideas related to design and development of lead molecules., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Renal cell carcinoma (RCC) is a diverse collection of malignancies with varying histological characteristics, molecular changes, prognosis, and therapeutic response. Tivozanib was first approved in March 2021 by USFDA with the brand name Fotivda. Tivozanib hydrochloride monohydrate is an oral medication that is used to treat relapsed or refractory renal cell carcinoma., Objective: In this review, we explain renal cell carcinoma and its different types of treatment by the anti-renal carcinoma drugs., Methods: A comprehensive literature search was conducted in the relevant databases, like ScienceDirect, PubMed, ResearchGate, and Google Scholar, to identify the studies., Conclusion: Tivozanib is an oral VEGFR-1, VEGFR-2, and VEGFR-3 tyrosine kinase inhibitor that is extremely selective and powerful. It has much less affinity for other receptor tyrosine kinases than multi-targeted TKIs now in clinical use. Because of its long half-life in circulation, it may be able to block VEGFRs more consistently. Doserelated controllable hypertension is its most commonly seen drug-related side event. Fatigue, hoarseness, and diarrhea, which are all common side effects, are not dose-related. Because of its target specificity, tivozanib can work well with other medications that have low side effects. Blocking both the VEGF and mTOR signaling pathways at the same time provides the benefit of synergistic antitumor efficacy while also preventing treatment resistance. Thus, overall we can say that the drug tivozanib is suitable for treatment in patients with renal cell carcinoma and can be investigated in multi-center clinical trials., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Amivantamab was approved on May 21st, 2021, by United States food and drug administration with the brand name Rybervant, used particularly for adult patients with exon20 insertion of epithelial growth factor receptor with locally advanced metastatic non-small cell lung cancer., Objective: In this review, we explain the non-small cell lung cancer and molecular distinctions between non-small cell lung cancer and small cell lung cancer. We also conclude numerous components of non-small cell lung cancer, which include signs and symptoms of Amivantamab in inhibiting the cancer cell growth, various clinical trials on Amivantamab, adverse effects, and the contraindications of Amivantamab., Methods: A comprehensive literature search was conducted in the relevant databases like ScienceDirect, PubMed, ResearchGate, and Google Scholar to identify studies., Conclusion: Amivantamab is a new bispecific antibody that targets non-small cell lung cancer through two different pathways, i.e., by binding to epithelial growth factor receptor and mesenchymal epithelial transition factor. Amivantamab gets tightly bound to Fcγ3R, and thus, mediates the macrophage and NK-cell for the killing of cancer cells. Biological treatment of Amivantamab shows effectiveness against the epithelial growth factor receptor Exon20 insertions according to the preclinical data of the animal model., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure-activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.

Cancer is the most lethal disease that may be found anywhere globally. Approximately 10% of individuals die due to cancer of various types, with 19.3 million new cancer cases and 10 million deaths reported in 2020. More than 100 medications are commercially available for the treatment of cancer, but only a few candidates have high specificity, resulting in several side effects. The scientific community has spent the past decades focusing on drug discovery. Natural resources are used to isolate pharmaceutically active candidates, which are then synthesized in laboratories. More than 60% of all prescribed drugs are made from natural ingredients. Unique five-membered heteroaromatic center motifs with sulfur, oxygen and nitrogen atoms are found in heterocyclic compounds, such as indazole, thiazole, triazole, triazole, and oxazole, and are used as a core scaffold in many medicinally important therapies. Triazole possesses a wide range of pharmacological activities, including anticancer, antibacterial, antifungal, antibiotic, antiviral, analgesic, anti-inflammatory, anti-HIV, antidiabetic, and antiprotozoal activities. Novel triazole motifs with a variety of biological characteristics have been successfully synthesized using versatile synthetic methods. We intend here to facilitate the rational design and development of innovative triazole-based anti-cancer medicines with increased selectivity for various cancer cell lines by providing insight into various ligand-receptor interactions., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is associated with a comprehensive burden that significantly affects patient's quality of life. Even though patients' disease condition is improving following conventional therapies, researchers are studying alternative tools that can penetrate solid tumours to deliver the therapeutics due to issues of developing resistance by the cancer cells. Treating cancer is not the only the goal in cancer therapy; it also includes protecting non-cancerous cells from the toxic effects of anti-cancer agents. Thus, various advanced techniques, such as cell-based drug delivery, bacteria-mediated therapy, and nanoparticles, are devised for site-specific delivery of drugs. One of the novel methods that can be targeted to deliver anti-cancer agents is by utilising genetically modified non-pathogenic bacterial species. This is due to the ability of bacterial species to multiply selectively or non-selectively on tumour cells, resulting in biofilms that leads to disruption of metastasis process. In preclinical studies, this technology has shown significant results in terms of efficacy, and some are currently under investigation. Therefore, researchers have conducted studies on bacteria transporting the anti-cancer drug to targeted tumours. Alternatively, bacterial ghosts and bacterial spores are utilised to deliver anti-cancer drugs. Although in vivo studies of bacteria-mediated cancer therapy have shown successful outcome, further research on bacteria, specifically their targeting mechanism, is required to establish a complete clinical approach in cancer treatment. This review has focused on the up-to-date understanding of bacteria as a therapeutic carrier in the treatment of cancer as an emerging field., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Breast cancer (BC)-related mortality primarily results from metastatic colonization of disseminated cells. Actin polymerization plays an important role in driving post-extravasation metastatic outgrowth of tumor cells. This study examines the role of myocardin-related transcription factor (MRTF)/serum-response (SRF), a transcription system well known for regulation of cytoskeletal genes, in metastatic colonization of BC cells. We demonstrated that co-depletion of MRTF isoforms (MRTF-A and MRTF-B) dramatically impairs single-cell outgrowth ability of BC cells as well as retards growth progression of pre-established BC cell colonies in three-dimensional (3D) cultures. Conversely, overexpression of MRTF-A promotes initiation and progression of tumor-cell outgrowth in vitro , primary tumor formation, and metastatic outgrowth of seeded BC cells in vivo , and these changes can be dramatically blocked by molecular disruption of MRTF-A's interaction with SRF. Correlated with the outgrowth phenotypes, we further demonstrate MRTF's ability to augment the intrinsic cellular ability to polymerize actin and formation of F-actin-based protrusive structures requiring SRF's interaction. Pharmacological proof-of-concept studies show that small molecules capable of interfering with MRTF/SRF signaling robustly suppresses single-cell outgrowth and progression of pre-established outgrowth of BC cells in vitro as well as experimental metastatic burden of BC cells in vivo. Based on these data, we conclude that MRTF activity potentiates metastatic colonization of BC cells and therefore, targeting MRTF may be a promising strategy to diminish metastatic burden in BC., Competing Interests: The authors declare that the authors have no conflict of interest with the content of the article., (© 2022 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology.)

Traumatic brain injury (TBI) is a neurological disorder which represents a major health issue worldwide. It causes mortality and disability among all group ages, caused by external force, sports-related events or violence and road traffic accidents. In the USA, approximately one-third people die annually due to injury and 1.7 million people suffer from traumatic brain injury. Every year in India around 1.6 million individuals suffer from sustain brain injury with 200,000 deaths and approximately one million person needed recovery treatment at any stage of time. Sports-related head impact and trauma has become an extremely controversial public health and medico-legal problem that accounts for 20% of all brain injury (including concussion). It is difficult to reverse the primary injury but the secondary injury can be minimized by using proper pharmacological intervention during the initial hours of injury. This article highlights the pathophysiology and types of TBI along with treatment therapies. Till date, there is no single medication that can decrease the progression of the disease so that symptomatic treatment is given to the patient by determining proper pathology. Recently various herbal medicine therapies and traditional supplements have been developed for TBI. Nutritional supplementation and nutraceuticals have exposed potential in the treatment of TBI when used before and after TBI. The compiled data will enable the readers to know the pathophysiology as well as the allopathic and natural remedies to treat the TBI., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cancer can be considered as a genetic as well as a metabolic disorder. The current cancer treatment scenario looks like aggravating tumor cell metabolism, causing the disease to progress even with greater intensity. The cancer therapy is restricted to the limitations of poor patient compliance due to toxicities to normal tissues and multi-drug resistance development. There is an emerging need for cancer therapy to be more focused towards better understanding of genetic, epigenetic and transcriptional changes resulting in cancer progression and their relationship with treatment sensitivity., Objective: The 4-thiazolidinone nucleus possesses marked anticancer potential towards different biotargets, thus targeting different cancer types like breast, prostate, lung, colorectal and colon cancers, renal cell adenocarcinomas and gliomas. Therefore, conjugating the 4-thiazolidinone scaffold with other promising moieties or directing the therapy towards targeted drug delivery systems like the use of nanocarrier systems, can provide the gateway for optimizing the anticancer efficiency and minimizing the adverse effects and drug resistance development, thus providing stimulus for personalized pharmacotherapy., Methods: An exhaustive literature survey has been done to give an insight into the anticancer potential of the 4- thiazolidinone nucleus either alone or in conjugation with other active moieties, with the mechanisms involved in preventing proliferation and metastasis of cancer covering a vast range of publications of repute., Conclusion: This review aims to summarise the work reported on anticancer activity of 4-thiazolidinone derivatives covering various cancer biomarkers and pathways involved, citing the data from the year 2005 till now, which may be beneficial to the researchers for future development of more efficient 4-thiazolidinone derivatives., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: This paper aims to describe the structure activity relationship of heterocyclic derivatives with multi-targeted anticancer activity., Objectives: With the following goals in mind, this review tries to describe significant recent advances in the medicinal chemistry of heterocycle-based compounds: (1) To shed light on recent literature focused on heterocyclic derivatives' anticancer potential; (2) To discuss recent advances in the medicinal chemistry of heterocyclic derivatives, as well as their biological implications for cancer eradication; (3) To summarise the comprehensive correlation of structure activity relationship (SAR) with pharmacological outcomes in cancer therapy., Background: Cancer remains one of the major serious health issues in the world today. Cancer is a complex disease in which improperly altered cells proliferate at an uncontrolled, rapid, and severe rate. Variables such as poor dietary habits, high stress, age, and smoking, can all contribute to the development of cancer. Cancer can affect almost any organ or tissue, although the brain, breast, liver, and colon are the most frequently affected organs. For several years, surgical operations and irradiation have been in use along with chemotherapy as a primary treatment of cancer, but still, effective treatment of cancer remains a huge challenge. Chemotherapy is now considered one of the most effective strategies to eradicate cancer, although it has been shown to have a number of cytotoxic and unfavourable effects on normal cells. Despite all of these cancer treatments, there are several other targets for anticancer drugs. Cancer can be effectively eradicated by focusing on these targets, including cell-specific and receptor-specific targets such as tyrosine kinase receptors (TKIs). Heterocyclic scaffolds also have a variety of applications in drug development and are a common moiety in the pharmaceutical, agrochemical, and textile industries., Methods: The association between structural activity relationship data of many powerful compounds and their anticancer potential in vitro and in vivo has been studied. SAR of powerful heterocyclic compounds can also be generated using molecular docking simulations, as reported in literature., Conclusion: Heterocycles have a wide range of applications, from natural compounds to synthesised derivatives with powerful anticancer properties. To avoid cytotoxicity or unfavourable effects on normal mammalian cells due to a lack of selectivity towards the target site, as well as to reduce the occurrence of drug resistance, safer anticancer lead compounds with higher potency and lower cytotoxicity are needed. This review emphasizes on design and development of heterocyclic lead compounds with promising anticancer potential., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Today, antibacterial drug resistance has turned into a significant public health issue. Repeated intake, suboptimal and/or unnecessary use of antibiotics, and, additionally, the transfer of resistance genes are the critical elements that make microorganisms resistant to conventional antibiotics. A substantial number of antibacterials that were successfully utilized earlier for prophylaxis and therapeutic purposes have been rendered inadequate due to this phenomenon. Therefore, the exploration of new molecules has become a continuous endeavour. Many such molecules are at various stages of the investigation. A surprisingly high number of new molecules are currently in the stage of phase 3 clinical trials. A few new agents have been commercialized in the last decade. These include solithromycin, plazomicin, lefamulin, omadacycline, eravacycline, delafloxacin, zabofloxacin, finafloxacin, nemonoxacin, gepotidacin, zoliflodacin, cefiderocol, BAL30072, avycaz, zerbaxa, vabomere, relebactam, tedizolid, cadazolid, sutezolid, triclosan, and afabiacin. This article aims to review the investigational and recently approved antibacterials with a focus on their structure, mechanisms of action/resistance, and spectrum of activity. Delving deep, their success or otherwise in various phases of clinical trials is also discussed while attributing the same to various causal factors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Neurodegenerative disorders belong to different classes of progressive/ chronic conditions that affect the peripheral/central nervous system. It has been shown through studies that athletes who play sports involving repeated head trauma and sub-concussive impacts are more likely to experience neurological impairments and neurodegenerative disorders in the long run Aims: The aim of the current narrative review article is to provide a summary of various nutraceuticals that offer promise in the prevention or management of sports-related injuries, especially concussions and mild traumatic brain injuries., Methods: This article reviews the various potential nutraceutical agents and their possible mechanisms in providing a beneficial effect in the injury recovery process. A thorough survey of the literature was carried out in the relevant databases to identify studies published in recent years. In the present article, we have also highlighted the major neurological disorders along with the associated nutraceutical(s) therapy in the management of disorders., Results: The exact pathological mechanism behind neurodegenerative conditions is complex as well as idiopathic. However, mitochondrial dysfunction, oxidative stress as well as intracellular calcium overload are some common reasons responsible for the progression of these neurodegenerative disorders. Owing to the multifaceted effects of nutraceuticals (complementary medicine), these supplements have gained importance as neuroprotective. These diet-based approaches inhibit different pathways in a physiological manner without eliciting adverse effects. Food habits and lifestyle of an individual also affect neurodegeneration., Conclusion: Studies have shown nutraceuticals (such as resveratrol, omega-3-fatty acids) to be efficacious in terms of their neuroprotection against several neurodegenerative disorders and to be used as supplements in the management of traumatic brain injuries. Protection prior to injuries is needed since concussions or sub-concussive impacts may trigger several pathophysiological responses or cascades that can lead to long-term complications associated with CNS. Thus, the use of nutraceuticals as prophylactic treatment for neurological interventions has been proposed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

As a source of therapeutic agents, heterocyclic nitrogen-containing compounds and their derivatives are still interesting and essential. Pyrazole, a five-member heteroaromatic ring with two nitrogen atoms, has a major impact in chemical industries as well as pharmaceutical industries. Due to its wide range of biological activities against various diseases, it has been identified as a biologically important heterocyclic scaffold. The treatment of neurological disorders has always been a difficult task in both the past and present. Therefore, identifying therapeutically effective molecules for neurological conditions remains an open challenge in biomedical research and development. For developing novel entities as neuroprotective agents, recently, pyrazole scaffold has attracted medicinal chemists worldwide. The major focus of research in this area is discovering novel molecules as neuroprotective agents with minimal adverse effects and better effectiveness in improving the neurological condition. This review mainly covers recent developments in the neuropharmacological role of pyrazole incorporated compounds, including their structural-activity relationship (SAR), which also further includes IC 50 values (in mM as well as in μM), recent patents, and a brief history as neuroprotective agents., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Heterocyclic compounds offer an enormous area for new lead molecules for drug discovery. Till today, efforts are being continuously made to find appropriate treatment for the management of the deadly disease of cancer. Amongst the large number of heterocycles that are found in nature, heterocycles having oxygen obtained noteworthy attention due to their distinctive and pharmacological activities.'Pyran' is one of the most significant non-aromatic, sixmembered ring composed of one oxygen atom and five carbon atoms. It is considered a privileged structure since pyran and its related derivatives exhibit a wide spectrum of biological activities. Pyran derivatives are found to have excellent anti-cancer properties against various types of cancer. The present review focussed on the current advances in different types of pyran-based derivatives as anti-cancer agents. Various in vitro (cell based testing), in vivo (animal based testing) models as well as molecular docking along with results are also covered. A subsection describing briefly natural pyran containing anticancer compounds is also incorporated in the review., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The platinum (II) complexes as anticancer agents have been well explored for the development of novel analogs. Yet, none of them achieved clinical importance in oncology. At present, anticancer compounds containing platinum (II) complexes have been employed in the treatment of colorectal, lung, and genitourinary tumors. Among the platinum-based anticancer drugs, Cisplatin (cis-diamine dichloroplatinum (II), cis-[Pt(NH3)2Cl2]) is one of the most potent components of cancer chemotherapy. The nephrotoxicity, neurotoxicity and ototoxicity, and platinum compounds associated resistant cancer are some major disadvantages., Objective: With the rapidly growing interest in platinum (II) complexes in tumor chemotherapy, researchers have synthesized many new platinum analogs as anticancer agents that show better cytotoxicity, and less off-target effects with less cellular resistance. This follows the introduction of oxaliplatin, water-soluble carboplatin, multinuclear platinum and newly synthesized complexes, etc. Methods: This review emphasizes recent advancements in drug design and development, the mechanism of platinum (II) complexes, their stereochemistry, current updates, and biomedical applications of platinum-based anticancer agents., Conclusion: In the last few decades, the popularity of platinum complexes as potent anti-cancer agents has risen as scientists have synthesized many new platinum complexes that exhibit better cytotoxicity coupled with less off-target effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Prostate cancer is considered the second most diagnosed cancer, and one of the most common causes of death from cancer in men. Apalutamide is an effective, safe, and well-tolerated agent used for the treatment of men with non-metastatic Castration-Resistant Prostate Cancer (nmCRPC) and metastatic Hormone-Naive Prostate Cancer (mHNPC). Androgen receptor signaling is a leading factor that drives these prostate tumors. USFDA has approved apalutamide on 14 February 2018 as an agent that targets androgen receptor signaling through inhibition causing significant improvement in metastasis-free survival in patients with prostate cancer., Objective: In this review, various aspects related to apalutamide have been summarized which involve the mechanism of action, chemistry, synthesis, pharmacokinetics, pharmacodynamics, adverse reactions, and safety parameters., Methods: The literature was thoroughly searched in the relevant databases to identify studies published in this field during recent years. Special attention has been given to apalutamide clinical trials phases and its promising future as one of the first-line agents for the treatment of patients with advanced prostate cancer., Results: Ongoing trials are progressing for apalutamide monotherapy and also for its combinations in other disease settings. The expected results of such trials will shape the future scenario of prostate cancer therapy., Conclusion: This review article has highlighted different aspects of Apalutamide like its mechanism of action, adverse effects, pharmacokinetics, pharmacodynamics, clinical trials among others. The contents of this article should make an excellent read for prospective researchers in this field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)