An Insight into Cubosomal Drug Delivery Approaches: An Explicative Review.

Cubosomes, a novel drug delivery system, have gained significant attention in recent years due to their unique self-assembled structures and enhanced drug encapsulation capabilities. They are administered by oral, ophthalmic, transdermal, and chemotherapeutic routes, to name a few. Due to their many potential benefits-which include high drug dispersal due to the cubic structure, a large surface area, a relatively simple manufacturing process, biodegradability, the capacity to encapsulate hydrophobic, hydrophilic, and amphiphilic compounds, targeted and controlled release of bioactive agents, and the biodegradability of lipids-cubosomes show enormous promise in drug nanoformulations for cancer therapeutics. The most common preparation method involves emulsifying a monoglyceride with a polymer, homogenizing, and then sonicating the mixture. Two distinct approaches to preparing are top-down and bottom-up. This evaluation will examine the materials, methods of preparation, cubosome-related drug encapsulating techniques, drug loading, release mechanism, and their uses. The following databases were used for literature searches: PubMed, Frontiers, Science Direct, Springer, Wiley, and MDPI. For the purpose of finding pertinent articles and contents (2015-2024), the keywords "cubosome; drug delivery systems, nano-carrier, theranostic, drug release mechanism" and others of a similar nature were utilized. This review will conduct a comprehensive analysis of the cubosome-related composition, production methods, drug encapsulating strategies, drug release mechanisms, and applications. Moreover, the difficulties encountered in fine-tuning different parameters to improve loading capabilities and prospects are also discussed. Innovation in pharmaceutical research and development can be stimulated by the knowledge gathered about cubosomal drug delivery methods. Through the clarification of the mechanisms involved in drug release from cubosomes and the investigation of innovative fabrication procedures, scientists can enhance the cubosomal formulation design for targeted therapeutic uses.

Fyn Kinase in Alzheimer's Disease: Unraveling Molecular Mechanisms and Therapeutic Implications.

Alzheimer's disease, characterized by the accumulation of abnormal protein aggregates and neuronal damage in the brain, leads to a gradual decline in cognitive function and memory. As a complex neurodegenerative disorder, it involves disruptions in various biochemical pathways and neurotransmitter systems, contributing to the progressive loss of neurons and synaptic connections. The complexity of Alzheimer's signaling pathways complicates treatment, presenting a formidable challenge in the quest for effective therapeutic interventions. A member of the Src family of kinases (SFKs), Fyn, is a type of non-receptor tyrosine kinase that has been linked to multiple essential CNS processes, such as myelination and synaptic transmission. Fyn is an appealing target for AD treatments because it is uniquely linked to the two major pathologies in AD by its interaction with tau, in addition to being activated by amyloid-beta (Aß) through PrPC. Fyn mediates neurotoxicity and synaptic impairments caused by Aß and is involved in regulating the process of Aß synthesis.Additionally, the tau protein's tyrosine phosphorylation is induced by Fyn. Fyn is also a challenging target because of its widespread body expression and strong homology with other kinases of the Src family, which could cause unintentional off-target effects. This review emphasizes signaling pathways mediated by Fyn that govern neuronal development and plasticity while also summarizing the most noteworthy recent research relevant to Fyn kinase's function in the brain. Additionally, the therapeutic inhibition of Fyn kinase has been discussed, with a focus on the Fyn kinase inhibitors that are in clinical trials, which presents a fascinating opportunity for targeting Fyn kinase in the creation of possible therapeutic approaches for the management of Alzheimer's disease.

Smart Multifunctional Nanoparticles in Cancer Theranostics: Progress and Prospect.

BACKGROUND: Worldwide, cancer is the second most common cause of death. Chemotherapy and other traditional cancer treatments have toxicities that affect normal cells in addition to their intended targets, necessitating the development of novel approaches to enhance cell-specific targeting. METHODS: The present work summarizes the scientific information on nanoparticles in cancer theranostics to provide a comprehensive insight into the preventive and therapeutic potential of nanoparticles in cancer. Scopus, PubMed, Science Direct, and Google Scholar databases are searched to collect all the recent (2015-2023) scientific information on smart multifunctional nanoparticles using the terms nanotechnology, cancer theranostics, and polymer. RESULTS: The use of nanomaterials as chemical biology tools in cancer theranostics has been thoroughly investigated. They demonstrate expanded uses in terms of stability, biocompatibility, and enhanced cell permeability, enabling precision targeting and ameliorating the drawbacks of conventional cancer treatments. The nano platform presents a fascinating chance to acquire multifunctionality and targeting techniques. The production of smart nanomaterials, specifically with regard to the advent of nanotechnology, has revolutionized the diagnosis and treatment of cancer. The capability of nanoparticles to functionalize with a variety of biosubstrates, including aptamers, antibodies, DNA, and RNA, and their broad surface area allow them to encapsulate a huge number of molecules, contributing to their theranostic effect. Comparatively speaking, economical, easily produced, and less toxic nanomaterials formed from biological sources are thought to have benefits over those made using conventional processes. CONCLUSION: The present study highlights the uses of several nanoparticles (NPs), and describes numerous cancer theranostics methodologies. The benefits and difficulties preventing their adoption in cancer treatment and diagnostic applications are also critically reviewed. The use of smart nanomaterials, according to this review's findings, can considerably advance cancer theranostics and open up new avenues for tumor detection and treatment.

Role of PIM Kinase Inhibitor in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD), a neurodegenerative disorder, is the most prevalent form of senile dementia, causing progressive deterioration of cognition, behavior, and rational skills. Neuropathologically, AD is characterized by two hallmark proteinaceous aggregates: amyloid beta (Aß) plaques and neurofibrillary tangles (NFTs) formed of hyperphosphorylated tau. A significant study has been done to understand how Aß and/or tau accumulation can alter signaling pathways that affect neuronal function. A conserved protein kinase known as the mammalian target of rapamycin (mTOR) is essential for maintaining the proper balance between protein synthesis and degradation. Overwhelming evidence shows mTOR signaling's primary role in age-dependent cognitive decline and the pathogenesis of AD. Postmortem human AD brains consistently show an upregulation of mTOR signaling. Confocal microscopy findings demonstrated a direct connection between mTOR and intraneuronal Aß42 through molecular processes of PRAS40 phosphorylation. By attaching to the mTORC1 complex, PRAS40 inhibits the activity of mTOR. Furthermore, inhibiting PRAS40 phosphorylation can stop the Aß-mediated increase in mTOR activity, indicating that the accumulation of Aß may aid in PRAS40 phosphorylation. Physiologically, PRAS40 is phosphorylated by PIM1 which is a serine/threonine kinase of proto-oncogene PIM kinase family. Pharmacological inhibition of PIM1 activity prevents the Aß-induced mTOR hyperactivity in vivo by blocking PRAS40 phosphorylation and restores cognitive impairments by enhancing proteasome function. Recently identified small-molecule PIM1 inhibitors have been developed as potential therapeutic to reduce AD-neuropathology. This comprehensive study aims to address the activity of PIM1 inhibitor that has been tested for the treatment of AD, in addition to the pharmacological and structural aspects of PIM1.

Nanotechnology-Powered Meningitis Therapies: Lipid Nanoparticles Lead the Way.

The meninges serve as a protective layer, and the fluid around the brain and spinal cord can become inflamed, known as meningitis. Lipid-based pharmaceutical formulations, by their high lipophilicity, can negotiate the Blood-Brain Barrier (BBB). The current mode of treatment of meningitis is mainly through antibiotics, which, at best, is partially effective. The success of antibiotic therapy depends on several factors, for example, the difficulty of reaching the infection site, maintaining proper concentrations of the drug after crossing the BBB, and finally, its efficacy in preventing recurrent infection. In this context, interest has focused on organic and inorganic nanostructures for meningitis and transporting antibiotics to the selected region through the BBB. A focus has also been placed on several polymeric nanotechnology techniques for detecting various types of meningitis. This review focuses on nano interventions and their most recent meningitis treatments using nanotechnology.

An insight into thymidylate synthase inhibitor as anticancer agents: an explicative review.

Cancer, a widespread challenge to global health, remains a puzzle of intricate molecular dynamics. This review article delves into the mystery of cancer, with a keen focus on understanding the contributory role of thymidylate synthase (TS) in cancer. TS, a vital enzyme in DNA synthesis and repair, emerges as a significant player in the narrative of cancer development. The conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) is a major step in producing DNA. Numerous malignancies, including those of the breast, colon, lung, and ovary, have been linked to dysregulation of TS activity. Overexpression or mutations of TS lead to uncontrolled cell proliferation and tumorigenesis molecular interactions and signalling pathways involving TS come under scrutiny, revealing the nuanced connections that propel its involvement in cancer progression. Beyond overexpression and mutations, there emerges a subtle layer of regulation that involves microRNAs (miRNAs). These tiny particles attach to the TS messenger RNA, causing translational repression or its degradation, which in turn affects TS activity. Moving towards the therapeutic realm, thymidylate synthase inhibition acts as a promising anti-cancer strategy. Targeting TS with small-molecule inhibitors could provide a novel approach to treat various cancers. By reducing the number of available nucleotides, TS inhibition would slow down or halt cancer cell division, thus depriving the tumor of the building blocks required for its proliferation and growth. The aim is to assess the viability and effectiveness of targeting TS to halt or slow down cancer progression. There is growing evidence that, in comparison to traditional TS inhibitors, few novel antifolate TS inhibitors are effective against a wider variety of neoplasms, such as lung carcinomas. It has been discovered that TS inhibitors increase cancer tissues' sensitivity to chemotherapy and radiation, increasing their vulnerability to these treatments. This article aims to provide a comprehensive insight into TS, examining its cellular details, detailing the heterocyclic moieties and molecular foundations, and providing a promising future outlook.

Unlocking the Potential of RNA Nanoparticles: A Breakthrough Approach to Overcoming Challenges in Colon Cancer Treatment.

Globally, one of the leading causes of cancer-related deaths is colon cancer. As this form of cancer has a tremendous potential to metastasize, effective treatment is complicated and sometimes impossible. Despite the improvement of conventional chemotherapy and the advent of targeted therapies, overcoming multi-drug resistance (MDR) and side effects remain significant challenges. As a therapeutic intervention for targeted gene silencing in cancer, RNA technology shows promise and certain RNA-based formulations are currently undergoing clinical studies. Various studies have reported that RNA-based nanoparticles have demonstrated substantial promise for targeted medication delivery, gene therapy, and other biomedical applications. However, using RNA as a therapeutic tool presents severe limitations, mainly related to its low stability and poor cellular uptake. Nanotechnology offers a flexible and tailored alternative due to the difficulties in delivering naked RNA molecules safely in vivo, such as their short half-lives, low chemical stability, and susceptibility to nuclease degradation. In addition to shielding RNA molecules from immune system attacks and enzymatic breakdown, the nanoparticle-based delivery systems allow RNA accumulation at the tumor site. The potential of RNA and RNA-associated nanomedicines for the treatment of colon cancer, as well as the prospects for overcoming any difficulties related to mRNA, are reviewed in this study, along with the current progress of mRNA therapeutics and advancements in designing nanomaterials and delivery strategies.

Emerging therapeutic strategies in cancer therapy by HDAC inhibition as the chemotherapeutic potent and epigenetic regulator.

In developing new cancer medications, attention has been focused on novel epigenetic medicines called histone deacetylase (HDAC) inhibitors. Our understanding of cancer behavior is being advanced by research on epigenetics, which also supplies new targets for improving the effectiveness of cancer therapy. Most recently published patents emphasize HDAC selective drugs and multitarget HDAC inhibitors. Though significant progress has been made in emerging HDAC selective antagonists, it is urgently necessary to find new HDAC blockers with novel zinc-binding analogues to avoid the undesirable pharmacological characteristics of hydroxamic acid. HDAC antagonists have lately been explored as a novel approach to treating various diseases, including cancer. The complicated terrain of HDAC inhibitor development is summarized in this article, starting with a discussion of the many HDAC isotypes and their involvement in cancer biology, followed by a discussion of the mechanisms of action of HDAC inhibitors, their current level of development, effect of miRNA, and their combination with immunotherapeutic.

Molecular Insight into the Apoptotic Mechanism of Cancer Cells: An Explicative Review.

Mitosis of somatic cells produces a daughter cell. Apoptosis, a naturally programmed cellular death mechanism, kills abnormal cells produced by mitosis. Cancer can develop when this equilibrium is disrupted, either by an upsurge in cell propagation or a reduction in tissue demise. Cancer therapy aims to cause cancer cells to die while inflicting little harm to healthy cells. This review of apoptotic mechanism processes improves our understanding of how certain malignancies begin and develop. The current cancer treatments can operate either by inducing apoptosis or causing direct cell damage. An insight into the resistance to apoptosis may explicate why malignancy treatments fail in some situations. New therapies grounded on our understanding of apoptotic processes are being developed to induce apoptosis of cancer cells while limiting the simultaneous death of normal cells. Various biological activities require redox equilibrium to function properly. Antineoplastic medications that cause oxidative stress by raising ROS and blocking antioxidant mechanisms have recently attracted much interest. The rapid accumulation of ROS impairs redox balance and damages cancer cells severely. Here, we discuss ROS-instigating malignancy therapy and the antineoplastic mechanism used by prooxidative drugs.

An Insight into Synthetic Strategies, SAR Study and Anticancer Mechanism of Chalcone Derivatives: Medicinal Chemistry Perspective.

Chalcone derivatives continue to captivate medicinal chemists due to their modest chemistry, facile synthetic method, and promising biological activities. They have become wellknown in the therapeutic and pharmaceutical industries due to their diverse biological actions. These complexes offer different features and applications in a human biological system due to the flexibility of the reactions, including antimicrobial, antineoplastic, antimalarial, and other uses. As a result, chalcones have sparked much attention in malignancy research. Cancer is characterized by uncontrollably growing and spreading abnormal cells and aberrant cell behavior. These masses destroy surrounding normal tissue and can attack vital organs, leading to widespread disease. Cancer is frequently used as a warning sign for impending patient death. In the age of pharmaceutical chemistry, it is unavoidably a cause for concern and a growing weight on the populace. The pathophysiology of all malignancies is due to faulty genes that regulate the development, division, and death of cells. Various genetic and environmental variables combine to cause mutations in genes encoding essential cell-regulatory proteins, leading to the numerous alterations that characterize the evolution of cancers. Rather than directly targeting DNA synthesis, the new generation of anticancer medications target signals that promote or control the cell cycle, growth factors and their receptors, signal transduction pathways, and pathways impacting DNA repair and death. Drug hunters are focusing their attention on chalcone derivatives with varying chemical structures since they are essential in the search for anticancer drugs. Chalcone's anticancer action may be attributed to molecular changes such as drug efflux protein activities, activation of apoptosis, DNA and mitochondrial damage, inhibition of angiogenesis, tubulin inhibition, and kinase inhibition. Chalcones are used to diagnose cancer as well. The development of chalcone congeners as a prodrug or prime chemical to combat cancer necessitates a thorough investigation. This review gives an update on the different pharmacological activities of natural and synthesized chalcones in recent years. Furthermore, the structure- activity connections and processes are extensively documented, providing essential design and synthesis assistance in the future.

Unveiling Spanlastics as a Novel Carrier for Drug Delivery: A Review.

Innovative colloidal preparations that can alter the pharmacological properties of drugs have been made possible by the advancement of nanotechnology. Recent advances in the sciences of the nanoscale have led to the creation of new methods for treating illnesses. Developments in nanotechnology may lessen the side effects of medicine by using effective and regulated drug delivery methods. A promising drug delivery vehicle is spanlastics, an elastic nanovesicle that can transport a variety of drug compounds. Spanlastics have expanded the growing interest in many types of administrative pathways. Using this special type of vesicular carriers, medications intended for topical, nasal, ocular, and trans-ungual treatments are delivered to specific areas. Their elastic and malleable structure allows them to fit into skin pores, making them ideal for transdermal distribution. Spanlastic is composed of non-ionic surfactants or combinations of surfactants. Numerous studies have demonstrated how spanlastics significantly improve, drug bioavailability, therapeutic effectiveness, and reduce medication toxicity. The several vesicular systems, composition and structure of spanlastics, benefits of spanlastics over alternative drug delivery methods, and the process of drug penetration via skin are all summarized in this paper. Additionally, it provides an overview of the many medications that may be treated using spanlastic vesicles. The primary benefits of these formulations were associated with their surface properties, as a variety of proteins might be linked to the look. For instance, procedure assessment and gold nanoparticles were employed as biomarkers for different biomolecules, which included tumor label detection. Anticipate further advancements in the customization and combining of spanlastic vesicles with appropriate zeta potential to transport therapeutic compounds to specific areas for enhanced disease treatment.

A Promising Drug Candidate as Potent Therapeutic Approach for Neuroinflammation and Its In Silico Justification of Chalcone Congeners: a Comprehensive Review.

Multiple genetic, environmental, and immunological variables cause neuropsychiatric disorders (NPDs). The induced inflammatory immune response is also connected to the severity and treatment outcomes of various NPDs. These reactions also significantly impact numerous brain functions such as GABAergic signaling and neurotransmitter synthesis through inflammatory cytokines and chemokines. Chalcones (1,3-diaryl-2-propen-1-ones) and their heterocyclic counterparts are flavonoids with various biological characteristics including anti-inflammatory activity. Several pure chalcones have been clinically authorized or studied in humans. Chalcones are favored for their diagnostic and therapeutic efficacy in neuroinflammation due to their tiny molecular size, easy manufacturing, and flexibility for changes to adjust lipophilicity ideal for BBB penetrability. These compounds reached an acceptable plasma concentration and were well-tolerated in clinical testing. As a result, they are attracting increasing attention from scientists. However, chalcones' therapeutic potential remains largely untapped. This paper is aimed at highlighting the causes of neuroinflammation, more potent chalcone congeners, their mechanisms of action, and relevant structure-activity relationships.

A Comprehensive Review on Targeted Cancer Therapy: New Face of Treatment Approach.

Cancer is one of life's most difficult difficulties and a severe health risk everywhere. Except for haematological malignancies, it is characterized by unchecked cell growth and a lack of cell death, which results in an aberrant tissue mass or tumour. Vascularization promotes tumor growth, which eventually aids metastasis and migration to other parts of the body, ultimately resulting in death. The genetic material of the cells is harmed or mutated by environmental or inherited influences, which results in cancer. Presently, anti-neoplastic medications (chemotherapy, hormone, and biological therapies) are the treatment of choice for metastatic cancers, whilst surgery and radiotherapy are the mainstays for local and non-metastatic tumors. Regrettably, chemotherapy disturbs healthy cells with rapid proliferation, such as those in the gastrointestinal tract and hair follicles, leading to the typical side effects of chemotherapy. Finding new, efficient, targeted therapies based on modifications in the molecular biology of tumor cells is essential because current chemotherapeutic medications are harmful and can cause the development of multidrug resistance. These new targeted therapies, which are gaining popularity as demonstrated by the FDA-approved targeted cancer drugs in recent years, enter molecules directly into tumor cells, diminishing the adverse reactions. A form of cancer treatment known as targeted therapy goes after the proteins that regulate how cancer cells proliferate, divide, and disseminate. Most patients with specific cancers, such as chronic myelogenous leukemia (commonly known as CML), will have a target for a particular medicine, allowing them to be treated with that drug. Nonetheless, the tumor must typically be examined to determine whether it includes drug targets.

Deciphering the molecular mechanistic paths describing the chemotherapeutic potential and epigenetic regulation of curcumin in lung cancer: a mini review.

In an uncontrolled inflammatory environment, the complex process of lung carcinogenesis occurs. Lung cancer remains the leading cause of cancer-related mortality worldwide. The average 5-year survival rate is still low despite significant advancements in our knowledge of lung carcinogenesis and the development of innovative therapies in recent decades. Research on adjuvant treatment, lung carcinogenesis pathways, and possible prognostic indicators has to be refocused using an innovative approach. The majority of lung cancers are discovered at an advanced stage when there is little chance of recovery. It has grown in popularity in recent years to supplement already available chemotherapeutic therapies with adjuvant herbal medications, which may lessen toxicity and adverse effects without sacrificing therapeutic efficiency. One such prospective contender is curcumin. In-depth research has been done on curcumin as a multi-target anti-tumor and anti-inflammatory molecule. A pharmacologically active polyphenol produced from turmeric is called curcumin. Over the past few decades, curcumin's therapeutic potential has been thoroughly studied, and data indicate that curcumin may play a part in a variety of biological processes, most notably its potent anticancer activity. Being a pleiotropic chemical, curcumin regulates a variety of molecules that are key players in many cell signaling pathways. It has been shown to stifle transformation, restrain proliferation, and trigger apoptosis. Curcumin can reduce the development of non-small cell LC by downregulating Circular RNA hsa_circ_0007580, which in turn controls the expression of integrin subunit beta 1 by adsorbing miR-384. Nevertheless, despite all these advantages, curcumin's effectiveness is still restricted because of its weak bioavailability, poor absorption within the systemic circulation, and quick removal from the body. In an effort to overcome these constraints, scientists from all around the world are working to develop a synthetic and improved curcuminoid by appropriately altering the parent skeleton structurally. These curcuminoids will simultaneously improve the physicochemical properties and efficacy. This review presents evidence from the most recent clinical trials coupled with the molecular mechanisms of curcumin in LC. Curcumin as inhibitor of multiple signaling pathways expressed in lung cancer.

An Explicative Review on the Current Advancement in Schiff Base-Metal Complexes as Anticancer Agents Evolved in the Past Decade: Medicinal Chemistry Aspects.

In the recent era, developments in the field of bio-inorganic chemistry have improved interest in Schiff base complexes (imine scaffolds) for their pharmacological excellence in different areas. Schiff bases are a kind of synthetic molecule that is synthesized by the condensation reaction between a 1o amine and a carbonyl compound. Imine derivatives are also acknowledged for their ability to form complexes with several metals. Due to their wide range of biological activities, they have acquired prominence in the therapeutic and pharmaceutical industries. Inorganic chemists have continued to be intrigued by the vast range of uses of these molecules. Many of them are also thermally stable and have structural flexibility. Some of these chemicals have been discovered to be beneficial as clinical diagnostic agents as well as chemotherapeutic agents. Because of the flexibility of the reactions, these complexes have a wide range of characteristics and applications in biological systems. Anti-neoplastic activity is one of them. This review attempts to draw attention to the most notable examples of these novel compounds, which have excellent anticancer activity against different cancers. The synthetic scheme of these scaffolds, their metal complexes, and the explanation of their anticancer mechanism reported in this paper lead the researchers to design and synthesize more target-specific Schiff base congeners with little or no side effects in the future.

Molecular and Structural Insight into Adenosine A2A Receptor in Neurodegenerative Disorders: A Significant Target for Efficient Treatment Approach.

All biological tissues and bodily fluids include the autacoid adenosine. The P1 class of purinergic receptors includes adenosine receptors. Four distinct G-protein-coupled receptors on the cellular membrane mediate the effects of adenosine, whose cytoplasmic content is regulated by producing/degrading enzymes and nucleoside transporters. A2A receptor has received a great deal of attention in recent years because it has a wide range of potential therapeutic uses. A2B and, more significantly, A2A receptors regulate numerous physiological mechanisms in the central nervous system (CNS). The inferior targetability of A2B receptors towards adenosine points that they might portray a promising medicinal target since they are triggered only under pharmacological circumstances (when adenosine levels rise up to micromolar concentrations). The accessibility of specific ligands for A2B receptors would permit the exploration of such a theory. A2A receptors mediate both potentially neurotoxic and neuroprotective actions. Hence, it is debatable to what extent they play a role in neurodegenerative illnesses. However, A2A receptor blockers have demonstrated clear antiparkinsonian consequences, and a significant attraction exists in the role of A2A receptors in other neurodegenerative disorders. Amyloid peptide extracellular accumulation and tau hyperphosphorylation are the pathogenic components of AD that lead to neuronal cell death, cognitive impairment, and memory loss. Interestingly, in vitro and in vivo research has shown that A2A adenosine receptor antagonists may block each of these clinical symptoms, offering a crucial new approach to combat a condition for which, regrettably, only symptomatic medications are currently available. At least two requirements must be met to determine whether such receptors are a target for diseases of the CNS: a complete understanding of the mechanisms governing A2A-dependent processes and the availability of ligands that can distinguish between the various receptor populations. This review concisely summarises the biological effects mediated by A2A adenosine receptors in neurodegenerative disorders and discusses the chemical characteristics of A2A adenosine receptor antagonists undergoing clinical trials. Selective A2A receptor blocker against neurodegenerative disorders.

Molecular Insights on Selective and Specific Inhibitors of Cyclin Dependent Kinase 9 Enzyme (CDK9) for the Purpose of Cancer Therapy.

Cyclin Dependent Kinase 9 (CDK9), which controls transcriptional elongation, is a promising pharmacological target for a variety of cancerous cells, specifically those characterized by transcriptional dysregulation. CDK9 promotes the pause or release of RNA polymerase II, a rate-limiting stage in normal transcriptional regulation that is often disturbed in cancers. New indications suggest that selective CDK9 antagonism may be beneficial in the treatment of some cancers. CDK9 modulators (inhibitors and degraders) have gained a lot of attention recently, and many molecules are currently in clinical trials. In this review, the CDK9 antagonists under clinical and preclinical trials have been discussed, as well as the structure-activity relationship has been studied, which will help scientists generate more target- specific drug molecules in the future with less toxicity.

Plant Bioactives in the Treatment of Inflammation of Skeletal Muscles: A Molecular Perspective.

Skeletal muscle mass responds rapidly to growth stimuli, precipitating hypertrophies (increased protein synthesis) and hyperplasia (activation of the myogenic program). For ages, muscle degeneration has been attributed to changes in the intracellular myofiber pathways. These pathways are tightly regulated by hormones and lymphokines that ultimately pave the way to decreased anabolism and accelerated protein breakdown. Despite the lacunae in our understanding of specific pathways, growing bodies of evidence suggest that the changes in the myogenic/regenerative program are the major contributing factor in the development and progression of muscle wasting. In addition, inflammation plays a key role in the pathophysiology of diseases linked to the failure of skeletal muscles. Chronic inflammation with elevated levels of inflammatory mediators has been observed in a spectrum of diseases, such as inflammatory myopathies and chronic obstructive pulmonary disease (COPD). Although the pathophysiology of these diseases varies greatly, they all demonstrate sarcopenia and dysregulated skeletal muscle physiology as common symptoms. Medicinal plants harbor potential novel chemical moieties for a plenitude of illnesses, and inflammation is no exception. However, despite the vast number of potential antiinflammatory compounds found in plant extracts and isolated components, the research on medicinal plants is highly daunting. This review aims to explore the various phytoconstituents employed in the treatment of inflammatory responses in skeletal muscles, while providing an in-depth molecular insight into the latter.

Pyrazole Scaffolds: Centrality in Anti-Inflammatory and Antiviral Drug Design.

BACKGROUND: Pyrazole is a component of a diversity of bioactive heterocyclic congeners with a broad-spectrum range of biological and pharmacological uses. Designing novel pyrazole and its analogues, revealing new routes for synthesizing this nucleus, exploring various potencies of that heterocycles, and looking for possible applications of pyrazoles are all becoming more important due to their numerous potential applications. OBJECTIVES: Pyrazole scaffolds have been proven to be successful as anti-viral and anti-inflammatory therapeutics against multiple targets like HSV-1, NNRTI, H1N1, CoX-1, and CoX-2. Due to this miscellany in the biotic area, this moiety has engrossed the consideration of many scientists to study chemistry and pharmacological profile. RESULTS: The review encompasses pyrazole having various scaffolds with multiple biological activities and attempts have also been made to correlate their structure-activity relationship. Multiple pyrazole correspondents have been synthesized as lead molecules and performed valuation for their actions. CONCLUSION: The incorporation of pyrazole with other pharmacophores in the molecule might lead to novel potent therapeutic agents that will further help in designing potent lead molecules.

A Molecular Insight into Pyrazole Congeners as Antimicrobial, Anticancer, and Antimalarial Agents.

BACKGROUND: Pyrazole is a bioactive heterocyclic congener with numerous biological and pharmacological functionalities. Due to their multiple prospective applications, developing innovative and novel pyrazoles and analogs, revealing revolutionary methods for synthesizing this nucleus, investigating diverse potencies of that heterocycle, and exploring possible pyrazole applications are becoming increasingly relevant. OBJECTIVES: Pyrazole scaffolds have been proven successful as antimicrobial, anticancer, and antimalarial therapeutics against multiple targets like DNA gyrase, topoisomerase IV, Hsp90, and several kinase enzymes. For this variability in the biotic zone, their moiety has gained the attention of many scientists interested in researching chemical and pharmacological profiles. RESULTS: The review covers pyrazole scaffolds with a variety of biological functions and attempts to connect the structure-activity relationship. Multiple pyrazole analogs have been produced as lead compounds, and their activities have been evaluated. CONCLUSION: The combination of pyrazole with other pharmacophores in a molecule might lead to novel potent therapeutic medicines, which could aid in the development of potent lead compounds.