Green Synthesis of Silver Nanoparticles and their Potential Applications in Mitigating Cancer.

In recent years, the field of nanotechnology has brought about significant advancements that have transformed the landscape of disease diagnosis, prevention, and treatment, particularly in the realm of medical science. Among the various approaches to nanoparticle synthesis, the green synthesis method has garnered increasing attention. Silver nanoparticles (AgNPs) have emerged as particularly noteworthy nanomaterials within the spectrum of metallic nanoparticles employed for biomedical applications. AgNPs possess several key attributes that make them highly valuable in the biomedical field. They are biocompatible, cost-effective, and environmentally friendly, rendering them suitable for various bioengineering and biomedical applications. Notably, AgNPs have found a prominent role in the domain of cancer diagnosis. Research investigations have provided evidence of AgNPs' anticancer activity, which involves mechanisms such as DNA damage, cell cycle arrest, induction of apoptosis, and the regulation of specific cytokine genes. The synthesis of AgNPs primarily involves the reduction of silver ions by reducing agents. Interestingly, natural products and living organisms have proven to be effective sources for the generation of precursor materials used in AgNP synthesis. This comprehensive review aims to summarize the key aspects of AgNPs, including their characterization, properties, and recent advancements in the field of biogenic AgNP synthesis. Furthermore, the review highlights the potential applications of these nanoparticles in combating cancer.

Synthetic and Natural Bioactive Molecules in Balancing the Crosstalk among Common Signaling Pathways in Alzheimer's Disease: Understanding the Neurotoxic Mechanisms for Therapeutic Intervention.

The structure and function of the brain greatly rely on different signaling pathways. The wide variety of biological processes, including neurogenesis, axonal remodeling, the development and maintenance of pre- and postsynaptic terminals, and excitatory synaptic transmission, depends on combined actions of these molecular pathways. From that point of view, it is important to investigate signaling pathways and their crosstalk in order to better understand the formation of toxic proteins during neurodegeneration. With recent discoveries, it is established that the modulation of several pathological events in Alzheimer's disease (AD) due to the mammalian target of rapamycin (mTOR), Wnt signaling, 5'-adenosine monophosphate activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), and sirtuin 1 (Sirt1, silent mating-type information regulator 2 homologue 1) are central to the key findings. These include decreased amyloid formation and inflammation, mitochondrial dynamics control, and enhanced neural stability. This review intends to emphasize the importance of these signaling pathways, which collectively determine the fate of neurons in AD in several ways. This review will also focus on the role of novel synthetic and natural bioactive molecules in balancing the intricate crosstalk among different pathways in order to prolong the longevity of AD patients.

Repurposing approved non-oncology drugs for cancer therapy: a comprehensive review of mechanisms, efficacy, and clinical prospects.

Cancer poses a significant global health challenge, with predictions of increasing prevalence in the coming years due to limited prevention, late diagnosis, and inadequate success with current therapies. In addition, the high cost of new anti-cancer drugs creates barriers in meeting the medical needs of cancer patients, especially in developing countries. The lengthy and costly process of developing novel drugs further hinders drug discovery and clinical implementation. Therefore, there has been a growing interest in repurposing approved drugs for other diseases to address the urgent need for effective cancer treatments. The aim of this comprehensive review is to provide an overview of the potential of approved non-oncology drugs as therapeutic options for cancer treatment. These drugs come from various chemotherapeutic classes, including antimalarials, antibiotics, antivirals, anti-inflammatory drugs, and antifungals, and have demonstrated significant antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties. A systematic review of the literature was conducted to identify relevant studies on the repurposing of approved non-oncology drugs for cancer therapy. Various electronic databases, such as PubMed, Scopus, and Google Scholar, were searched using appropriate keywords. Studies focusing on the therapeutic potential, mechanisms of action, efficacy, and clinical prospects of repurposed drugs in cancer treatment were included in the analysis. The review highlights the promising outcomes of repurposing approved non-oncology drugs for cancer therapy. Drugs belonging to different therapeutic classes have demonstrated notable antitumor effects, including inhibiting cell proliferation, promoting apoptosis, modulating the immune response, and suppressing metastasis. These findings suggest the potential of these repurposed drugs as effective therapeutic approaches in cancer treatment. Repurposing approved non-oncology drugs provides a promising strategy for addressing the urgent need for effective and accessible cancer treatments. The diverse classes of repurposed drugs, with their demonstrated antiproliferative, pro-apoptotic, immunomodulatory, and antimetastatic properties, offer new avenues for cancer therapy. Further research and clinical trials are warranted to explore the full potential of these repurposed drugs and optimize their use in treating various cancer types. Repurposing approved drugs can significantly expedite the process of identifying effective treatments and improve patient outcomes in a cost-effective manner.

Evolution of Natural Product Scaffolds as Potential Proteasome Inhibitors in Developing Cancer Therapeutics.

Homeostasis between protein synthesis and degradation is a critical biological function involving a lot of precise and intricate regulatory systems. The ubiquitin-proteasome pathway (UPP) is a large, multi-protease complex that degrades most intracellular proteins and accounts for about 80% of cellular protein degradation. The proteasome, a massive multi-catalytic proteinase complex that plays a substantial role in protein processing, has been shown to have a wide range of catalytic activity and is at the center of this eukaryotic protein breakdown mechanism. As cancer cells overexpress proteins that induce cell proliferation, while blocking cell death pathways, UPP inhibition has been used as an anticancer therapy to change the balance between protein production and degradation towards cell death. Natural products have a long history of being used to prevent and treat various illnesses. Modern research has shown that the pharmacological actions of several natural products are involved in the engagement of UPP. Over the past few years, numerous natural compounds have been found that target the UPP pathway. These molecules could lead to the clinical development of novel and potent anticancer medications to combat the onslaught of adverse effects and resistance mechanisms caused by already approved proteasome inhibitors. In this review, we report the importance of UPP in anticancer therapy and the regulatory effects of diverse natural metabolites, their semi-synthetic analogs, and SAR studies on proteasome components, which may aid in discovering a new proteasome regulator for drug development and clinical applications.

Clinical Biomarkers and Novel Drug Targets to Cut Gordian Knots of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD), the primary cause of dementia, escalating worldwide, has no proper diagnosis or effective treatment. Neuronal cell death and impairment of cognitive abilities, possibly triggered by several brain mechanisms, are the most significant characteristic of this disorder. METHODS: A multitude of pharmacological targets have been identified for potential drug design against AD. Although many advances in treatment strategies have been made to correct various abnormalities, these often exhibit limited clinical significance because this disease aggressively progresses into different regions of the brain, causing severe deterioration. RESULTS: These biomarkers can be game-changers for early detection and timely monitoring of such disorders. CONCLUSION: This review covers clinically significant biomarkers of AD for precise and early monitoring of risk factors and stages of this disease, the potential site of action and novel targets for drugs, and pharmacological approaches to clinical management.

Dysfunction of ABC Transporters at the Surface of BBB: Potential Implications in Intractable Epilepsy and Applications of Nanotechnology Enabled Drug Delivery.

Epilepsy is a chronic neurological disorder affecting 70 million people globally. One of the fascinating attributes of brain microvasculature is the (BBB), which controls a chain of distinct features that securely regulate the molecules, ions, and cells movement between the blood and the parenchyma. The barrier's integrity is of paramount importance and essential for maintaining brain homeostasis, as it offers both physical and chemical barriers to counter pathogens and xenobiotics. Dysfunction of various transporters in the (BBB), mainly ATP binding cassette (ABC), is considered to play a vital role in hampering the availability of antiepileptic drugs into the brain. ABC (ATP-binding cassette) transporters constitute a most diverse protein superfamily, which plays an essential part in various biological processes, including cell homeostasis, cell signaling, uptake of nutrients, and drug metabolism. Moreover, it plays a crucial role in neuroprotection by out-flowing various internal and external toxic substances from the interior of a cell, thus decreasing their buildup inside the cell. In humans, forty-eight ABC transporters have been acknowledged and categorized into subfamilies A to G based on their phylogenetic analysis. ABC subfamilies B, C, and G, impart a vital role at the BBB in guarding the brain against the entrance of various xenobiotic and their buildup. The illnesses of the central nervous system have received a lot of attention lately Owing to the existence of the BBB, the penetration effectiveness of most CNS medicines into the brain parenchyma is very limited (BBB). In the development of neurological therapies, BBB crossing for medication delivery to the CNS continues to be a major barrier. Nanomaterials with BBB cross ability have indeed been extensively developed for the treatment of CNS diseases due to their advantageous properties. This review will focus on multiple possible factors like inflammation, oxidative stress, uncontrolled recurrent seizures, and genetic polymorphisms that result in the deregulation of ABC transporters in epilepsy and nanotechnology-enabled delivery across BBB in epilepsy.

A Comprehensive Review on Journey of Pyrrole Scaffold Against Multiple Therapeutic Targets.

Heterocyclic compounds are that type of substances that are deeply intertwined with biological processes. Heterocycles are found in about 90% of commercially available medicines. In medicinal chemistry, finding new synthetic molecules with drug-like characteristics is a regular problem, which triggered the development of pharmacological molecules, the majority of which are based on N-heterocyclic motifs. Among the heterocycles, the pyrrole scaffold is the most commonly found heterocycle in both natural and synthetic bioactive compounds. Pyrrole has a fivemembered heterocyclic ring with a plethora of pharmacophores, resulting in a library of different lead compounds. Pyrrole derivatives are physiologically active heterocyclic compounds that can be used as scaffolds for antibacterial, antiviral, anticancer, antitubercular, anti-inflammatory, and as enzyme inhibitors. On account of their extensive pharmacological profile, pyrrole and its various synthetic derivatives have drawn much attention from researchers to explore it for the benefit of humankind. This review presents an overview of recent developments in the pyrrole derivatives against multiple therapeutic targets.

Anticancer Potential of Thymoquinone: A Novel Bioactive Natural Compound from Nigella sativa L.

Cancer involves the uncontrolled division of cells resulting in abnormal cell growth due to various gene mutations and is considered the second major cause of death. Due to drug resistance to current anticancer drugs, cancer incidence is rising, and seeking effective treatment is a major concern. Natural products are prospective to yield unique molecules, as nature is a leading source of various drug molecules due to plenty of pharmacologically active molecules. Thymoquinone, a bioactive constituent obtained from Nigella sativa L., has drawn considerable attention among researchers in recent years due to its anticancer potential involving various molecular targets, including initiation of apoptosis initiation, arrest of cell cycle and generation of ROS, besides targeting multiple kinases such as tyrosine kinase, MAPK, and Janus kinase. The current review summarizes the thymoquinone chemistry, sources and anticancer potential involving various molecular targets.

Bioactive Heterocyclic Compounds as Potential Therapeutics in the Treatment of Gliomas: A Review.

Cancer is one of the most alarming diseases, with an estimation of 9.6 million deaths in 2018. Glioma occurs in glial cells surrounding nerve cells. The majority of the patients with gliomas have a terminal prognosis, and the ailment has significant sway on patients and their families, be it physical, psychological, or economic wellbeing. As Glioma exhibits, both intra and inter tumour heterogeneity with multidrug resistance and current therapies are ineffective. So the development of safer anti gliomas agents is the need of hour. Bioactive heterocyclic compounds, eithernatural or synthetic, are of potential interest since they have been active against different targets with a wide range of biological activities, including anticancer activities. In addition, they can cross the biological barriers and thus interfere with various signalling pathways to induce cancer cell death. All these advantages make bioactive natural compounds prospective candidates in the management of glioma. In this review, we assessed various bioactive heterocyclic compounds, such as jaceosidin, hispudlin, luteolin, silibinin, cannabidiol, tetrahydrocannabinol, didemnin B, thymoquinone, paclitaxel, doxorubicin, and cucurbitacins for their potential anti-glioma activity. Also, different kinds of chemical reactions to obtain various heterocyclic derivatives, e.g. indole, indazole, benzimidazole, benzoquinone, quinoline, quinazoline, pyrimidine, and triazine, are listed.

Ethnomedicinal uses, Phytochemistry and Pharmacological Aspects of the Genus Berberis Linn: A Comprehensive Review.

BACKGROUND: Genus Berberis (family Berberidaceae), which contains about 650 species and 17 genera worldwide, has been used in folklore and various traditional medicine systems. Berberis Linn. is the most established group among genera with around 450-500 species across the world. This comprehensive review will not only help researchers for further evaluation but also provide substantial information for future exploitation of species to develop novel herbal formulations. OBJECTIVE: The present review is focussed to summarize and collect the updated review of information of Berberis species reported to date regarding their ethnomedicinal information, chemical constituents, traditional/folklore use, and reported pharmacological activities on more than 40 species of Berberis. CONCLUSION: A comprehensive survey of the literature reveals that various species of the genus possess various phytoconstituents mainly alkaloids, flavonoid based compounds isolated from different parts of a plant with a wide range of pharmacological activities. So far, many pharmacological activities like anti-cancer, anti-hyperlipidemic, hepatoprotective, immunomodulatory, antiinflammatory both in vitro and in vivo and clinical study of different extracts/isolated compounds of different species of Berberis have been reported, proving their importance as a medicinal plant and claiming their traditional use.