Current Drug Targets - Volume 23, Issue 9, 2022

Organic or inorganic compounds are synthesized or formulated to demonstrate their therapeutic actions, like a natural polysaccharide in the body. Polysaccharides, the major type of natural polymers, are biologically active, non-toxic, hydrophilic, and biodegradable and exhibit various properties. This manuscript is focused on delivering anticancer drugs with the help of mimetic components of polysaccharides. The data presented in this manuscript were obtained from PubMed, Elsevier, Taylor & Francis and Bentham Science Journals. Most chemotherapeutics are toxic to the human body, have a narrow therapeutic index, sluggish pharmaceutical delivery mechanisms, and are poorly soluble in water. The use of mimetic components of polysaccharides leads to the enhancement of the solubility of drugs in the biological environment. The current review summarizes the use of mimetic components of polysaccharides along with anticancer agents, which are capable of inhibiting the growth of cancerous cells in the body and exhibiting lesser adverse effects in the biological system compared to other therapies.

The commensal microbiota is known to regulate host physiology. Dysbiosis or compromised resilience in the microbial ecology is related to the impending risk of cancer. A potential link between cancer and microbiota is indicated by a lot of evidence. The current review explores in detail the various links leading to and /or facilitating oncogenesis, providing sound reasoning or a basis for its utilization as potential therapeutic targets. The present review emphasizes the existing knowledge of the microbiome in cancer and further elaborates on the factors, like genetic modifications, effects of dietary components, and environmental agents, that are considered to assess the direct and indirect effect of microbes in the process of oncogenesis and on the host’s health. Strategies modulating the microbiome and novel biotherapeutics are also discussed. Pharmacomicrobiomics is one such niche accounting for the interplay between the microbiome, xenobiotic, and host responses, which is also looked upon. The literature search strategy for this review was conducted by following the methodology of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The method includes the collection of data from different search engines, like PubMed, ScienceDirect, SciFinder, etc., to get coverage of relevant literature for accumulating appropriate information regarding microbiome, cancer, and their linkages. These considerations are made to expand the existing literature on the role of gut microbiota in the host's health, the interaction between host and microbiota, and the reciprocal relationship between the microbiome and modified neoplastic cells. Potential therapeutic implications of cancer microbiomes that are yet unexplored and have rich therapeutic dividends improving human health are discussed in detail in this review.

Parkinson's disease is a chronic and gradually progressive neurodegenerative disorder triggered due to the loss of dopamine-releasing neurons in the region of substantia nigra pars compacta characterized by the motor symptoms, such as tremor, bradykinesia, akinesia, and postural instability. Proteinopathies, mitochondrial dysfunction induced dopaminergic neuronal deterioration, and gene mutations are the hallmarks of Parkinson's disease. The bioactive components of Brahmi, such as Bacoside A, Bacoside B, and Bacosaponins, belong to various chemical families. Brahmi's neuroprotective role includes reducing neuronal oxidative stress, dopaminergic neuronal degeneration, mitochondrial dysfunction, inflammation, inhibition of α-synuclein aggregation, and improvement of cognitive and learning behaviour. Researchers found that Bacopa monnieri significantly increased brain levels of glutathione, vitamin C, vitamin E, and vitamin A in rats exposed to cigarette smoke. Brahmi has a potent antioxidant property and neuroprotective effects against PD that help reduce oxidative stress and neuroinflammation and enhance dopamine levels. The review collates all the preclinical studies that prove the beneficial neuroprotective effect of Brahmi for treating PD.

The vascular endothelium is the innermost lining of blood vessels, which maintains vasoconstriction and vasodilation. Loss of vascular tone is a hallmark for cardiovascular disorders. Numerous factors, such as over-activation of the renin-angiotensin-aldosterone system, kinases, growth factors, etc., play a crucial role in the induction and progression of vascular abrasion. Interestingly, dysregulation of these pathways either enhances the intensity of oxidative stress, or these pathways are affected by oxidative stress. Thus, oxidative stress has been considered a key culprit in the progression of vascular endothelial dysfunction. Oxidative stress induced by reactive oxygen and nitrogen species causes abnormal gene expression, alteration in signal transduction, and the activation of pathways, leading to induction and progression of vascular injury. In addition, numerous antioxidants have been noted to possess promising therapeutic potential in preventing the development of vascular endothelial dysfunction. Therefore, we have focused on current perspectives in oxidative stress signalling to evaluate common biological processes whereby oxidative stress plays a crucial role in the progression of vascular endothelial dysfunction.

Chemobrain is one of the major side effects of chemotherapy; despite increased research, the mechanisms underlying chemotherapy-induced cognitive changes remain unknown. Several possibly important candidate mechanisms have been identified and will be studied further in the future. Chemobrain is characterized by memory loss, cognitive impairment, difficulty in language, concentration, acceleration, and learning. The major characteristic of chemobrain is oxidative stress, mitochondrial dysfunction, immune dysregulation, hormonal alteration, white matter abnormalities, and DNA damage. Berberine (BBR) is an isoquinoline alkaloid extracted from various berberine species. BBR is a small chemical that easily passes the blood-brain barrier (BBB), making it useful for treating neurodegenerative diseases. Many studies on the pharmacology of BBR have been reported in the past. Furthermore, several clinical and experimental research indicates that BBR has a variety of pharmacological effects. So, in this review, we explore the pathogenesis of chemobrain and the neuroprotective potential of BBR against chemobrain. We also introduced the therapeutic role of BBR in various neurodegenerative and neurological diseases such as Alzheimer's, Parkinson's disease, mental depression, schizophrenia, anxiety, and also some stroke.

Pegfilgrastim-apgf (nyvepria) was currently approved by FDA for the treatment of febrile neutropenia associated with non-myeloid malignancies receiving myelosuppressive anticancer drugs. It was developed by Pfizer, USA. It is a PEGylated leukocyte growth-stimulating factor indicated to reduce the incidence of febrile neutropenia in patients receiving anticancer drugs. Nyvepria is biosimilar to pegfilgrastim, approved by FDA on June 10, 2020. It is the fourth FDA-approved drug for the treatment of infection exhibiting febrile neutropenia. This review abridges the indicators in the development of nyvepria foremost to approval for the treatment of febrile neutropenia (FN), a biosimilar regulatory framework, and current updates on the clinical trials (CTs).

Alzheimer’s disease (AD) is an irreversible, progressive neurodegenerative disorder that may account for approximately 60-70% of cases of dementia worldwide. AD is characterized by impaired behavioural and cognitive functions, including memory, language, conception, attentiveness, judgment, and reasoning problems. The two important hallmarks of AD are the appearance of plaques and tangles of amyloid-beta (Aβ) and tau proteins, respectively, in the brain based on the etiology of the disease, including cholinergic impairment, metal dyshomeostasis, oxidative stress, and degradation of neurotransmitters. Currently, the used medication only provides alleviation of symptoms but is not effective in curing the disease, which creates the need to develop new molecules to treat AD. Heterocyclic compounds have proven their ability to be developed as drugs for the treatment of various diseases. The five-membered heterocyclic compound triazole has received foremost fascination for the discovery of new drugs due to the possibility of structural variation. Moreover, it has proved its significance in various drug categories. This review mainly summarizes the recent advancements in the development of novel 1,2,3-triazole and 1,2,4-triazole-based molecules in the drug discovery process for targeting various AD targets such as phosphodiesterase 1 (PDE1) inhibitors, apoptosis signal-regulating kinase 1 (ASK1) inhibitors, somatostatin receptor subtype-4 (SSTR4) agonist, several other druggable targets, molecular modelling studies, as well as various methodologies for the synthesis of triazoles containing molecules such as click reaction, Pellizzari reaction, and Einhorn- Brunner reaction.