Design and development of new inhibitors against breast cancer, Monkeypox and Marburg virus by modification of natural Fisetin via in silico and SAR studies.

The natural Fisetin and its derivatives have been shown to have effective bioactivity and strong pharmacological profile, which is continuously drawing the interest of therapeutic applications to the development of new biomolecules against Breast cancer and Monkeypox, and Marburg viral infection, while computational approaches and the study of their structure-activity relationship (SAR) are the most eloquent and reliable platform for performing their hypothetical profile renovation. So, the main perspective of this investigation is to evaluate dual function of Fisetin and its derivatives against both virus and cancerous target. First and foremost, the prediction of activity spectra for materials (PASS) valuation has provided preliminary data on the antiviral, antibacterial, antiparasitic, and anti-cancer possibilities of the mentioned compounds. According to the evidence, PASS predicted scores were shown to perform better in antineoplastic and antiviral than antibacterial, and antiparasitic efficiency; as evidenced by their higher PASS scores in antineoplastic and antiviral drug tests. Breast cancer, Monkeypox, and Marburg virus have been selected as targeted pathogens, and different in silico studies were conducted to determine the dual function of mention derivatives. The "Lipinski five rules," on the other hand, has been subjected to extensive testing for drug-like characteristics. Molecular docking against Breast cancer, Monkeypox, and Marburg virus have been accomplished after confirmation of their bioactivity. The molecular docking evaluation against targeted disease displayed re-markable binding affinity and non-bonding engagement, with most of the results indicating that derivatives are more effective than the FDA approved standard antiviral, and antineoplastic drugs. Finally, the ADMET characteristics have been computed, and they indicate that the substance is suitable to use and did not have any chance to produce adverse effects on aquatic or non-aquatic environment, as well as having a highly soluble capacity in water medium, high G.I absorption rate, with outstanding bioavailability index. Therefore, these mentioned Fisetin derivatives could be suggested as potential medication against Breast cancer and newly reported Monkeypox, and Marburg virus, and may further proceed for laboratory experiment, synthesis, and clinical trials to evaluate their practical value.

Food Color Additives in Hazardous Consequences of Human Health: An Overview.

Food color additives are used to make food more appetizing. The United States Food and Drug Administration (FDA) permitted nine artificial colorings in foods, drugs, and cosmetics, whereas the European Union (EU) approved five artificial colors (E-104, 122, 124, 131, and 142) for food. However, these synthetic coloring materials raise various health hazards. The present review aimed to summarize the toxic effects of these coloring food additives on the brain, liver, kidney, lungs, urinary bladder, and thyroid gland. In this respect, we aimed to highlight the scientific evidence and the crucial need to assess potential health hazards of all colors used in food on human and nonhuman biota for better scrutiny. Blue 1 causes kidney tumor in mice, and there is evidence of death due to ingestion through a feeding tube. Blue 2 and Citrus Red 2 cause brain and urinary bladder tumors, respectively, whereas other coloring additives may cause different types of cancers and numerous adverse health effects. In light of this, this review focuses on the different possible adverse health effects caused by these food coloring additives, and possible ways to mitigate or avoid the damage they may cause. We hope that the data collected from in vitro or in vivo studies and from clinical investigations related to the possible health hazards of food color additives will be helpful to both researchers and the food industry in the future.

Exposure of metal toxicity in Alzheimer's disease: An extensive review.

Metals serve important roles in the human body, including the maintenance of cell structure and the regulation of gene expression, the antioxidant response, and neurotransmission. High metal uptake in the nervous system is harmful because it can cause oxidative stress, disrupt mitochondrial function, and impair the activity of various enzymes. Metal accumulation can cause lifelong deterioration, including severe neurological problems. There is a strong association between accidental metal exposure and various neurodegenerative disorders, including Alzheimer's disease (AD), the most common form of dementia that causes degeneration in the aged. Chronic exposure to various metals is a well-known environmental risk factor that has become more widespread due to the rapid pace at which human activities are releasing large amounts of metals into the environment. Consequently, humans are exposed to both biometals and heavy metals, affecting metal homeostasis at molecular and biological levels. This review highlights how these metals affect brain physiology and immunity and their roles in creating harmful proteins such as ß-amyloid and tau in AD. In addition, we address findings that confirm the disruption of immune-related pathways as a significant toxicity mechanism through which metals may contribute to AD.

In silico investigation and potential therapeutic approaches of natural products for COVID-19: Computer-aided drug design perspective.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a substantial number of deaths around the world, making it a serious and pressing public health hazard. Phytochemicals could thus provide a rich source of potent and safer anti-SARS-CoV-2 drugs. The absence of approved treatments or vaccinations continues to be an issue, forcing the creation of new medicines. Computer-aided drug design has helped to speed up the drug research and development process by decreasing costs and time. Natural compounds like terpenoids, alkaloids, polyphenols, and flavonoid derivatives have a perfect impact against viral replication and facilitate future studies in novel drug discovery. This would be more effective if collaboration took place between governments, researchers, clinicians, and traditional medicine practitioners' safe and effective therapeutic research. Through a computational approach, this study aims to contribute to the development of effective treatment methods by examining the mechanisms relating to the binding and subsequent inhibition of SARS-CoV-2 ribonucleic acid (RNA)-dependent RNA polymerase (RdRp). The in silico method has also been employed to determine the most effective drug among the mentioned compound and their aquatic, nonaquatic, and pharmacokinetics' data have been analyzed. The highest binding energy has been reported -11.4 kcal/mol against SARS-CoV-2 main protease (7MBG) in L05. Besides, all the ligands are non-carcinogenic, excluding L04, and have good water solubility and no AMES toxicity. The discovery of preclinical drug candidate molecules and the structural elucidation of pharmacological therapeutic targets have expedited both structure-based and ligand-based drug design. This review article will assist physicians and researchers in realizing the enormous potential of computer-aided drug design in the design and discovery of therapeutic molecules, and hence in the treatment of deadly diseases.

Polyphenols Targeting Oxidative Stress in Spinal Cord Injury: Current Status and Future Vision.

A spinal cord injury (SCI) occurs when the spinal cord is deteriorated or traumatized, leading to motor and sensory functions lost even totally or partially. An imbalance within the generation of reactive oxygen species and antioxidant defense levels results in oxidative stress (OS) and neuroinflammation. After SCI, OS and occurring pathways of inflammations are significant strenuous drivers of cross-linked dysregulated pathways. It emphasizes the significance of multitarget therapy in combating SCI consequences. Polyphenols, which are secondary metabolites originating from plants, have the promise to be used as alternative therapeutic agents to treat SCI. Secondary metabolites have activity on neuroinflammatory, neuronal OS, and extrinsic axonal dysregulated pathways during the early stages of SCI. Experimental and clinical investigations have noted the possible importance of phenolic compounds as important phytochemicals in moderating upstream dysregulated OS/inflammatory signaling mediators and axonal regeneration's extrinsic pathways after the SCI probable significance of phenolic compounds as important phytochemicals in mediating upstream dysregulated OS/inflammatory signaling mediators. Furthermore, combining polyphenols could be a way to lessen the effects of SCI.

Multifaceted role of natural sources for COVID-19 pandemic as marine drugs.

COVID-19, which is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly spread over the world, posing a global health concern. The ongoing epidemic has necessitated the development of novel drugs and potential therapies for patients infected with SARS-CoV-2. Advances in vaccination and medication development, no preventative vaccinations, or viable therapeutics against SARS-CoV-2 infection have been developed to date. As a result, additional research is needed in order to find a long-term solution to this devastating condition. Clinical studies are being conducted to determine the efficacy of bioactive compounds retrieved or synthesized from marine species starting material. The present study focuses on the anti-SARS-CoV-2 potential of marine-derived phytochemicals, which has been investigated utilizing in in silico, in vitro, and in vivo models to determine their effectiveness. Marine-derived biologically active substances, such as flavonoids, tannins, alkaloids, terpenoids, peptides, lectins, polysaccharides, and lipids, can affect SARS-CoV-2 during the viral particle's penetration and entry into the cell, replication of the viral nucleic acid, and virion release from the cell; they can also act on the host's cellular targets. COVID-19 has been proven to be resistant to several contaminants produced from marine resources. This paper gives an overview and summary of the various marine resources as marine drugs and their potential for treating SARS-CoV-2. We discussed at numerous natural compounds as marine drugs generated from natural sources for treating COVID-19 and controlling the current pandemic scenario.

Bioactive Compounds and Diabetes Mellitus: Prospects and Future Challenges.

Diabetes mellitus is a metabolic condition that influences the endocrine framework. Hyperglycemia and hyperlipidemia are two of the most widely recognized metabolic irregularities in diabetes and two of the most well-known reasons for diabetic intricacies. Diabetes mellitus is a persistent illness brought about by metabolic irregularities in hyperglycemic pancreatic cells. Hyperglycemia can be brought about by an absence of insulin-producing beta cells in the pancreas (Type 1 diabetes mellitus) or inadequate insulin creation that does not work effectively (Type 2 diabetes mellitus). Present diabetes medication directs blood glucose levels in the systemic circulation to the typical levels. Numerous advanced prescription medicines have many negative results that can bring about unexpected severe issues during treatment of the bioactive compound from a different source that is beneficially affected by controlling and adjusting metabolic pathways or cycles. Moreover, a few new bioactive medications disengaged from plants have shown antidiabetic action with more noteworthy adequacy than the oral hypoglycemic agent that specialists have utilized in clinical treatment lately. Since bioactive mixtures are collected from familiar sources, they have a great activity in controlling diabetes mellitus. This study discusses bioactive compounds, their activity in managing diabetes mellitus, and their prospects. Though bioactive compounds have many health-beneficial properties, adequate clinical studies still need to acknowledge that they effectively manage diabetes mellitus.

Nanotechnology-based Approaches and Investigational Therapeutics against COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus responsible for the current global pandemic, which first emerged in December 2019. This coronavirus has affected 217 countries worldwide, most of which have enacted non-remedial preventive measures, such as nationwide lockdowns, work from home, travel bans, and social isolation. Pharmacists, doctors, nurses, technologists, and other healthcare professionals have played pivotal roles during this pandemic. Unfortunately, confirmed drugs have not been identified for the treatment of patients with coronavirus disease 2019 (COVID-19) caused by SARSCoV2; however, favipiravir and remdesivir have been reported as promising antiviral drugs. Some vaccines have already been developed, and vaccination is ongoing globally. Various nanotechnologies are currently being developed in many countries for preventing SARS-CoV-2 spread and treating COVID-19 infections. In this article, we present an overview of the COVID-19 pandemic situation and discuss nanotechnology-based approaches and investigational therapeutics for COVID-19.

In vitro comparative quality evaluation of different brands of esomeprazole tablets available in selected community pharmacies in Dhaka, Bangladesh.

OBJECTIVE: Esomeprazole is the S-isomer of omeprazole, used to treat gastro esophageal reflux disease. It is one of the widely manufactured and marketed drugs by many pharmaceutical companies in Bangladesh. The aim of the study is to compare the different physical parameters including hardness, friability, diameter, thickness, disintegration time, dissolution test and assay for quality evaluation and characterization of tablets of five different brands of Bangladeshi pharmaceutical company. The specified compendial method was followed for their evaluation test. RESULTS: Esomeprazole Mg tablets are enteric coated tablet, there was no disintegration for any brand occurred in 0.1 N HCl after 2 h and all tablets were disintegrated within 19.93 ± 0.04 to 29.05 ± 0.14 min in phosphate buffer (pH 6.8). Weight variation and Hardness were between 1.01 ± 0.29 to 2.01 ± 0.14% and 5.32 ± 0.06 to 7.12 ± 0.12 kgf respectively. Medicine released after 2 h in 0.1 N HCl were varied from 2.55 ± 0.24 to 4.47 ± 0.31% which was less than 10% and in phosphate buffer (pH 6.8) the percentage of medicine release were between 100.9 and 105.9% after 60 min. In case of assay the results of all brands were between 95.28 ± 0.08 and 99.40 ± 0.11%. The obtained results of all parameters were complied with pharmacopoeial limit. So from this study we can conclude that products of esomeprazole available in Bangladeshi pharmaceutical market meet the quality parameter to satisfy therapeutic efficacy.