Massilia agrisoli sp. nov., isolated from rhizospheric soil of banana.

A Gram-stain-negative, aerobic, short rod-shaped and motile novel bacterial strain, designated MAHUQ-52T, was isolated from the rhizospheric soil of a banana plant. Colonies grew at 10-35 °C (optimum, 28 °C), pH 6.0-9.5 (optimum, pH 7.0-7.5), and in the presence of 0-1.0 % NaCl (optimum 0 %). The strain was positive for catalase and oxidase tests, as well as hydrolysis of gelatin, casein, starch and Tween 20. Based on the results of phylogenetic analysis using 16S rRNA gene and genome sequences, strain MAHUQ-52T clustered together within the genus Massilia. Strain MAHUQ-52T was closely related to Massilia soli R798T (98.6 %) and Massilia polaris RP-1-19T (98.3 %). The novel strain MAHUQ-52T has a draft genome size of 4 677 454 bp (25 contigs), annotated with 4193 protein-coding genes, 64 tRNA and 19 rRNA genes. The genomic DNA G+C content was 63.0 %. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between strain MAHUQ-52T and closely related type strains were ≤88.4 and 35.8 %, respectively. The only respiratory quinone was ubiquinone-8. The major fatty acids were identified as C16 : 0 and summed feature 3 (C15 : 0 iso 2-OH and/or C16 : 1 ω7c). Strain MAHUQ-52T contained phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol as the major polar lipids. On the basis of dDDH and ANI values, as well as genotypic, chemotaxonomic and physiological data, strain MAHUQ-52T represents a novel species within the genus Massilia, for which the name Massilia agrisoli sp. nov. is proposed, with MAHUQ-52T (=KACC 21999T=CGMCC 1.18577T) as the type strain.

Fighting Antibiotic Resistance: New Pyrimidine-Clubbed Benzimidazole Derivatives as Potential DHFR Inhibitors.

The present work describes the design and development of seventeen pyrimidine-clubbed benzimidazole derivatives as potential dihydrofolate reductase (DHFR) inhibitors. These compounds were filtered by using ADMET, drug-likeness characteristics calculations, and molecular docking experiments. Compounds 27, 29, 30, 33, 37, 38, and 41 were chosen for the synthesis based on the results of the in silico screening. Each of the synthesized compounds was tested for its in vitro antibacterial and antifungal activities using a variety of strains. All the compounds showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus and Staphylococcus pyogenes) as well as Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Most of the compounds either had a higher potency than chloramphenicol or an equivalent potency to ciprofloxacin. Compounds 29 and 33 were effective against all the bacterial and fungal strains. Finally, the 1,2,3,4-tetrahydropyrimidine-2-thiol derivatives with a 6-chloro-2-(chloromethyl)-1H-benzo[d]imidazole moiety are potent enough to be considered a promising lead for the discovery of an effective antibacterial agent.

Coumarin-Based Sulfonamide Derivatives as Potential DPP-IV Inhibitors: Pre-ADME Analysis, Toxicity Profile, Computational Analysis, and In Vitro Enzyme Assay.

Recent research on dipeptidyl peptidase-IV (DPP-IV) inhibitors has made it feasible to treat type 2 diabetes mellitus (T2DM) with minimal side effects. Therefore, in the present investigation, we aimed to discover and develop some coumarin-based sulphonamides as potential DPP-IV inhibitors in light of the fact that molecular hybridization of many bioactive pharmacophores frequently results in synergistic activity. Each of the proposed derivatives was subjected to an in silico virtual screening, and those that met all of the criteria and had a higher binding affinity with the DPP-IV enzyme were then subjected to wet lab synthesis, followed by an in vitro biological evaluation. The results of the pre-ADME and pre-tox predictions indicated that compounds 6e, 6f, 6h, and 6m to 6q were inferior and violated the most drug-like criteria. It was observed that 6a, 6b, 6c, 6d, 6i, 6j, 6r, 6s, and 6t displayed less binding free energy (PDB ID: 5Y7H) than the reference inhibitor and demonstrated drug-likeness properties, hence being selected for wet lab synthesis and the structures being confirmed by spectral analysis. In the in vitro enzyme assay, the standard drug Sitagliptin had an IC50 of 0.018 µM in the experiment which is the most potent. All the tested compounds also displayed significant inhibition of the DPP-IV enzyme, but 6i and 6j demonstrated 10.98 and 10.14 µM IC50 values, respectively, i.e., the most potent among the synthesized compounds. Based on our findings, we concluded that coumarin-based sulphonamide derivatives have significant DPP-IV binding ability and exhibit optimal enzyme inhibition in an in vitro enzyme assay.

A renewed concept on the MAPK signaling pathway in cancers: Polyphenols as a choice of therapeutics.

Abnormalities in the mitogen-activated protein kinase (MAPK) signaling pathway are a key contributor to the carcinogenesis process and have therefore been implicated in several aspects of tumorigenesis, including cell differentiation, proliferation, invasion, angiogenesis, apoptosis, and metastasis. This pathway offers multiple molecular targets that may be modulated for anticancer activity and is of great interest for several malignancies. Polyphenols from various dietary sources have been observed to interfere with certain aspects of this pathway and consequently play a substantial role in the development and progression of cancer by suppressing cell growth, inactivating carcinogens, blocking angiogenesis, causing cell death, and changing immunity. A good number of polyphenolic compounds have shown promising outcomes in numerous pieces of research and are currently being investigated clinically to treat cancer patients. The current study concentrates on the role of the MAPK pathway in the development and metastasis of cancer, with particular emphasis on dietary polyphenolic compounds that influence the different MAPK sub-pathways to obtain an anticancer effect. This study aims to convey an overview of the various aspects of the MAPK pathway in cancer development and invasion, as well as a review of the advances achieved in the development of polyphenols to modulate the MAPK signaling pathway for better treatment of cancer.

Citrus limon L. (lemon) seed extract shows neuro-modulatory activity in an in vivo thiopental-sodium sleep model by reducing the sleep onset and enhancing the sleep duration.

Citrus limon L. is an ingenious alternative medication and has a broad scope in managing several health conditions as part of natural remedies. Recently, medicinal plants have witnessed incredible consideration worldwide in the field of neuroscience for remedial intervention. The present work has investigated the phytochemical compounds and neuropharmacological potential of the seed extract of Citrus limon as a step to partially validate its formulations as nutraceuticals using an in vivo model. Diverse phytochemical groups such as alkaloids, glycosides, flavonoids, tannins, gums, saponins, steroids were qualitatively identified through colorimetric methods utilizing standard compounds. The neuropharmacological properties were studied in Swiss albino mice with the sleep time induced by thiopental sodium taken as an end-point, in standard hole cross, hole board, and open-field experiments at varying doses of 50 and 100 mg/kg body weight. Phytochemical screening showed that alkaloids, flavonoids, saponins, tannins, steroids, and glycosides are present in the aqueous extract of the seed. The extracts demonstrated a significant reduction in sleep onset and enhanced the sleep duration in a dose-dependent manner in thiopental sodium-induced sleeping time, along with a marked decrease in unconstrained locomotors and explorative properties in both hole cross and open field tests. Moreover, in the hole board study, the extracts minimized the count of head dips observed in the treated mice. The results shown in this study demonstrate that Citrus limon extracts have neuropharmacological properties that can be further examined for their potential role as an adjuvant with conventional medications or nutraceuticals.

The Multifunctional Role of Herbal Products in the Management of Diabetes and Obesity: A Comprehensive Review.

Obesity and diabetes are the most demanding health problems today, and their prevalence, as well as comorbidities, is on the rise all over the world. As time goes on, both are becoming big issues that have a big impact on people's lives. Diabetes is a metabolic and endocrine illness set apart by hyperglycemia and glucose narrow-mindedness because of insulin opposition. Heftiness is a typical, complex, and developing overall wellbeing worry that has for quite some time been connected to significant medical issues in individuals, all things considered. Because of the wide variety and low adverse effects, herbal products are an important hotspot for drug development. Synthetic compounds are not structurally diverse and lack drug-likeness properties. Thus, it is basic to keep on exploring herbal products as possible wellsprings of novel drugs. We conducted this review of the literature by searching Scopus, Science Direct, Elsevier, PubMed, and Web of Science databases. From 1990 until October 2021, research reports, review articles, and original research articles in English are presented. It provides top to bottom data and an examination of plant-inferred compounds that might be utilized against heftiness or potentially hostile to diabetes treatments. Our expanded comprehension of the systems of activity of phytogenic compounds, as an extra examination, could prompt the advancement of remedial methodologies for metabolic diseases. In clinical trials, a huge number of these food kinds or restorative plants, as well as their bioactive compounds, have been shown to be beneficial in the treatment of obesity.

Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint.

Breast cancer (BrCa) is the most common malignancy in women and the second most significant cause of death from cancer. BrCa is one of the most challenging malignancies to treat, and it accounts for a large percentage of cancer-related deaths. The number of cases requiring more effective BrCa therapy has increased dramatically. Scientists are looking for more productive agents, such as organic combinations, for BrCa prevention and treatment because most chemotherapeutic agents are linked to cancer metastasis, the resistance of the drugs, and side effects. Natural compounds produced by living organisms promote apoptosis and inhibit metastasis, slowing the spread of cancer. As a result, these compounds may delay the spread of BrCa, enhancing survival rates and reducing the number of deaths caused by BrCa. Several natural compounds inhibit BrCa production while lowering cancer cell proliferation and triggering cell death. Natural compounds, in addition to therapeutic approaches, are efficient and potential agents for treating BrCa. This review highlights the natural compounds demonstrated in various studies to have anticancer properties in BrCa cells. Future research into biological anti-BrCa agents may pave the way for a new era in BrCa treatment, with natural anti-BrCa drugs playing a key role in improving BrCa patient survival rates.

Natural Small Molecules in Gastrointestinal Tract and Associated Cancers: Molecular Insights and Targeted Therapies.

Gastric cancer is one of the most common cancers of the gastrointestinal tract. Although surgery is the primary treatment, serious maladies that dissipate to other parts of the body may require chemotherapy. As there is no effective procedure to treat stomach cancer, natural small molecules are a current focus of research interest for the development of better therapeutics. Chemotherapy is usually used as a last resort for people with advanced stomach cancer. Anti-colon cancer chemotherapy has become increasingly effective due to drug resistance and sensitivity across a wide spectrum of drugs. Naturally-occurring substances have been widely acknowledged as an important project for discovering innovative medications, and many therapeutic pharmaceuticals are made from natural small molecules. Although the beneficial effects of natural products are as yet unknown, emerging data suggest that several natural small molecules could suppress the progression of stomach cancer. Therefore, the underlying mechanism of natural small molecules for pathways that are directly involved in the pathogenesis of cancerous diseases is reviewed in this article. Chemotherapy and molecularly-targeted drugs can provide hope to colon cancer patients. New discoveries could help in the fight against cancer, and future stomach cancer therapies will probably include molecularly formulated drugs.

Virtual Screening, Synthesis, and Biological Evaluation of Some Carbohydrazide Derivatives as Potential DPP-IV Inhibitors.

Dipeptidyl peptidase-4 (DPP-IV) inhibitors are known as safe and well-tolerated antidiabetic medicine. Therefore, the aim of the present work was to synthesize some carbohydrazide derivatives (1a-5d) as DPP-IV inhibitors. In addition, this work involves simulations using molecular docking, ADMET analysis, and Lipinski and Veber's guidelines. Wet-lab synthesis was used to make derivatives that met all requirements, and then FTIR, NMR, and mass spectrometry were used to confirm the structures and perform biological assays. In this context, in vitro enzymatic and in vivo antidiabetic activity evaluations were carried out. None of the molecules had broken the majority of the drug-likeness rules. Furthermore, these molecules were put through additional screening using molecular docking. In molecular docking experiments (PDB ID: 2P8S), many molecules displayed more potent interactions than native ligands, exhibiting more hydrogen bonds, especially those with chloro- or fluoro substitutions. Our findings indicated that compounds 5b and 4c have IC50 values of 28.13 and 34.94 µM, respectively, under in vitro enzymatic assays. On the 21st day of administration to animals, compound 5b exhibited a significant reduction in serum blood glucose level (157.33 ± 5.75 mg/dL) compared with the diabetic control (Sitagliptin), which showed 280.00 ± 13.29 mg/dL. The antihyperglycemic activity showed that the synthesized compounds have good hypoglycemic potential in fasting blood glucose in the type 2 diabetes animal model (T2DM). Taken all together, our findings indicate that the synthesized compounds exhibit excellent hypoglycemic potential and could be used as leads in developing novel antidiabetic agents.

Pectin: A Bioactive Food Polysaccharide with Cancer Preventive Potential.

Pectin is an acidic heteropolysaccharide found in the cell walls and the primary and middle lamella of land plants. To be authorized as a food additive, industrial pectins must meet strict guidelines set forth by the Food and Agricultural Organization and must contain at least 65% polygalacturonic acid to achieve the E440 level. Fruit pectin derived from oranges or apples is commonly used in the food industry to gel or thicken foods and to stabilize acid-based milk beverages. It is a naturally occurring component and can be ingested by dietary consumption of fruit and vegetables. Preventing long-term chronic diseases like diabetes and heart disease is an important role of dietary carbohydrates. Colon and breast cancer are among the diseases for which data suggest that modified pectin (MP), specifically modified citrus pectin (MCP), has beneficial effects on the development and spread of malignancies, in addition to its benefits as a soluble dietary fiber. Cellular and animal studies and human clinical trials have provided corroborating data. Although pectin has many diverse functional qualities, this review focuses on various modifications used to develop MP and its benefits for cancer prevention, bioavailability, clinical trials, and toxicity studies. This review concludes that pectin has anti-cancer characteristics that have been found to inhibit tumor development and proliferation in a wide variety of cancer cells. Nevertheless, further clinical and basic research is required to confirm the chemopreventive or therapeutic role of specific dietary carbohydrate molecules.

Natural Bioactive Molecules: An Alternative Approach to the Treatment and Control of COVID-19.

Several coronaviruses (CoVs) have been associated with serious health hazards in recent decades, resulting in the deaths of thousands around the globe. The recent coronavirus pandemic has emphasized the importance of discovering novel and effective antiviral medicines as quickly as possible to prevent more loss of human lives. Positive-sense RNA viruses with group spikes protruding from their surfaces and an abnormally large RNA genome enclose CoVs. CoVs have already been related to a range of respiratory infectious diseases possibly fatal to humans, such as MERS, SARS, and the current COVID-19 outbreak. As a result, effective prevention, treatment, and medications against human coronavirus (HCoV) is urgently needed. In recent years, many natural substances have been discovered with a variety of biological significance, including antiviral properties. Throughout this work, we reviewed a wide range of natural substances that interrupt the life cycles for MERS and SARS, as well as their potential application in the treatment of COVID-19.

The Multifaceted Role of Curcumin in Advanced Nanocurcumin Form in the Treatment and Management of Chronic Disorders.

Curcumin is the primary polyphenol in turmeric's curcuminoid class. It has a wide range of therapeutic applications, such as anti-inflammatory, antioxidant, antidiabetic, hepatoprotective, antibacterial, and anticancer effects against various cancers, but has poor solubility and low bioavailability. Objective: To improve curcumin's bioavailability, plasma concentration, and cellular permeability processes. The nanocurcumin approach over curcumin has been proven appropriate for encapsulating or loading curcumin (nanocurcumin) to increase its therapeutic potential. Conclusion: Though incorporating curcumin into nanocurcumin form may be a viable method for overcoming its intrinsic limitations, and there are reasonable concerns regarding its toxicological safety once it enters biological pathways. This review article mainly highlights the therapeutic benefits of nanocurcumin over curcumin.

Polyphenols as Therapeutics in Respiratory Diseases: Moving from Preclinical Evidence to Potential Clinical Applications.

Respiratory diseases are the most common and severe health complication and a leading cause of death worldwide. Despite breakthroughs in diagnosis and treatment, few safe and effective therapeutics have been reported. Phytochemicals are gaining popularity due to their beneficial effects and low toxicity. Polyphenols are secondary metabolites with high molecular weights found at high levels in natural food sources such as fruits, vegetables, grains, and citrus seeds. Over recent decades, polyphenols and their beneficial effects on human health have been the subject of intense research, with notable successes in preventing major chronic non-communicable diseases. Many respiratory syndromes can be treated effectively with polyphenolic supplements, including acute lung damage, pulmonary fibrosis, asthma, pulmonary hypertension, and lung cancer. This review summarizes the role of polyphenols in respiratory conditions with sufficient experimental data, highlights polyphenols with beneficial effects for each, and identifies those with therapeutic potential and their underlying mechanisms. Moreover, clinical studies and future research opportunities in this area are discussed.

Indole alkaloids from marine resources: Understandings from therapeutic point of view to treat cancers.

Cancer is the leading cause of mortality all over the world. Scientific investigation has demonstrated that disruptions in the process of autophagy are frequently interrelated with the emergence of cancer. Hence, scientists are seeking permanent solutions to counter the deadly disease. Indole alkaloids have been extensively studied and are acknowledged to exhibit several bioactivities. The current state of disease necessitates novel pharmacophores development. In recent decades, indole alkaloids have become increasingly significant in cancer treatment and are also used as adjuvants. A substantial amount of pharmacologically active molecules come from indole alkaloids, which are widely distributed in nature. Indole alkaloids derived from marine organisms show immense potential for therapeutic applications and seem highly effective in cancer treatment. A couple of experiments have been conducted preclinically to investigate the possibility of indole alkaloids in cancer treatment. Marine-derived indole alkaloids possess the ability to exhibit anticancer properties through diverse antiproliferative mechanisms. Certain indole alkaloids, including vincristine and vinblastine, were verified in clinical trials or are presently undergoing clinical assessments for preventing and treating cancer. Indole alkaloids from marine resources hold a significant functionality in identifying new antitumor agents. The current literature highlights recent advancements in indole alkaloids that appear to be anticancer agents and the underlying mechanisms.

Emerging Promise of Therapeutic Approaches Targeting Mitochondria in Neurodegenerative Disorders.

Mitochondria are critical for homeostasis and metabolism in all cellular eukaryotes. Brain mitochondria are the primary source of fuel that supports many brain functions, including intracellular energy supply, cellular calcium regulation, regulation of limited cellular oxidative capacity, and control of cell death. Much evidence suggests that mitochondria play a central role in neurodegenerative disorders (NDDs) such as Parkinson's disease, Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis. Ongoing studies of NDDs have revealed that mitochondrial pathology is mainly found in inherited or irregular NDDs and is thought to be associated with the pathophysiological cycle of these disorders. Typical mitochondrial disturbances in NDDs include increased free radical production, decreased ATP synthesis, alterations in mitochondrial permeability, and mitochondrial DNA damage. The main objective of this review is to highlight the basic mitochondrial problems that occur in NDDs and discuss the use mitochondrial drugs, especially mitochondrial antioxidants, mitochondrial permeability transition blockade, and mitochondrial gene therapy, for the treatment and control of NDDs.

Polyphenols Targeting MAP Kinase Signaling Pathway in Neurological Diseases: Understanding Molecular Mechanisms and Therapeutic Targets.

Polyphenols are a class of secondary metabolic products found in plants that have been extensively studied for how well they regulate biological processes, such as the proliferation of cells, autophagy, and apoptosis. The mitogen-activated protein kinase (MAPK)-mediated signaling cascade is currently identified as a crucial pro-inflammatory pathway that plays a significant role in the development of neuroinflammation. This process has been shown to contribute to the pathogenesis of several neurological conditions, such as Alzheimer's disease (AD), Parkinson's disease (PD), CNS damage, and cerebral ischemia. Getting enough polyphenols through eating habits has resulted in mitigating the effects of oxidative stress (OS) and lowering the susceptibility to associated neurodegenerative disorders, including but not limited to multiple sclerosis (MS), AD, stroke, and PD. Polyphenols possess significant promise in dealing with the root cause of neurological conditions by modulating multiple therapeutic targets simultaneously, thereby attenuating their complicated physiology. Several polyphenolic substances have demonstrated beneficial results in various studies and are presently undergoing clinical investigation to treat neurological diseases (NDs). The objective of this review is to provide a comprehensive summary of the different aspects of the MAPK pathway involved in neurological conditions, along with an appraisal of the progress made in using polyphenols to regulate the MAPK signaling system to facilitate the management of NDs.

Exploring the role of natural bioactive molecules in genitourinary cancers: how far has research progressed?

The primary approaches to treat cancerous diseases include drug treatment, surgical procedures, biotherapy, and radiation therapy. Chemotherapy has been the primary treatment for cancer for a long time, but its main drawback is that it kills cancerous cells along with healthy ones, leading to deadly adverse health effects. However, genitourinary cancer has become a concern in recent years as it is more common in middle-aged people. So, researchers are trying to find possible therapeutic options from natural small molecules due to the many drawbacks associated with chemotherapy and other radiation-based therapies. Plenty of research was conducted regarding genitourinary cancer to determine the promising role of natural small molecules. So, this review focused on natural small molecules along with their potential therapeutic targets in the case of genitourinary cancers such as prostate cancer, renal cancer, bladder cancer, testicular cancer, and so on. Also, this review states some ongoing or completed clinical evidence in this regard.

Genus Amorphophallus: A Comprehensive Overview on Phytochemistry, Ethnomedicinal Uses, and Pharmacological Activities.

The genus Amorphophallus belongs to the family Araceae. Plants belonging to this genus are available worldwide and have been used in traditional medicines since ancient times, mainly in Ayurveda and Unani medical practices. Amorphophallus species are an abundant source of polyphenolic compounds; these are accountable for their pharmacological properties, such as their analgesic, neuroprotective, hepatoprotective, anti-inflammatory, anticonvulsant, antibacterial, antioxidant, anticancer, antiobesity, and immunomodulatory effects, as well as their ability to prevent gastrointestinal disturbance and reduce blood glucose. Moreover, Amorphophallus species contain numerous other classes of chemical compounds, such as alkaloids, steroids, fats and fixed oils, tannins, proteins, and carbohydrates, each of which contributes to the pharmacological effects for the treatment of acute rheumatism, tumors, lung swelling, asthma, vomiting, abdominal pain, and so on. Additionally, Amorphophallus species have been employed in numerous herbal formulations and pharmaceutical applications. There has been no extensive review conducted on the Amorphophallus genus as of yet, despite the fact that several experimental studies are being published regularly discussing these plants' pharmacological properties. So, this review discusses in detail the pharmacological properties of Amorphophallus species. We also discuss phytochemical constituents in the Amorphophallus species and their ethnomedicinal uses and toxicological profiles.

Natural polymers as potential P-glycoprotein inhibitors: Pre-ADMET profile and computational analysis as a proof of concept to fight multidrug resistance in cancer.

P-glycoprotein (P-gp) is known as the "multidrug resistance protein" because it contributes to tumor resistance to several different classes of anticancer drugs. The effectiveness of such polymers in treating cancer and delivering drugs has been shown in a wide range of in vitro and in vivo experiments. The primary objective of the present study was to investigate the inhibitory effects of several naturally occurring polymers on P-gp efflux, as it is known that P-gp inhibition can impede the elimination of medications. The objective of our study is to identify polymers that possess the potential to inhibit P-gp, a protein involved in drug resistance, with the aim of enhancing the effectiveness of anticancer drug formulations. The ADMET profile of all the selected polymers (Agarose, Alginate, Carrageenan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid) has been studied, and binding affinities were investigated through a computational approach using the recently released crystal structure of P-gp with PDB ID: 7O9W. The advanced computational study was also done with the help of molecular dynamics simulation. The aim of the present study is to overcome MDR resulting from the activity of P-gp by using such polymers that can inhibit P-gp when used in formulations. The docking scores of native ligand, Agarose, Alginate, Carrageenan, Chitosan, Cyclodextrin, Dextran, Hyaluronic acid, and Polysialic acid were found to be -10.7, -8.5, -6.6, -8.7, -8.6, -24.5, -6.7, -8.3, and -7.9, respectively. It was observed that, Cyclodextrin possess multiple properties in drug delivery science and here also demonstrated excellent binding affinity. We propose that drug efflux-related MDR may be prevented by the use of Agarose, Carregeenan, Chitosan, Cyclodextrin, Hyaluronic acid, and/or Polysialic acid in the administration of anticancer drugs.