Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules.

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.

Synthesis and evaluation of nanosized aluminum MOF encapsulating Umbelliferon: assessing antioxidant, anti-inflammatory, and wound healing potential in an earthworm model.

Nanoporous aluminum metal-organic framework (Al-MOF) was synthesized via solvothermal methods and employed as a carrier matrix for in vitro drug delivery of Umbelliferon (Um). The encapsulated Um was gradually released over seven days at 37 °C, using simulated body fluid phosphate-buffered saline (PBS) at pH 7.4 as the release medium. The drug release profile suggests the potential of Al-MOF nanoparticles as effective drug delivery carriers. Structural and chemical analyses of Um-loaded Al-MOF nanoparticles (Um-Al MOF) were conducted using Fourier-transform infrared (FTIR) spectroscopy, X-ray diffractometry (XRD), and ultraviolet-visible (UV-Vis) spectroscopy. Thermal gravimetric analysis (TGA) was employed to investigate the thermal stability of the Al-MOF nanoparticles, while Transmission Electron Microscopy (TEM) was utilized to assess their morphological features. Um-Al MOF nanoparticles demonstrated notable antioxidant and anti-inflammatory properties compared to Um and Al-MOF nanoparticles individually. Moreover, they exhibited significant enhancement in wound healing in an earthworm model. These findings underscore the potential of Al-MOF nanoparticles as a promising drug delivery system, necessitating further investigations to explore their clinical applicability.

Finger millet (Eleusine coracana L.): from staple to superfood-a comprehensive review on nutritional, bioactive, industrial, and climate resilience potential.

MAIN CONCLUSION: This review discusses the Finger millet's rich nutritional profile, bioactive potential, and industrial applications, combined with its climate resilience, which make it a promising crop for enhancing food security and promoting sustainable agriculture. This review also highlights its significant potential to address malnutrition and mitigate climate change impacts. The emergence of Finger millet from "poor man's staple food" to "a nutrient rich cereal" has encouraged the need to explore this crop at a wider scale. It is a highly significant crop due to its rich nutritional and bioactive profile, diverse biological activities, and promising industrial applications, along with the high climate resilience. This comprehensive review evaluates its nutritional composition by comparing favorably with other cereals and millets and emphasizing its potential to address malnutrition and enhance food security. Furthermore, it explores the phytochemical/bioactive potential and strategies to enhance their bioavailability followed biological activities of Finger millet by highlighting its various health-promoting properties. The review also discusses industrial potential of finger millet including its role in nutraceutical and functional food production, as well as bioenergy generation. In addition, role of Finger millet as a climate-resilient crop; specifically, the available genetic resources and identification of genes and quantitative trait loci (QTLs) associated with major stress tolerance traits have also been discussed. By providing a comprehensive synthesis of existing knowledge, this study offers valuable insights for researchers, policymakers, and stakeholders engaged in efforts to promote sustainable agriculture, enhance food and nutrition security, and mitigate the impacts of climate change.

The hidden treasures in endophytic fungi: a comprehensive review on the diversity of fungal bioactive metabolites, usual analytical methodologies, and applications.

This review provides a comprehensive overview of the key aspects of the natural metabolite production by endophytic fungi, which has attracted significant attention due to its diverse biological activities and wide range of applications. Synthesized by various fungal species, these metabolites encompass compounds with therapeutic, agricultural, and commercial significance. We delved into strategies and advancements aimed at optimizing fungal metabolite production. Fungal cultivation, especially by Aspergillus, Penicillium, and Fusarium, plays a pivotal role in metabolite biosynthesis, and researchers have explored both submerged and solid-state cultivation processes to harness the full potential of fungal species. Nutrient optimization, pH, and temperature control are critical factors in ensuring high yields of the targeted bioactive metabolites especially for scaling up processes. Analytical methods that includes High-Performance Liquid Chromatography (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), Gas Chromatography-Mass Spectrometry (GC-MS), Nuclear Magnetic Resonance (NMR), and Mass Spectrometry (MS), are indispensable for the identification and quantification of the compounds. Moreover, genetic engineering and metabolic pathway manipulation have emerged as powerful tools to enhance metabolite production and develop novel fungal strains with increased yields. Regulation and control mechanisms at the genetic, epigenetic, and metabolic levels are explored to fine-tune the biosynthesis of fungal metabolites. Ongoing research aims to overcome the complexity of the steps involved to ensure the efficient production and utilization of fungal metabolites.

The function and application of edible fungal polysaccharides.

Edible fungi, commonly known as mushrooms, are precious medicinal and edible homologous gifts from nature to us. Edible fungal polysaccharides (EFPs) are a variety of bioactive macromolecular which isolated from fruiting bodies, mycelia or fermentation broths of edible or medicinal fungus. Increasing researches have confirmed that EFPs possess multiple biological activities both in vitro and in vivo settings, including antioxidant, antiviral, anti-inflammatory, immunomodulatory, anti-tumor, hypoglycemic, hypolipidemic, and regulating intestinal flora activities. As a result, they have emerged as a prominent focus in the healthcare, pharmaceutical, and cosmetic industries. Fungal EFPs have safe, non-toxic, biodegradable, and biocompatible properties with low immunogenicity, bioadhesion ability, and antibacterial activities, presenting diverse potential applications in the food industries, cosmetic, biomedical, packaging, and new materials. Moreover, varying raw materials, extraction, purification, chemical modification methods, and culture conditions can result in variances in the structure and biological activities of EFPs. The purpose of this review is to provide comprehensively and systematically organized information on the structure, modification, biological activities, and potential applications of EFPs to support their therapeutic effects and health functions. This review provides new insights and a theoretical basis for prospective investigations and advancements in EFPs in fields such as medicine, food, and new materials.

Current development and structure-activity relationship study of berberine derivatives.

Berberine is a quaternary ammonium isoquinoline alkaloid derived from traditional Chinese medicines Coptis chinensis and Phellodendron chinense. It has many pharmacological activities such as hypoglycemic, hypolipidemic, anti-tumor, antimicrobial and anti-inflammatory. Through structural modifications at various sites of berberine, the introduction of different groups can change berberine's physical and chemical properties, thereby improving the biological activity and clinical efficacy, and expanding the scope of application. This paper reviews the research progress and structure-activity relationships of berberine in recent years, aiming to provide valuable insights for the exploration of novel berberine derivatives.

A Comprehensive on Synthesis and Antimicrobial Evaluation of Substituted-Arylideneamino-5-(5-Chlorobenzofuran-2-yl)-1, 2, 4-Triazole-3-Thiol Derivatives/ Schiff Bases.

Schiff bases are well known and popular classes of organic compounds containing imine (R2C = NH) group that are widely used as catalysts and intermediates in numerous organic transformations. Schiff bases are medicinally very important because they exhibit antimicrobial like antibacterial, antiviral and anticancer activities. Benzofuran based Schiff bases have been found as interesting scaffolds for the synthesis and design of biologically active agents. Moreover, they possess a wide range of biological activities against fungal, bacterial, malarial, inflammatory and viral diseases. In this reviw, substituted-arylideneamino-5-(5-chlorobenzofuran-2-yl)-1,2,4-triazole-3-thiols have been synthesized by using efficient synthetic protocols. The synthesized derivatives are also evaluated against different bacterial strains.

Biologically active isoquinoline alkaloids covering 2019-2022.

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.

Dibenzofurans from nature: Biosynthesis, structural diversity, sources, and bioactivities.

Dibenzofurans are a small class of natural products with versatile biological activities that used to be thought to come mainly from lichens and ascomycetes. In fact, they are also distributed widely in higher plants, especially in the families Rosaceae and Myrtaceae. Dibenzofurans and derivatives from lichens and ascomycetes have been well reviewed, but dibenzofurans from all biological sources in nature have not been reviewed. In this review, dibenzofurans from all natural sources have been comprehensively reviewed, and a total of 211 dibenzofurans isolated and identified from organisms between 1843 and March 2023 are categorized and discussed, including their biosynthesis, structural diversity, sources, and bioactivities.

Identification of new anti-mycobacterial agents based on quinoline-isatin hybrids targeting enoyl acyl carrier protein reductase (InhA).

Tuberculosis (TB) is a global issue that poses a significant economic burden as a result of the ongoing emergence of drug-resistant strains. The urgent requirement for the development of novel antitubercular drugs can be addressed by targeting specific enzymes. One such enzyme, Mycobacterium tuberculosis (MTB) enoyl-acyl carrier protein (enoyl-ACP) reductase (InhA), plays a crucial role in the survival of the MTB bacterium. In this research study, a series of hybrid compounds combining quinolone and isatin were synthesized and assessed for their effectiveness against MTB, as well as their ability to inhibit the activity of the InhA enzyme in this bacterium. Among the compounds tested, 7a and 5g exhibited the most potent inhibitory activity against MTB, with minimum inhibitory concentration (MIC) values of 55 and 62.5 µg/mL, respectively. These compounds were further evaluated for their inhibitory effects on InhA and demonstrated significant activity compared to the reference drug Isoniazid (INH), with IC50 values of 0.35 ± 0.01 and 1.56 ± 0.06 µM, respectively. Molecular docking studies investigated the interactions between compounds 7a and 5g and the target enzyme, revealing hydrophobic contacts with important amino acid residues in the active site. To further confirm the stability of the complexes formed by 5g and 7a with the target enzyme, molecular dynamic simulations were employed, which demonstrated that both compounds 7a and 5g undergo minor structural changes and remain nearly stable throughout the simulated process, as assessed through RMSD, RMSF, and Rg values.

An overview of recent advancements in small molecules suppression of oncogenic signaling of K-RAS: an updated review.

RAS (rat sarcoma) oncoproteins are crucial for the growth of some human cancers, including lung, colorectal, and pancreatic adenocarcinomas. The RAS family contains three known human isoforms H(Harvey)-RAS, N(Neuroblastoma)-RAS, and K(Kirsten)-RAS. Mutations in RAS proteins cause up to ~ 30% of cancer cases. For almost 30 years, mutant proteins druggable pockets remained undiscovered, they are nearly identical to their essential, wild-type counterparts and cause cancer. Recent research has increased our knowledge of RAS's structure, processing, and signaling pathways and revealed novel insights into how it works in cancer cells. We highlight several approaches that inhibit RAS activity with small compounds in this review: substances that blocked farnesyltransferase (FTase), isoprenylcysteine carboxyl methyltransferase (Icmt), and RAS-converting enzyme 1 (Rce1) three important enzymes required for RAS localization. Inhibitors block the son of sevenless (SOS) protein's role in nucleotide exchange activity, small molecules that interfered with the phosphodiesterase (PDEδ)-mediated intracellular RAS transport processes, substances that focused on inhibiting RAS-effector interactions. Inhibitors are made to suppress the oncogenic K-RAS G12C mutant only when the nucleophilic cysteine residue at codon 12 is present and many inhibitors with various mechanisms like breaking the organization membrane of K-RAS nano-clustering. So, this is a thorough analysis of the most recent advancements in K-RAS-targeted anticancer techniques, hopefully offering insight into the field's future.

Defining the mechanisms behind the hepatoprotective properties of curcumin.

As a critical cause of human dysfunctionality, hepatic failure leads to approximately two million deaths per year and is on the rise. Considering multiple inflammatory, oxidative, and apoptotic mechanisms behind hepatotoxicity, it urges the need for finding novel multi-targeting agents. Curcumin is a phenolic compound with anti-inflammatory, antioxidant, and anti-apoptotic roles. Curcumin possesses auspicious health benefits and protects against several diseases with exceptional safety and tolerability. This review focused on the hepatoprotective mechanisms of curcumin. The need to develop novel delivery systems of curcumin (e.g., nanoparticles, self-micro emulsifying, lipid-based colloids, solid lipid nanoparticles, cyclodextrin inclusion, phospholipid complexes, and nanoemulsions) is also considered.

Luteolin: A promising multifunctional natural flavonoid for human diseases.

Natural products are closely associated with human health. Luteolin (LUT), a flavonoid polyphenolic compound, is widely found in fruits, vegetables, flowers, and herbs. It is noteworthy that LUT exhibits a variety of beneficial pharmacological properties and holds significant potential for clinical applications, particularly in antitumor, anti-convulsion, diabetes control, anti-inflammatory, neuroprotection, anti-oxidation, anti-cardiovascular, and other aspects. The potential mechanism of action has been partially elucidated, including the mediation of NF-κB, toll-like receptor, MAPK, Wnt/ß-catenin, PI3K/Akt, AMPK/mTOR, and Nrf-2, among others. The review that aimed to comprehensively consolidate essential information on natural sources, pharmacological effects, therapeutic and preventive potential, as well as potential mechanisms of LUT. The objective is to establish a theoretical basis for the continued development and application of LUT.

Abietane-Type Diterpenoids: Insights into Structural Diversity and Therapeutic Potential.

The abietane-type diterpenoids are among the most significant diterpene subsets found in hundreds of plant species belonging to various families. Among which, the members of the genus Salvia and Euphorbia are rich in abietane diterpenoids. Because of the chemical diversity and notable bioactivities, such as anticancer, antiinflammatory, antimicrobial, and antioxidant activities, they are attractive. Herein, recent advances in the isolation and characterization of abietanes from natural sources, as well as their biological activities, from 2015 up to 2024 are reviewed. During this time, over 300 abietanes with diverse structures have been discovered.

Biological Properties of Cyclitols and Their Derivatives.

Cyclitols are polyhydroxy cycloalkanes, each containing at least three hydroxyls attached to a different ring carbon atom. The most important cyclitol derivatives are inositols, quercitols, conduritols and pinitols, which form a group of naturally occurring polyhydric alcohols and are widely found in plants. In addition, synthetic production of cyclitols has gained importance in recent years. Cylitols are molecules synthesized in plants as a precaution against salt or water stress. They have important functions in cell functioning as they exhibit important properties such as membrane biogenesis, ion channel physiology, signal transduction, osmoregulation, phosphate storage, cell wall formation and antioxidant activity. The biological activities of these very important molecules, obtained both synthetically and from the extraction of plants, are described in this review.

HPLC/ESI-MS Characterization of Phenolic Compounds from Cnicus benedictus L. Roots: A Study of Antioxidant, Antibacterial, Anti-Inflammatory, and Anti-Alzheimer's Activity.

The phenolic composition of Cnicus benedictus roots from four Algerian regions was investigated. Extractions were performed in both hydro-methanolic (30 : 70, v/v) and hydro-ethanolic (30 : 70, v/v) solvents. Their efficiency was determined in terms of the qualitative and quantitative composition in phenolic compounds by HPLC-LC/MS of the different extracts isolated from C. Benedictus roots. Cnicus benedictus roots extract have been characterized by high content of phenolic compounds, where the trans chalcone, 2,3-dihydro flavone, 3-hydroxy flavone and cinnamic acid constitute the major components, in addition to fourteen minor acidic compounds and flavonoids as rutin. The hydro-methanolic extract was the richest in phenolic compounds yield from C benedictus. On the other hand, hydro methanolic (30 : 70, v/v) and hydro ethanolic (30 : 70, v/v) extracts exhibited a high anti-inflammatory activity by in vitro 5-lipoxygenase inhibitory activity (IC50 : 6.05±94.16 µg/mL) as well as by in silico docking according two methods. Likewise, anti-Alzheimer activity of extracts was confirmed by this last technique taking into account the major compounds identified. Antibacterial tests revealed interesting results compared to amoxicillin for the different regions studied with a high content in trans chalcone and 3-hydroxy Flavone.

Genus Berberis: A Comprehensive and Updated Review on Ethnobotanical Uses, Phytochemistry and Pharmacological Activities.

Genus Berberis is an excellent choice for research due to its history in traditional medicine, diverse pharmacological properties, and it has potential for drug discovery. This review presents information on the ethnobotany, pharmacological activities, and many phytochemicals identified from Berberis species. It examines the existing literature on the genus Berberis, drawn from online databases, including PubMed, Web of Science, Science Direct, Elsevier, and Google Scholar, etc encompassing the data from 1960 to 2023. This review focuses on the structural details of reported phytochemicals of Berberis species and pharmacological actions. Different extraction techniques were evaluated for extracts preparation. According to literature review, phytochemical analysis exhibited the presence of alkaloids, flavonoids, and phenolic compounds. A major bioactive alkaloid, berberine exhibits its main role in treatment of many gastric, infectious, and chronic disorders. This literature indicates that Berberis genus exhibits a variety of biological activities, i.e anti-inflammatory, cytotoxic, hepatoprotective, antimicrobial, antidiabetic and antioxidant activities and utilization of these effects in the treatment and management of various diseases, like diabetes, microbial infections, inflammation, liver disorders, and cancer. However, conventional medicines, validation of traditional uses, and in-depth phytochemical analysis are areas of research in genus Berberis.

Natural Peroxides from Plants: Historical Discovery, Biosynthesis, and Biological Activities.

Naturally occurring peroxides received great interest and attention from scientific research groups worldwide due to their structural diversity, versatile biological activities, and pharmaceutical properties. In the present review, we describe the historical discovery of natural peroxides from plants systematically and update the researchers with recently explored ones justifying their structural caterogrization and biological/pharmaceutical properties intensively. Till the end of 2023, 192 peroxy natural products from plants were documented herein for the first time implying most categories of natural scaffolds (e. g. terpenes, polyketides, phenolics and alkaloids). Numerically, the reported plants' peroxides have been classified into seventy-four hydro-peroxides, hundred seven endo-peroxides and eleven acyl-peroxides. Endo-peroxides (cyclic alkyl peroxides) are an important group due to their high variety of structural frameworks, and we have further divided them into "four-, five-, six and seven"-membered rings. Biosynthetically, a shedding light on the intricate mechanisms behind the formation of plant-derived peroxides are addressed as well.

The Chemistry and Biology of Lycopodium Alkaloids.

Lycopodiales, an order comprising 388 distinct species, is the source of Lycopodium alkaloids (LAs), a group of naturally occurring alkaloids that share a common biosynthesis and structural attributes. These remarkable organisms are considered vestiges of ancient ferns, with fossil evidence dating their existence back to an impressive 300 million years. LAs usually are tricyclic or tetracyclic compounds with C16N or C16N2 skeleton. But then there are also have a few C11N, C15N, C15N2, C22N2, and C27N3 skeleton. LAs have attracted much scientific attention because of their important biological activities related to acetylcholinesterase and unique structural characteristics. From 1881 to December 2023, there are 593 LAs from 49 species of Lycopodiales have been reported. Because the total amount of LAs is nearly five times that of 1994, the classification and group allocation of some newly isolated LAs is often challenging and not unambiguous by Ayer's simple classification. This review makes a more systematic and detailed classification for it and provides extensive coverage of naturally occurring LAs discovered from 1881 to December 2023. Until now, there is no comprehensively summary of biological activity of the LAs. This review is the first time covered the biological activity of the all LAs.

Biomedical Perspectives of Citronellal: Biological Activities, Toxicological Profile and Molecular Mechanisms.

Citronellal, known as rhodinal, is a naturally occurring monoterpenoid aldehyde distinctly found in the distilled oils of Cymbopogon species including C. marginatus, C. citratus, C. validus and C. winterianus family Gramineae. It is also obtained from eucalyptus, mentha, melissa, cinnamomum and allium. It is traditionally used in air freshener, cleaner, floor polishing, deodorants, moisturizing hand/body lotion, perfumes, and adhesives due to its lemon characteristic fragrance and therapeutic benefits. This study aimed to summarize the pharmacological activities and underlying mechanisms of citronellal against different diseases, as well as its toxicological profile. The data was collected from various reliable and authentic literatures by searching different academic search engines, including PubMed, Springer Link, Scopus, Wiley Online, Web of Science, ScienceDirect, and Google Scholar. The findings imply that citronellal demonstrated several pharmacological effects in various preclinical and pharmacological experimental systems. The results indicated that citronellal demonstrated antioxidant, anti-inflammatory, antibacterial, antifungal, anthelminthic, and anticancer effects with beneficial effects in neurological and cardiovascular diseases. Our findings also indicated the toxic level of the phytochemical. In conclusion, it has been proposed that citronellal has the capability to serve as a hopeful therapeutic agent, so further extensive clinical research is necessary to develop it as a reliable drug.