Angucyclines and angucyclinones represent a class of natural compounds that belong to the group of aromatic polyketides. They exhibit a wide array of biological properties, such as antimicrobial, antiviral, and cytotoxic. Their considerable therapeutic potential and diverse scaffolds have attracted many synthetic chemists to devise novel strategies to construct their intricate molecular architecture. Over 300 class members have been isolated from natural sources, mainly from bacterial strains of Streptomyces species. This review highlights recent advancements in their synthesis, such as oxidative cyclization, photooxidation, and metal-catalyzed [4+2]-cycloaddition, which has facilitated the efficient and practical total syntheses of various angucyclines natural products.

For many centuries, traditional medicine has played an essential role in health care. The treatment of many illnesses, including cancer, has greatly benefited from using herbal remedies derived from traditional medicine. The bioactive compounds, such as curcumin, silibinin, berberine, ginseng, and others present in traditional medicine have shown a wide range of properties, such as anti-inflammatory, antimicrobial, anti-oxidant as well as potent anti-cancer properties both in laboratory studies and animal experiments (in vitro and in vivo). In this review, we mainly emphasized the anticancer role of bioactive compounds present in traditional medicine, such as curcumin, cardamonin, piperine, berberine, ginseng, silibinin, epigallocatechin gallate, and asafoetida. We also discussed molecular evidence of these compounds in chemoprevention and anticancer effects. These compounds have the potential to interfere with cancer growth, proliferation, metastasis, and angiogenesis and induce apoptosis by targeting different pathways and the cell cycle. This review article also focuses on how these compounds can help overcome drug resistance and enhance the availability of other clinically approved drugs. The usage of these compounds synergistically with other forms of treatment is also of great fascination to new and upcoming research. Finally, we have discussed the bioavailability of these compounds and strategies employed to improve them so their full potential can be exploited.

Pyr4-family terpene cyclases are noncanonical transmembrane class II terpene cyclases that catalyze a variety of cyclization reactions in the biosynthesis of microbial terpenoids, such as meroterpenoids. However, although these cyclases are widely distributed in microorganisms, their three-dimensional structures have not been determined, possibly due to the transmembrane locations of these enzymes. In this chapter, we describe procedures for the functional analysis of transmembrane terpene cyclases based on their model structures generated using AlphaFold2. We used AdrI, the Pyr4-family terpene cyclase required for the biosynthesis of andrastin A and its homologs, as an example.

Expression and purification of membrane-bound proteins remains a challenge and limits enzymology efforts, contributing to a substantial knowledge gap in the biochemical functions of many proteins found in nature. Accordingly, the study of bacterial UbiA terpene synthases (TSs) has been limited due to the experimental hurdles required to purify active enzymes for characterization in vitro. Previous work employed the use of microsomes or crude membrane fractions to test enzyme activity; however, these methods can be labor intensive, require access to an ultracentrifuge, or may not be suitable for all membrane-bound TSs. We detail here an alternative strategy for the in vivo expression and biochemical characterization of the membrane associated UbiA TSs by employing a precursor overproduction system in Escherichia coli.

Chronic sleep disturbance affects daily functioning, leading to decreased concentration, fatigue, and higher healthcare costs. Traditional insomnia medications are often associated with adverse side effects. This study investigated the efficacy of a novel compound derived from Rhodiola rosea and Nelumbo nucifera extracts (named RNE) in improving sleep quality with fewer side effects. The study included individuals between the ages of 20 and 65 with subthreshold insomnia and evaluated the effects of RNE on sleep, fatigue, and quality of life. Participants took 750 mg of RNE daily at bed-time for two weeks. The study used the Insomnia Severity Index (ISI), the Pittsburgh Sleep Quality Index (PSQI), a sleep diary, the Fatigue Severity Scale (FSS), and the Short Form 36 Health Survey (SF-36) for assessments. Of the 20 participants, 13 completed the study and showed significant improvements in sleep quality. The results showed improvements in ISI and PSQI scores, a 57% reduction in wake-time after sleep onset, and improved sleep efficiency. Although FSS scores remained unchanged, significant improvements were seen in SF-36 physical and mental health scores. The results suggest that RNE is an effective, low-risk option for sleep disturbance, significantly improving sleep quality and overall wellbeing without significant side effects.

Computer-aided design usually gives inspirations and has become a vital strategy to develop novel pesticides through reconstructing natural lead compounds. Patulin, an unsaturated heterocyclic lactone mycotoxin, is a new natural PSII inhibitor and shows significant herbicidal activity to various weeds. However, some evidence, especially the health concern, prevents it from developing as a bioherbicide. In this work, molecular docking and toxicity risk prediction are combined to construct interaction models between the ligand and acceptor, and design and screen novel derivatives. Based on the analysis of a constructed patulin-Arabidopsis D1 protein docking model, in total, 81 derivatives are designed and ranked according to quantitative estimates of drug-likeness (QED) values and free energies. Among the newly designed derivatives, forty-five derivatives with better affinities than patulin are screened to further evaluate their toxicology. Finally, it is indicated that four patulin derivatives, D3, D6, D34, and D67, with higher binding affinity but lower toxicity than patulin have a great potential to develop as new herbicides with improved potency.

Salinity stress poses a significant threat to crop productivity worldwide, necessitating effective mitigation strategies. This study investigated the phytochemical composition and potential of grape seed extract (GSE) to mitigate salinity stress effects on faba bean plants. GC-MS analysis revealed several bioactive components in GSE, predominantly fatty acids. GSE was rich in essential nutrients and possessed a high antioxidant capacity. After 14 days of germination, GSE was applied as a foliar spray at different concentrations (0, 2, 4, 6, and 8 g/L) to mitigate the negative effects of salt stress (150 mM NaCl) on faba bean plants. Foliar application of 2-8 g/L GSE significantly enhanced growth parameters such as shoot length, root length, fresh weight, and dry weight of salt-stressed bean plants compared to the control. The Fv/Fm ratio, indicating photosynthetic activity, also improved with GSE treatment under salinity stress compared to the control. GSE effectively alleviated the oxidative stress induced by salinity, reducing malondialdehyde, hydrogen peroxide, praline, and glycine betaine levels. Total soluble proteins, amino acids, and sugars were enhanced in GSE-treated, salt-stressed plants. GSE treatment under salinity stress modulated the total antioxidant capacity, antioxidant responses, and enzyme activities such as peroxidase, ascorbate peroxidase, and polyphenol oxidase compared to salt-stressed plants. Gene expression analysis revealed GSE (6 g/L) upregulated photosynthesis (chlorophyll a/b-binding protein of LHCII type 1-like (Lhcb1) and ribulose bisphosphate carboxylase large chain-like (RbcL)) and carbohydrate metabolism (cell wall invertase I (CWINV1) genes) while downregulating stress response genes (ornithine aminotransferase (OAT) and ethylene-responsive transcription factor 1 (ERF1)) in salt-stressed bean plants. The study demonstrates GSE\'s usefulness in mitigating salinity stress effects on bean plants by modulating growth, physiology, and gene expression patterns, highlighting its potential as a natural approach to enhance salt tolerance.

The marine environment provides a rich source of distinct creatures containing potentially revolutionary bioactive chemicals. One of these organisms is Caulerpa racemosa, a type of green algae known as green seaweed, seagrapes, or green caviar. This organism stands out because it has great promise for use in medicine, especially in the study of cancer. Through the utilization of computational modeling (in silico) and cellular laboratory experiments (in vitro), the chemical components included in the green seaweed C. racemosa were effectively analyzed, uncovering its capability to treat non-small cell lung cancer (NSCLC). The study specifically emphasized blocking SRC, STAT3, PIK3CA, MAPK1, EGFR, and JAK1 using molecular docking and in vitro. These proteins play a crucial role in the EGFR Tyrosine Kinase Inhibitor Resistance pathway in NSCLC. The chemical Caulersin (C2) included in C. racemosa extract (CRE) has been identified as a potent and effective agent in fighting against non-small cell lung cancer (NSCLC), both in silico and in vitro. CRE and C2 showed a level of inhibition similar to that of osimertinib (positive control/NSCLC drug).

Subjecting the Australian marine-derived fungus Aspergillus noonimiae CMB-M0339 to cultivation profiling using an innovative miniaturized 24-well plate format (MATRIX) enabled access to new examples of the rare class of 2,6-diketopiperazines, noonazines A-C (1-3), along with the known analogue coelomycin (4), as well as a new azaphilone, noonaphilone A (5). Structures were assigned to 1-5 on the basis of a detailed spectroscopic analysis, and in the case of 1-2, an X-ray crystallographic analysis. Plausible biosynthetic pathways are proposed for 1-4, involving oxidative Schiff base coupling/dimerization of a putative Phe precursor. Of note, 2 incorporates a rare meta-Tyr motif, typically only reported in a limited array of Streptomyces metabolites. Similarly, a plausible biosynthetic pathway is proposed for 5, highlighting a single point for stereo-divergence that allows for the biosynthesis of alternate antipodes, for example, the 7R noonaphilone A (5) versus the 7S deflectin 1a (6).

Bleeding resulting from surgical procedures or trauma, including gunshot wounds, represents a life-threatening health issue. Therefore, the development of safe, effective, and convenient hemostatic agents is critical in securing the \"golden time\" to save patients\' lives. Plant-derived compounds and plant extracts have been regarded as promising sources of hemostatic agents in previous studies, regulating hemostatic function with low toxicity and minimal side effects within the human body. Aloe vera-based hydrogels, which are characterized by flexible strength and high functionality, have emerged as a promising platform for wound applications due to their unique biocompatibility features. This study provides a comprehensive exploration of the utilization of thickening agents and natural agents such as xanthan gum, carrageenan, Carbomer, and alginate in applying aloe vera-based hydrogels as a hemostatic. Furthermore, it also tests the use of aloe vera-based hydrogels for therapeutic delivery at wound sites through the incorporation of various antimicrobial agents to extend the utility of the hydrogels beyond hemostasis. Our novel applied research utilizes aloe vera-based hydrogel as an antimicrobial hemostatic agent, providing valuable insights for a wide range of applications and highlighting its potential to enhance hemorrhage control in various emergency scenarios.