Unveiling the Potential of Ent-Kaurane Diterpenoids: Multifaceted Natural Products for Drug Discovery.

Natural products hold immense potential for drug discovery, yet many remain unexplored in vast libraries and databases. In an attempt to fill this gap and meet the growing demand for effective drugs, this study delves into the promising world of ent-kaurane diterpenoids, a class of natural products with huge therapeutic potential. With a dataset of 570 ent-kaurane diterpenoids obtained from the literature, we conducted an in silico analysis, evaluating their physicochemical, pharmacokinetic, and toxicological properties with a focus on their therapeutic implications. Notably, these natural compounds exhibit drug-like properties, aligning closely with those of FDA-approved drugs, indicating a high potential for drug development. The ranges of the physicochemical parameters were as follows: molecular weights-288.47 to 626.82 g/mol; number of heavy atoms-21 to 44; the number of hydrogen bond donors and acceptors-0 to 8 and 1 to 11, respectively; the number of rotatable bonds-0 to 11; fraction Csp3-0.65 to 1; and TPSA-20.23 to 189.53 Ų. Additionally, the majority of these molecules display favorable safety profiles, with only 0.70%, 1.40%, 0.70%, and 46.49% exhibiting mutagenic, tumorigenic, reproduction-enhancing, and irritant properties, respectively. Importantly, ent-kaurane diterpenoids exhibit promising biopharmaceutical properties. Their average lipophilicity is optimal for drug absorption, while over 99% are water-soluble, facilitating delivery. Further, 96.5% and 28.20% of these molecules exhibited intestinal and brain bioavailability, expanding their therapeutic reach. The predicted pharmacological activities of these compounds encompass a diverse range, including anticancer, immunosuppressant, chemoprotective, anti-hepatic, hepatoprotectant, anti-inflammation, antihyperthyroidism, and anti-hepatitis activities. This multi-targeted profile highlights ent-kaurane diterpenoids as highly promising candidates for further drug discovery endeavors.

Unlocking the Potential of Substrate Quality for the Enhanced Antibacterial Activity of Black Soldier Fly against Pathogens.

Globally, antibiotics are facing fierce resistance from multidrug-resistant bacterial strains. There is an urgent need for eco-friendly alternatives. Though insects are important targets for antimicrobial peptides, it has received limited research attention. This study investigated the impact of waste substrates on the production of antibacterial agents in black soldier fly (Hermetia illucens L.) larvae (HIL) and their implications in the suppression of pathogens [Bacillus subtilis (ATCC 6051), Staphylococcus aureus (ATCC 25923), Pseudomonas aeruginosa (ATCC 27853), and Escherichia coli (ATCC 25922)]. The 20% acetic acid (AcOH) extract from market waste had the highest antibacterial activity with an inhibition zone of 17.00 mm, followed by potato waste (15.02 mm) against S. aureus. Hexane extract from HIL raised on market waste also showed a significant inhibitory zone (13.06 mm) against B. subtilis. .Minimum inhibitory concentration (MIC) values recorded were 25 mg/mL against all test pathogens. The fastest time-kill of 20% AcOH extract was 4 h againstB. subtilis, E. coli, ,andP. aeruginosa. Lauric acid was also identified as the dominant component of the various hexane extracts with concentrations of 602.76 and 318.17 µg/g in HIL reared on potato and market waste, respectively. Energy from the market waste substrate correlated significantly (r = 0.97) with antibacterial activities. This study highlights the key role of substrate quality and extraction methods for enhancing the production of antibacterial agents in HIL, thus providing new insights into the development of potential drugs to overcome the alarming concerns of antimicrobial resistance.

Aroma characterization and consumer acceptance of four cookie products enriched with insect (Ruspolia differens) meal.

This research aims to advance knowledge on the impact of four processing methods on volatile compounds from insect-based baked products (cookies) to provide insights on consumer acceptance. Samples were exposed to double step enzyme digestive test, volatiles characterized through headspace analysis, while semi-trained panelists were recruited for the sensory test. Blanched and boiled samples of R. differens had considerably higher digestibility (83.42% and 81.61%, respectively) (p < 0.05) than toasted and deep-fried samples. Insect-based cookie products integrated with blanched and boiled R. differens meal expressed higher digestibility (80.41% and 78.73%, respectively) that was comparable to that of commercial cookie products (control cookies-CTRC with 88.22%). Key volatile compounds common between the various cookie products included, nonanal, octanal, methyl-pyrazine, hexanal, tetradecane, 2-pentylfuran, 2-heptanone, 2E-octenal, 2E-heptenal and dodecane. Among the volatile compounds, pleasant aromas observed were 2E,4E-dodecadienal, pentanal, octanal, methyl pyrazine, furfurals, benzaldehyde, and 2-pentyl furan, which were more pronounced in cookies fortified with boiled, toasted and deep-fried R. differens meal. There was a greater resemblance of sensory characteristics between control cookies and those fortified with deep-fried R. differens. These findings underscore the significant influence of aroma compounds on consumer acceptability and preference for insect-based baked food products, which allows for future process-modification of innate aromas of insect-based meals to produce high-valued pleasant consumer driven market products.

Dynamics in nutrients, sterols and total flavonoid content during processing of the edible Long-Horned grasshopper (Ruspolia differens Serville) for food.

Long-horned grasshopper (Ruspolia differens Serville) is a tasty delicacy in over 20 African countries. This study evaluated the impact of diverse post-harvest thermal treatment (blanching, boiling, toasting, and deep-frying) on the nutrients, total flavonoid content and sterols preservation of R. differens products. Crude protein, ash, and fibre of R. differens was drastically reduced by deep-frying technique. There was increase in Omega-3 (α-linolenic acid), Omega-6 fatty acid (linoleic and arachidonic acids) and sterols [(22Z)-27-Norergosta-5,22-dien-3ß-ol, cholesterol, campesterol, cholest-4-ene-3-one and ß-sitosterol] and flavonoids (2-3 folds) during blanching compared to other techniques. The iron and zinc content increased significantly in blanched and boiled products of R. differens. Thus, losses of nutrients, total flavonoid content and sterols during processing of R. differens for food can be mitigated by employing blanching technique, which is cheaper and least time-consuming. The implications of these dietary and therapeutic compounds on human nutrition and health are discussed.

An Overview of Antimicrobial Compounds from African Edible Insects and Their Associated Microbiota.

The need for easily biodegradable and less toxic chemicals in drug development and pest control continues to fuel the exploration and discovery of new natural molecules. Like certain plants, some insects can also respond rapidly to microbial infections by producing a plethora of immune-induced molecules that include antibacterial and antifungal peptides/polypeptides (AMPs), among other structurally diverse small molecules. The recent recognition that new natural product-derived scaffolds are urgently needed to tackle life-threatening pathogenic infections has been prompted by the health threats posed by multidrug resistance. Although many researchers have concentrated on the discovery of AMPs, surprisingly, edible insect-produced AMPs/small molecules have received little attention. This review will discuss the recent advances in the identification and bioactivity analysis of insect AMPs, with a focus on small molecules associated with the microbiota of selected African edible insects. These molecules could be used as templates for developing next-generation drugs to combat multidrug-resistant pathogens.

Noursamycins, Chlorinated Cyclohexapeptides Identified from Molecular Networking of Streptomyces noursei NTR-SR4.

The noursamycins A-F are chlorinated cyclic hexapeptides, which were identified and isolated from the strain Streptomyces noursei NTR-SR4 overexpressing a LuxR-like transcriptional activator. The molecules were structurally characterized by mass spectrometric analyses and 1D and 2D NMR spectroscopic techniques. The enzymatic machinery involved in the biosynthesis of these peptides is represented by a modular nonribosomal peptide synthetase (NRPS), and the corresponding gene cluster was identified in the S. noursei genome. The latter suggested the biosynthetic pathway for the noursamycins. Spectral networking analysis uncovered noursamycin derivatives that were later found to result from a relaxed substrate specificity of the A3 and A4 adenylation domains of the NRPS. The stereochemistry of the amino acid constituents of the noursamycins was resolved by chemical derivatization, subsequent enantiomer analytics by GC-EIMS, and in silico data analyses. Noursamycins A and B exhibited antibacterial activity against Gram-positive and Gram-negative bacteria, while no apparent cytotoxicity was observed.

Laxitextines A and B, Cyathane Xylosides from the Tropical Fungus Laxitextum incrustatum.

Bioassay-guided fractionation of the mycelial extract of a basidiomycete culture collected in Kenya led to the isolation of two new cyathane diterpenoids named laxitextines A (1) and B (2). The producer strain was characterized by detailed taxonomic studies based on rDNA using the 5.8S gene region, the internal transcribed spacer 2 (ITS2), and part of the large subunit that identified the fungus as Laxitextum incrustatum. The structures of 1 and 2 were elucidated by NMR spectroscopic and mass spectrometric analyses. Both compounds exhibited moderate activities against Gram-positive bacteria Bacillus subtilis (DSM 10), Staphylococcus aureus (DSM 346), and methicillin-resistant Staph. aureus (DSM 1182). The two compounds also showed variable antiproliferative activities against mouse fibroblast (L929) and selected human cell lines (breast cancer MCF-7, epidermoid carcinoma A431, and umbilical vein endothelial HUVEC). The IC50 values with respect to the MCF-7 cell line for compounds 1 and 2 were 2.3 and 2.0 µM, respectively.