The Physicochemical and Functional Properties of Biosurfactants: A Review.

Surfactants, also known as surface-active agents, have emerged as an important class of compounds with a wide range of applications. However, the use of chemical-derived surfactants must be restricted due to their potential adverse impact on the ecosystem and the health of human and other living organisms. In the past few years, there has been a growing inclination towards natural-derived alternatives, particularly microbial surfactants, as substitutes for synthetic or chemical-based counterparts. Microbial biosurfactants are abundantly found in bacterial species, predominantly Bacillus spp. and Pseudomonas spp. The chemical structures of biosurfactants involve the complexation of lipids with carbohydrates (glycolipoproteins and glycolipids), peptides (lipopeptides), and phosphates (phospholipids). Lipopeptides, in particular, have been the subject of extensive research due to their versatile properties, including emulsifying, antimicrobial, anticancer, and anti-inflammatory properties. This review provides an update on research progress in the classification of surfactants. Furthermore, it explores various bacterial biosurfactants and their functionalities, along with their advantages over synthetic surfactants. Finally, the potential applications of these biosurfactants in many industries and insights into future research directions are discussed.

Production, characterization, and potential applications of lipopeptides in food systems: A comprehensive review.

Lipopeptides are a class of lipid-peptide-conjugated compounds with differing structural features. This structural diversity is responsible for their diverse range of biological properties, including antimicrobial, antioxidant, and anti-inflammatory activities. Lipopeptides have been attracting the attention of food scientists due to their potential as food additives and preservatives. This review provides a comprehensive overview of lipopeptides, their production, structural characteristics, and functional properties. First, the classes, chemical features, structure-activity relationships, and sources of lipopeptides are summarized. Then, the gene expression and biosynthesis of lipopeptides in microbial cell factories and strategies to optimize lipopeptide production are discussed. In addition, the main methods of purification and characterization of lipopeptides have been described. Finally, some biological activities of the lipopeptides, especially those relevant to food systems along with their mechanism of action, are critically examined.

A decade's overview of 2-aminothiophenes and their fused analogs as promising anticancer agents.

Over the past decades, cancer has been a challenging domain for medicinal chemists as it is an international health concern. In association, small molecules such as 2-aminothiophenes and their derivatives showed significant antitumor activity through variable modes of action. Therefore, this article aims to review the advances regarding these core scaffolds over the past 10 years, where 2-aminothiophenes and their fused analogs are classified and discussed according to their biological activity and mode of action, in the interest of boosting new design pathways for medicinal chemists to develop targeted antitumor candidates.

Effect of consumption of sheep and cow milk on rat brain fatty acid and phospholipid composition.

The effect of sheep milk and cow milk on the lipid composition of rat brain was investigated in two feeding experiments of 28-days duration. Total lipids of the rat brain were extracted using ethanol-hexane, and the fatty acids and phospholipid contents analysed using gas chromatography with flame ionization detection (GC-FID) and phosphorus-31 nuclear magnetic resonance (31P NMR). Furthermore, freeze-dried pooled samples were analysed using attenuated total reflectance Fourier Transform Infrared and Fourier Transform Raman Spectroscopy and analysed with multivariate methods. A significantly (P < 0.05) higher C18:2 content was found in the cow milk group compared with sheep milk-treated groups in Study one. In Study two, a significantly (P < 0.05) lower C16:0 content was present in the sheep milk-treated group compared to the control low Ca/P group. No significant (P > 0.05) differences were observed in the spectroscopy analyses. It is concluded that sheep and cow milks fed to rats for 28-days had a low effect on the brain lipidome.

Ciprofloxacin Derivative-Loaded Nanoparticles Synergize with Paclitaxel Against Type II Human Endometrial Cancer.

Combinations of chemotherapeutic agents comprise a clinically feasible approach to combat cancers that possess resistance to treatment. Type II endometrial cancer is typically associated with poor outcomes and the emergence of chemoresistance. To overcome this challenge, a combination therapy is developed comprising a novel ciprofloxacin derivative-loaded PEGylated polymeric nanoparticles (CIP2b-NPs) and paclitaxel (PTX) against human type-II endometrial cancer (Hec50co with loss of function p53). Cytotoxicity studies reveal strong synergy between CIP2b and PTX against Hec50co, and this is associated with a significant reduction in the IC50 of PTX and increased G2/M arrest. Upon formulation of CIP2b into PEGylated polymeric nanoparticles, tumor accumulation of CIP2b is significantly improved compared to its soluble counterpart; thus, enhancing the overall antitumor activity of CIP2b when co-administered with PTX. In addition, the co-delivery of CIP2b-NPs with paclitaxel results in a significant reduction in tumor progression. Histological examination of vital organs and blood chemistry was normal, confirming the absence of any apparent off-target toxicity. Thus, in a mouse model of human endometrial cancer, the combination of CIP2b-NPs and PTX exhibits superior therapeutic activity in targeting human type-II endometrial cancer.

Edible packaging systems for enhancing the sensory quality of animal-derived foods.

Maintaining the sensory quality of animal-derived foods from paddock to plate is a big challenge due to their fatty acid profile and susceptibility to oxidative changes and microbial spoilage. Preventive measures are taken by manufacturers and retailers to offset the adverse effects of storage to present animal foods to consumers with their best sensory attributes. The use of edible packaging systems is one of the emerging strategies that has recently attracted the attention of researchers and food processors. However, a review that specifically covers the edible packaging systems focused on improving the sensory quality of animal-derived foods is missing in the literature. Therefore, the objective of this review is to discuss in detail various edible packaging systems currently available and their mechanisms for enhancing the sensory properties of animal-derived foods. The review includes the findings of recent papers published during the last 5 years and summarises the novel materials and bioactive agents.

Modulating leishmanial pteridine metabolism machinery via some new coumarin-1,2,3-triazoles: Design, synthesis and computational studies.

In accordance with WHO statistics, leishmaniasis is one of the top neglected tropical diseases, affecting around 700 000 to one million people per year. To that end, a new series of coumarin-1,2,3-triazole hybrid compounds was designed and synthesized. All new compounds exerted higher activity than miltefosine against L. major promastigotes and amastigotes. Seven compounds showed single digit micromolar IC50 values whereas three compounds (13c, 14b and 14c) displayed submicromolar potencies. A mechanistic study to elucidate the antifolate-dependent activity of these compounds revealed that folic and folinic acids abrogated their antileishmanial effects. These compounds exhibited high safety margins in normal VERO cells, expressed as high selectivity indices. Docking simulation studies on the folate pathway enzymes pteridine reductase and DHFR-TS imparted strong theoretical support to the observed biological activities. Besides, docking experiments on human DHFR revealed minimal binding interactions thereby highlighting the selectivity of these compounds. Predicted in silico physicochemical and pharmacokinetic parameters were adequate. In view of this, the structural characteristics of these compounds demonstrated their suitability as antileishmanial lead compounds.

Studies on the Effect of Oxidation on Bioactivity of Phenolics and Wine Lees Extracts.

It is expected that any processing and handling of lees (e.g., drying, storage or removal of residual alcohol using various concentration techniques) will expose the material to oxidation and the consequences of oxidation on the biological activity of the lees and the lees extracts are unknown. The effects of oxidation (using horseradish peroxidase and hydrogen peroxide model system) on phenolic composition and their antioxidant and antimicrobial activities were investigated in (i) a flavonoid model system composed of catechin and grape seed tannin (Cat:GST) extracts at various ratios and (ii) in Pinot noir (PN) and Riesling (RL) wine lees samples. For the flavonoid model, oxidation had a minor or no impact on total phenol content but increased (p < 0.05) total tannin content from approximately 145 to 1200 µg epicatechin equivalent/mL. An opposite observation was found in the PN lees samples where oxidation reduced (p < 0.05) the total phenol content (TPC) by approximately 10 mg GAE/g dry matter (DM) lees. The mean degree of the polymerization (mDP) values of the oxidized flavonoid model samples ranged from 15 to 30. The Cat:GST ratio and interaction of the Cat:GST ratio with oxidation were found significantly to affect the mDP values of the flavonoid model samples (p < 0.05). Oxidation increased the mDP values in all oxidized flavonoid model samples except for Cat:GST 0:100. The mDP values of the PN lees samples ranged from 7 to 11 and remained the same after oxidation. There was no significant reduction in the antioxidant activities (DPPH and ORAC) of the model and wine lees after oxidation except the PN1 lees sample (decreased from 3.5 to 2.8 mg Trolox equivalent/g DM extracts). In addition, no correlation was observed between mDP (approximately 10 to 30) and DPPH (0.09) and ORAC assay (-0.22), which indicates that the higher mDP resulted in a poor ability to scavenge DPPH· and AAPH· free radicals. Antimicrobial activities of the flavonoid model were found to be improved after the oxidation treatment against S. aureus and E. coli with minimum inhibition concentration (MIC) of 1.56 and 0.39 mg/mL. This may indicate that new compounds were formed during the oxidation treatment, and these compounds showed more effective microbicidal activity. LC-MS work is required in the future to identify the compounds that are newly formed during the oxidation of the lees.

Marine Fish-Derived Lysophosphatidylcholine: Properties, Extraction, Quantification, and Brain Health Application.

Long-chain omega-3 fatty acids esterified in lysophosphatidylcholine (LPC-omega-3) are the most bioavailable omega-3 fatty acid form and are considered important for brain health. Lysophosphatidylcholine is a hydrolyzed phospholipid that is generated from the action of either phospholipase PLA1 or PLA2. There are two types of LPC; 1-LPC (where the omega-3 fatty acid at the sn-2 position is acylated) and 2-LPC (where the omega-3 fatty acid at the sn-1 position is acylated). The 2-LPC type is more highly bioavailable to the brain than the 1-LPC type. Given the biological and health aspects of LPC types, it is important to understand the structure, properties, extraction, quantification, functional role, and effect of the processing of LPC. This review examines various aspects involved in the extraction, characterization, and quantification of LPC. Further, the effects of processing methods on LPC and the potential biological roles of LPC in health and wellbeing are discussed. DHA-rich-LysoPLs, including LPC, can be enzymatically produced using lipases and phospholipases from wide microbial strains, and the highest yields were obtained by Lipozyme RM-IM®, Lipozyme TL-IM®, and Novozym 435®. Terrestrial-based phospholipids generally contain lower levels of long-chain omega-3 PUFAs, and therefore, they are considered less effective in providing the same health benefits as marine-based LPC. Processing (e.g., thermal, fermentation, and freezing) reduces the PL in fish. LPC containing omega-3 PUFA, mainly DHA (C22:6 omega-3) and eicosapentaenoic acid EPA (C20:5 omega-3) play important role in brain development and neuronal cell growth. Additionally, they have been implicated in supporting treatment programs for depression and Alzheimer's. These activities appear to be facilitated by the acute function of a major facilitator superfamily domain-containing protein 2 (Mfsd2a), expressed in BBB endothelium, as a chief transporter for LPC-DHA uptake to the brain. LPC-based delivery systems also provide the opportunity to improve the properties of some bioactive compounds during storage and absorption. Overall, LPCs have great potential for improving brain health, but their safety and potentially negative effects should also be taken into consideration.

A ciprofloxacin derivative with four mechanisms of action overcomes paclitaxel resistance in p53-mutant and MDR1 gene-expressing type II human endometrial cancer.

Dysfunction of the p53 gene and the presence of the MDR1 gene are associated with many malignant tumors including endometrial cancer and are responsible for cancer therapeutic resistance and poor survival. Thus, there is a critical need to devise novel combinatorial therapies with multiple mechanisms of action to overcome drug resistance. Here, we report a new ciprofloxacin derivative (CIP2b) tested either alone or in combination with taxanes against four human endometrial cancer cell lines. In vitro studies revealed that a combination of paclitaxel + CIP2b had synergistic cytotoxic effects against MDR1-expressing type-II human endometrial cancer cells with loss-of-function p53 (Hec50co LOFp53). Enhanced antitumor effects were confirmed by substantial increases in caspase-3 expression, cell population shifts toward the G2/M phase, and reduction of cdc2 phosphorylation. It was found that CIP2b targets multiple pathways including the inhibition of MDR1, topoisomerase I, and topoisomerase II, as well as enhancing the effects of paclitaxel (PTX) on microtubule assembly. In vivo treatment with the combination of PTX + CIP2b also led to significantly increased accumulation of PTX in tumors (compared to CIP2b alone) and reduction in tumor growth. Enhanced in vivo cytotoxic effects were confirmed by histological and immunohistochemical examination of the tumor tissues. Complete blood count and blood biochemistry data confirmed the absence of any apparent off-target toxicity. Thus, combination therapy involving PTX and CIP2b targeted multiple pathways and represents an approach that could result in improved tolerance and efficacy in patients with type-II endometrial cancer harboring the MDR1 gene and p53 mutations.

Design, synthesis, cytotoxic activities, and molecular docking of chalcone hybrids bearing 8-hydroxyquinoline moiety with dual tubulin/EGFR kinase inhibition.

The present study established thirteen novel 8-hydroxyquinoline/chalcone hybrids3a-mof hopeful anticancer activity. According to NCI screening and MTT assay results, compounds3d-3f, 3i,3k,and3ldisplayed potent growth inhibition on HCT116 and MCF7 cells compared to Staurosporine. Among these compounds,3eand3fshowed outstanding superior activity against HCT116 and MCF7 cells and better safety toward normal WI-38 cells than Staurosporine. The enzymatic assay revealed that3e,3d, and3ihad goodtubulin polymerization inhibition (IC50 = 5.3, 8.6, and 8.05 µM, respectively) compared to the reference Combretastatin A4 (IC50 = 2.15 µM). Moreover,3e,3l, and3fexhibited EGFR inhibition (IC50 = 0.097, 0.154, and 0.334 µM, respectively) compared to Erlotinib (IC50 = 0.056 µM). Compounds3eand3fwere investigated for their effects on the cell cycle, apoptosis induction, andwnt1/ß-cateningene suppression. The apoptosis markers Bax, Bcl2, Casp3, Casp9, PARP1, and ß-actin were detected by Western blot. In-silico molecular docking, physicochemical, and pharmacokinetic studies were implemented for the validation of dual mechanisms and other bioavailability standards. Hence, Compounds3eand3fare promising antiproliferative leads with tubulin polymerization and EGFR kinase inhibition.

In Vitro Anticancer Activity of Novel Ciprofloxacin Mannich Base in Lung Adenocarcinoma and High-Grade Serous Ovarian Cancer Cell Lines via Attenuating MAPK Signaling Pathway.

Novel drugs are desperately needed in order to combat a significant challenge due to chemo-therapeutic resistance and bad prognosis. This research aimed to assess the anticancer activity of a newly synthesized ciprofloxacin Mannich base (CMB) on ovarian cancer (OVCAR-3) and lung cancer (A-549) cell lines and to investigate probable involved molecular mechanisms. The cytotoxic and pro-apoptotic impact of CMB on both cell lines was investigated using MTT assay, Annexin V assay, and cell cycle analysis, as well as caspase-3 activation. Western blotting was carried out to evaluate downstream targets of the MAPK pathway, while qRT PCR was used to evaluate the gene expression pattern of the p53/Bax/Bcl2 pathway. CMB treatment showed significantly reduced cell proliferation in both OVCAR-3 and A-549 cells with half maximum inhibitory concentration (IC50) = 11.60 and 16.22 µg/mL, respectively. CMB also induced apoptosis, S phase cell cycle arrest, and up-regulated expression of p53, p21, and Bax while down-regulated Bcl2 expression. CMB also halted cell proliferation by deactivating the MAPK pathway. In conclusion, CMB may be regarded as a potential antiproliferative agent for lung and ovarian cancers due to anti-proliferative and pro-apoptotic actions via inhibition of the MAPK pathway and p53/Bax/Bcl2.

Positional Distribution of Fatty Acids in Processed Chinook Salmon Roe Lipids Determined by 13C Magnetic Resonance Spectroscopy (NMR).

Recently, there has been great interest in the lipidomic of marine lipids and their potential health benefits. Processing of seafood products can potentially modify the characteristics and composition of lipids. The present study investigated the effect of processing methods (salting and fermentation) on the positional distribution of fatty acids of Chinook salmon roe using 13C nuclear magnetic resonance spectroscopy (NMR). The NMR analysis provided information on the carbonyl atom, double bond/olefinic, glycerol backbone, aliphatic group, and chain ending methyl group regions. The obtained data showed that docosahexaenoic acid (DHA) is the main fatty acid esterified at the sn-2 position of the triacylglycerides (TAGs), while other fatty acids, such as eicosapentaenoic acid (EPA) and stearidonic acid (SDA), were randomly distributed or preferentially esterified at the sn-1 and sn-3 positions. Fermentation of salmon roe was found to enrich the level of DHA at the sn-2 position of the TAG. The processing of roe by both salt drying and fermentation did not appear to affect the proportion of EPA at the sn-2 position. This present study demonstrated that fish roe processing can enhance the proportion of DHA at the sn-2 position and potentially improve its bioavailability.

Integration of LC/MS, NMR and Molecular Docking for Profiling of Bioactive Diterpenes from Euphorbia mauritanica L. with in Vitro Anti-SARS-CoV-2 Activity.

In spite of tremendous efforts exerted in the management of COVID-19, the absence of specific treatments and the prevalence of delayed and long-term complications termed post-COVID syndrome still urged all concerned researchers to develop a potent inhibitor of SARS-Cov-2. The hydromethanolic extracts of different parts of E. mauritanica were in vitro screened for anti-SARS-Cov-2 activity. Then, using an integrated strategy of LC/MS/MS, molecular networking and NMR, the chemical profile of the active extract was determined. To determine the optimum target for these compounds, docking experiments of the active extract's identified compounds were conducted at several viral targets. The leaves extract showed the best inhibitory effect with IC50 8.231±0.04 µg/ml. The jatrophane diterpenes were provisionally annotated as the primary metabolites of the bioactive leaves extract based on multiplex of LC/MS/MS, molecular network, and NMR. In silico studies revealed the potentiality of the compounds in the most active extract to 3CLpro, where compound 20 showed the best binding affinity. Further attention should be paid to the isolation of various jatrophane diterpenes from Euphorbia and evaluating their effects on SARS-Cov-2 and its molecular targets.

Aloe barbadensis Based Bioactive Edible Film Improved Lipid Stability and Microbial Quality of the Cheese.

An attempt was made to develop a bioactive edible film using carrageenan and A. vera gel for enhancing the storage quality of cheese using kalari, a popular Himalayan cheese, as a food-model system. The film was evaluated for various physicomechanical and oxidative properties (ABTS (2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonate)) and DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activities, total flavonoid and phenolic contents). Based on preliminary trials, 1% A. vera gel was found to be optimum. The addition of the gel resulted in a significant decrease in moisture content, transparency, solubility, and water-vapor transmission rate and increased the thickness and density of the film. The film showed antimicrobial properties against E. coli and significantly (p < 0.05) decreased the lipid-oxidation (thiobarbituric acid reactive substances, free-fatty acids, and peroxide values) and increased microbial-quality (total-plate, psychrophilic, and yeast/molds) of the samples during 4-week refrigerated storage (4 ± 1 °C). The film also exhibited a significant positive impact on the sensory quality of the cheese, indicating the potential for commercial applications for quality control of cheese during storage.

Synthesis and molecular docking of new N4-piperazinyl ciprofloxacin hybrids as antimicrobial DNA gyrase inhibitors.

A series of N-4 piperazinyl ciprofloxacin derivatives as urea-tethered ciprofloxacin-chalcone hybrids 2a-j and thioacetyl-linked ciprofloxacin-pyrimidine hybrids 5a-i were synthesized. The target compounds were investigated for their antibacterial activity against S. aureus, P. aeruginosa, E. coli, and C. albicans strains, respectively. Ciprofloxacin derivatives 2a-j and 5a-i revealed broad antibacterial activity against either Gram positive or Gram negative strains, with MIC range of 0.06-42.23 µg/mL compared to ciprofloxacin with an MIC range of 0.15-3.25 µg/mL. Among the tested compounds, hybrids 2b, 2c, 5a, 5b, 5h, and 5i exhibited remarkable antibacterial activity with MIC range of 0.06-1.53 µg/mL against the tested bacterial strains. On the other hand, compounds 2c, 2e, 5c, and 5e showed comparable antifungal activity to ketoconazole against candida albicans with MIC range of 2.03-3.89 µg/mL and 2.6 µg/mL, respectively. Further investigations showed that some ciprofloxacin hybrids have inhibitory activity against DNA gyrase as potential molecular target compared to ciprofloxacin with IC50 range of 0.231 ± 0.01-7.592 ± 0.40 µM and 0.323 ± 0.02 µM, respectively. Docking studies of compounds 2b, 2c, 5b, 5c, 5e, 5h, and 5i on the active site of DNA gyrase (PDB: 2XCT) confirmed their ability to form stable complex with the target enzyme like that of ciprofloxacin.

Characterization of Bioactive Compounds in Lees from New Zealand Wines with Different Vinification Backgrounds.

Wine lees are one of the main by-products produced during winemaking. Little is known about the effect of the vinification technique on the phenolic compounds and the biological activity of wine lees extracts. Wine lees collected at varying vinification sources of two grape varieties, Riesling (RL) and Pinot Noir (PN), were analyzed for total phenolic content (TPC), tannin content (TTC), their anthocyanin and phenolic profile, and the antioxidant and antimicrobial activities of their extracts. The results showed a low TPC and TTC in RL lees, which could be attributed to the varietal characteristic of RL grapes and to less skin contact during vinification. Vinification techniques modified the composition of the phenolic compounds in the lees. The results showed a good linear relationship between the antioxidant activities and the TPC and TTC, indicating that PN lees were better sources of phenolics and antioxidant activity than RL lees. The antimicrobial activity of wine lees was related to the phenolic composition rather than the quantity of total phenolics. Knowing the grape and wine processing conditions can provide some insights into the potential composition of wine lees and, hence, determine the potential economic use of the by-product.

Development and validation of molnupiravir assessment in bulk powder and pharmaceutical formulation by the RP-HPLC-UV method.

An accurate, sensitive and selective RP-HPLC-UV method has been established for the estimation of Molnupiravir (MOL) in pure bulk powder and pharmaceutical formulation. Separation was achieved on an Inertsil C18 column (150.0 mm × 4.6 mm, 5.0 µm), using a mobile phase of 20 mM phosphate buffer pH 2.5 : acetonitrile (80 : 20, v/v%) in isocratic mode with a flow rate of 1.0 mL min-1. The λ max of MOL prepared in the chosen diluent (ethanol : water in equal proportions) was found to be 230.0 nm. The constructed calibration curve was found to be linear in the concentration range of 0.2-80.0 µg mL-1. The recovery% of MOL using the proposed method was 100.29%. The limit of detection (LOD) and limit of quantification (LOQ) were 0.04 µg mL-1 and 0.12 µg mL-1, respectively. No significant interference was detected in the presence of the common pharmaceutical formulation excipients. The method was validated following the ICH recommendations. All the obtained results were statistically compared with those using reported methods and there were no significant differences. The method developed in this work was successfully employed for the assessment of MOL in bulk powder and pharmaceutical formulation.

New potent ciprofloxacin-uracil conjugates as DNA gyrase and topoisomerase IV inhibitors against methicillin-resistant Staphylococcus aureus.

A series of ciprofloxacin-uracil conjugates 5a-t were synthesized and identified by 1H NMR, 13C NMR, mass spectroscopy and elemental analyses. The antibacterial results revealed that the new derivatives exhibited better activity against Gram-positive than the Gram-negative strains; most of the target compounds exhibited good activities against S. aureus ATCC 6538. Compounds 5b and 5g possess the highest activities with MICs of 1.25 and 2.37 µM, respectively, which are more potent than the parent drug ciprofloxacin, MIC, 7.58 µM. In addition, they also exhibited potent activities against MRSA AUMC 261 with MICs, 0.031 and 0.046 µM respectively, higher than ciprofloxacin with MIC, 0.57 µM. Moreover, compounds 5b and 5g showed potent inhibitory activities against DNA gyrase (IC50 = 1.72 and 5.72 µM) and topoisomerase IV (4.36 and 7.77 µM) compared to ciprofloxacin with IC50 values 0.66 and 8.16 µM, respectively. The molecular docking study revealed that compounds 5b and 5g may formed stable interaction with the active sites of DNA gyrase and topoisomerase IV similar to ciprofloxacin. Hence, 5b and 5g are considered promising antibacterial candidated against MRSA AUMC 261 strains that requires further optimization.