Annona squamosa has been traditionally used and has demonstrated promising therapeutic properties. However, there remains a lack of comprehensive comparative evaluation of the phytochemical composition and biological activities among its different fruit parts. The present work aimed to examine the chemical compositions of seed (MSS), pulp and peels (JSW) and assess antioxidant, anti-inflammatory, and anticancer activities of the Annona squamosa fruits procured from the Iraqi market. The antioxidant capacity using DPPH, ABTS, 5-LOX, and ORAC assays and the anti-inflammatory COX1/COX2 inhibition assays were determined. In addition, anticancer potential against HepG2 (liver), MCF-7 (breast), and Colo-205 (colon) cell lines were investigated via MTT- assay, flow cytometry for cell cycle distribution, and apoptosis analysis. Phytochemical profiling was also conducted using LC-HRESIMS. Among the extracts, MSS exhibited the strongest antioxidant activity. JSW on the other hand demonstrated higher activity in DPPH and ABTS assays. Furthermore, MSS displayed significant cytotoxic effects against cancer cells. Overall, the findings underscore the pharmacological potential of A. squamosa seeds and fruits (pulp and peels) extracts, particularly MSS, as valuable sources of antioxidant, anti-inflammatory, and anticancer agents. This study highlights the promise of A. squamosa as a sustainable candidate for drug development and nutraceutical applications, while also emphasizing the health benefits of fruit waste utilization.

Staphylococcus aureus infections, particularly methicillin-resistant strains, pose major diagnostic challenges in differentiating septic from aseptic inflammation. This study aimed to radiolabel diosmetin (3',5,7-trihydroxy-4'-methoxyflavone), a natural flavonoid with antibacterial and anti-inflammatory properties, with iodine-131 (131I) and to evaluate its potential as a radiotracer for infection imaging. Diosmetin was isolated from Rosmarinus officinalis and radiolabeled with Na131I using the chloramine-T method. The radiochemical yield (RCY), and stability were assessed using TLC/HPLC. Molecular docking to COX-2 (PDB: 5KIR) was performed using the MOE software. In vitro binding to S. aureus was measured, and biodistribution studies were conducted in normal, inflamed, and infected Swiss Albino mice (n = 7 per subgroup) at 0.5-3 h post-injection. Target-to-non-target (T/NT) ratios were calculated from the %ID/g values. Radiolabeling achieved 95.8 ± 0.12% yield with >3 h of stability in PBS and serum. Docking revealed a strong COX-2 affinity. In vitro binding to S. aureus reached 52 ± 1.5%. In infected mice, [131I]DSM accumulated selectively in the infected muscle (3.85 ± 0.10%ID/g at 2 h), yielding a T/NT ratio of 7.7, which was double that in inflamed tissue (3.7). Rapid blood clearance, predominant renal excretion, and low thyroid uptake confirmed the in vivo stability. [131I]Diosmetin was prepared with high yield and stability, demonstrated selective uptake at infectious foci, and enabled clear differentiation between septic and aseptic inflammation. These findings support its potential as a promising radiotracer for infection imaging applications.

A plethora of studies have been explored to identify effective, safe, and economical alternatives to potentially hazardous antibiotics. Natural extracts of marine organisms and their secondary metabolites are among the intriguing study topics to address this growing concern. This study aimed to investigate the effects of ten purified metabolites isolated from the isolated marine-derived bacterial strain, Enterobacter cloacae GH1 on various resistant pathogens. E. cloacae GH1 was isolated from Red Sea alga, Cystoseira myrica, together with other strains and has been chosen as a promising isolate based on its high microbial inhibition zones towards tested Gram-positive and-negative bacteria. Moreover, metabolomic analysis using (LC-HRESIMS) was conducted for different fractions of ethyl-acetate extract of E. cloacae GH1 for de-replication of biosynthesized and/or produced metabolites. Most de-replicated metabolites were isolated and purified using advanced preparative techniques followed by subsequent antimicrobial and docking studies. Results indicated that ethyl-acetate extract of E. cloacae GH1 significantly increased microbial growth inhibition, especially Staphylococcus aureus and Sarcina maxima. Moreover, metabolomic profiling showed the presence of diverse phytochemicals, mostly diketopiprazines. In addition, purification of the extract afforded 8 diketopiperazine derivatives, namely cyclo(S-Pro-S-Tyr) (E1), cyclo(S-Pro-S-Val) (E2), Brevianamide F (E3), cyclo(S-hyp-S-Pro-S-Phe) (E4), cyclo(R-hy-S-Pro-R-Phe) (E5), cyclo(S-hy-S-Pro-S-Lue) (E6), cyclo(S-hy-R-Pro-S-Lue) (E7), and cyclo(S-Pro-Gly) (E8) together with 2 indole derivatives, indole-3-aldehyde (E9) and indole-3-acetic acid (E10). In accordance with those purified metabolites, only indole derivatives demonstrated remarkable bioactivity against tested microbes. A docking study on two different virulence proteins showed that E9 and E10 actively bind and interact with virulence proteins, assuring their ability to decrease microbial growth. In conclusion, the identified indole derivatives exhibited promising anti-biofilm and anti-virulence properties, suggesting potential for antibiotic development.

Tamarix sp., often known as tamarisk, is a wide genus of flowering plants that reduce inflammation and cure wounds. In addition, using honey for wound therapy and care dates back thousands of years. Herein, we aimed to assess the wound healing potential of Saudi Tamarix honey (STH) metabolites in vivo, and support our hypothesis through in silico studies. Using an excision wound model, the possibility of Tamarix honey for in vivo wound healing was investigated via examining its effects on molecular targets involved in wound healing, including TGF-β, VEGF, matrix metalloproteinase-1 (MMP-1), TNF-α, and IL-1β. In addition, physicochemical properties were examined, and 1H NMR based metabolomics technique was employed to identify STH chemical metabolites. Results revealed that Tamarix honey had a substantial impact on wound closure rate, increased levels of TGF-β and VEGF, and markedly decreased the gene expression of MMP-1, TNF-α, and IL-1β compared to the group treated with topical MEBO ointment. Biochemical and histological studies corroborated the phenotypic results. Furthermore, the effect of Tamarix honey on the redox state of wounds was investigated. On the other hand, the physical and chemical properties of STH demonstrated that it possesses moisture content 14.60%, glucose 33.7%, fructose 37.9%, sucrose 5.0%, pH 5.0, hydroxymethylfurfural (HMF) 15.40 mg/kg, and diastase enzyme 17.6 Goth scale Min, all of which that attest to its superior quality and compliance with both national and international requirements. 1H NMR based metabolomics analysis revealed thirteen metabolites, mainly flavonoids. All Tamarix honey-derived flavonoids demonstrated high target probability against two wound healing-related targets, namely, glycogen synthase kinase-3β (GSK-3β) and NADPH oxidase 4 (NOX4). Alternatively, Tamarix honey-derived chlorogenic acid showed a high probability of targeting MMP-2, which was verified by molecular docking and molecular dynamics simulation (MDS). Our study highlights the potential of Tamarix honey in wound repair by revealing the most likely signaling pathway utilizing in silico and gene expression analysis.

The emergence of multidrug-resistant bacterial infections is a major global public health concern. Human health is in danger from microorganisms that have developed resistance to currently used drugs. Honey is well known for its significant activity against antibiotic-resistant bacteria. In this study, the antibacterial properties of honey from various botanical sources in Saudi Arabia against seven significant nosocomial and foodborne pathogens were investigated. The physicochemical properties of four Saudi honey samples—aloe honey (HO1) (Aloe vera L.), anise honey (HO2) (Pimpinella anisum L.), moringa honey (HO4) (Moringa oleifera Lam.), and acacia honey (HO5) (Acacia sp.)—were examined. In addition, they were screened for antibacterial activity against ESKAPE pathogens (Enterobacter faecalis, Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Salmonella Typhimurium, Escherichia coli, and Enterobacter sp.) and anti-biofilm activity against four pathogenic bacteria strains: S. aureus, P. aeruginosa, S. typhimurium, and E. coli. 1H NMR profiling and multivariate analysis (PCA and PLS-DA) were performed. Aloe honey (HO1) was the most distinct sample based on MVDA and its antibacterial activity, and it exhibited anti-biofilm activity against most biofilm-forming microorganisms. Its metabolic profile was deduced using LC-MS, and the resulting annotated compounds were docked against several β-lactamase enzyme classes. The results reveal the potential of honey-derived compounds to inhibit β-lactamases due to the presence of gallic acid hexoside and rosmarinic acid, suggesting their potential as competitive inhibitors. Our findings suggest that further honey antibacterial compounds could offer a novel approach to overcoming antibiotic resistance by targeting and inhibiting β-lactamase enzymes.

OBJECTIVE:This study aims to assess the antibacterial potential of kojic acid produced by Trichoderma harzianum, a fungus isolated from the River Nile, and its potential application as a natural food preservative against Listeria monocytogenes. METHODS:A comprehensive chemical analysis of the ethyl acetate extract of T. harzianum was conducted using chromatographic and spectroscopic techniques. The isolated compounds were subsequently evaluated for their antibacterial activity and cytotoxic effects. RESULTS:Three major secondary metabolites were identified and purified from T. harzianum: kojic acid, di-(2-ethylhexyl) phthalate, and phomaligol A. Among these, only kojic acid demonstrated moderate antibacterial activity against L. monocytogenes, with negligible cytotoxicity against liver and colorectal cancer cell lines (IC50: 41.34 ± 1.7 μM and 17.35 ± 0.8 μM, respectively). In situ studies revealed a dose-dependent antibacterial effect of kojic acid against L. monocytogenes in skimmed milk. Further evaluation across different dairy products indicated that its efficacy was influenced by fat content, leading to a bacterial count reduction of up to 4.17 log units. Additionally, kojic acid effectively inhibited bacterial growth under both low and high contamination levels. Notably, it preserved milk stored at room temperature by preventing bacterial overgrowth for up to four days. CONCLUSION:These findings suggest that kojic acid possesses significant potential as a natural milk preservative due to its selective antibacterial activity against L. monocytogenes and favorable safety profile. As a result, kojic acid could serve as a viable alternative to synthetic chemical preservatives in dairy products.

Currently, diabetes mellitus (DM) is regarded as one of the leading ten key factors contributing to mortality on a global scale. The rate of its occurrence has risen to the epidemic levels. Pioglitazone; PPAR-gamma agonist, is commonly used oral hypoglycemic drugs. In this study, a newly antidiabetic component has been synthesized and fully characterized; after that, its pharmacokinetic parameters have been determined after analysis using the HPLC method, which is important to determine its effect in the body as well as its time course. After that, the measured parameters were compared to the pharmacokinetic parameters of the widely used antidiabetic; pioglitazone. A novel and convenient HPLC approach was introduced to analyze the synthesized component in its pure form and in rat plasma samples after removing plasma protein using methanol. The method depended on using C18 column and a mobile phase of methanol: water (30: 70, v/v), running rate of 1.5 mL/min with UV recognition at 280 nm. Linearity was proved in the range of 0.3-50.0 mu g/mL, and US Food and Drug Administration (FDA) guidelines were followed during method validation, all findings ensured the validity of the method. The work was extended to study the pharmacokinetics of the new component and then compared to those of pioglitazone. The outcomes showed that the new component has shorter Tmax than pioglitazone (0.5 h comparing to 3.5 h for pioglitazone) with nearly the same maximum plasma concentration. Additionally, it has higher distribution and clearance rate volume than pioglitazone. Finally, four novel green metrics, including the Analytical Eco-scale, Analytical GREEnness Calculator (AGREE), complex modified GAPI (ComplexMoGAPI), and AGREE-prep were applied to estimate the environmental impact of the methods of analysis, synthesis, and sample preparation. All findings proved the little environmental impact of the newly developed approach.

Gold nanoparticles (Au) have attracted considerable attention in the field of biomedicine in recent years.

BackgroundHoney's medical values have been extensively recorded in literature. Yemeni Sidr honey was reported to treat many ailments like stomach and respiratory disorders. ESKAPE and other multidrug-resistant pathogens are considered one of the top three risks to global public health, so alternative strategies become critical demand against such pathogens or their biofilms. The current study aimed to explore the antibacterial and antioxidant potential of the Yemeni Sidr honey extracts. The antibacterial activity of the two Yemeni Sidr honey extracts (ST and SM) was assessed against different pathogenic strains. The antioxidant activity was also evaluated using ORAC, ABST, 5-LOX, and DPPH. Furthermore, 2D HSQC data of both ST and SM honey extracts were collected uploaded to the SMART platform to identify the possible metabolites in these extracts. The identified metabolites were analyzed using docking and molecular dynamic simulations (MDS) to identify the key players in the antibacterial action.ResultsThe antibacterial activity revealed that ST and SM extracts have similar activity against all tested pathogens. ST extract exhibited superior antibiofilm effect against P. aeruginosa and C. albicans by 68.2% and 62.6%, respectively, exceeding the reference standards. Moreover, ST extract displayed the highest antioxidant power against all assays except the DPPH assay. SMART dereplication of the HSQC data of ST extract revealed the annotations of five carbohydrates (fructose, glucose, mannose, maltose, and sucrose); while, SM extract showed three major phenolic compounds (chrysin, ellagic acid, and caffeic acid), in which chrysin and ellagic acid were likely the key players in the antibacterial action, based on MDS.ConclusionsThe study confirmed the effectiveness of Sidr honey against the tested multidrug-resistant pathogens. Additionally, our observations shed the light on the main secondary constituents in Yemini Sidr honey extracts, and their effective role in multidrug-resistant pathogens growth inhibition.

Pseudomonas aeruginosa (PA) is a critical pathogen, and its antibiotic resistance is largely driven by the quorum-sensing regulator LasR. Herein, we report the design, synthesis, and characterization of Aqs1C, a mutated peptide derivative of Aqs1, optimized to inhibit LasR and its quorum-sensing pathway. By introducing a targeted mutation, Aqs1C exhibited enhanced stability and binding affinity for LasR protein compared to its predecessor, Aqs1B. Using molecular dynamics simulations (MDS), the Aqs1C-LasR complex demonstrated a marked increase in structural stability, reflected in reduced root mean square deviation (RMSD) values and lower binding free energy. Electrostatic complementarity analysis showed stronger and more favorable interactions between Aqs1C and LasR. Further, GaMD experiments were able to reproduce the binding state between Aqs1C and LasR, indicating the binding mechanism between them. These molecular insights correlated with functional in vitro assays. Aqs1C effectively inhibited quorum-sensing-associated virulence factors in PA, involving biofilm formation (77.6 % inhibition), pyocyanin production (75.7 % inhibition), protease secretion (61.1 % inhibition), and rhamnolipid production (74.1 % inhibition), at a 100 μg/mL concentration, in a comparable or superior pattern to azithromycin (AZM). Molecular modelling, MDS, and GaMD insights and in vitro assays established Aqs1C as a promising candidate for therapeutic development to mitigate PA infections through targeted quorum-sensing disruption.

Titanium dioxide nanoparticles (TiO2 NPs) have attracted significant attention for their unique physicochemical features and various applications. This study demonstrated the biosynthesis of TiO2 NPs using Aspergillus fungal extract that served as a green and eco-friendly reducing and stabilizing agent. The biosynthesized nanoparticles were analyzed using SEM and TEM to determine their morphology, size, and distribution, FTIR to determine functional groups, and Zeta potential to assess their surface charge and stability. An extensive review of the Protein Data Bank (PDB) and literature indicated that TiO2 could target various cancer-relevant matrix metalloproteinases. In vitro screening indicated promising anticancer effects against the MCF7 breast cancer cell line. To investigate the possible mode of action of TiO2 NPs as an anticancer agent, human matrix metalloproteinase-3 was highlighted as a protein inhibited by metallic ions like PtCl2. Therefore, we investigated whether TiO2 could similarly interact with the active site of MMP-3. We hypothesized that TiO2 could interact with the MMP-3 active site and replace PtCl2 with modelled TiO2 in its co-crystallized binding site. A 100 ns-long MDS, binding free energy (Delta GBinding) of PtCl2 and TiO2 within MMP-3 binding site indicated that TiO2's enhanced binding affinity and stability, as evidenced by a Delta GBinding of-7.23 kcal/mol and average RMSD of 0.89 & Aring;, compared to PtCl2's lower affinity. In conclusion, endophytic fungi can be used efficiently in the biosynthesis of nanoparticles. Our study indicated TiO2 NPs have a potential anticancer effect, suggesting TiO2 binds to MMP3, potentially offering comparable inhibitory effects on the enzyme's activity.

Chamaerops humilis L. is clumping palm of the family Arecaceae with promising health-promoting effects. Parts of this species are utilized as food and employed in folk medicine to treat several disorders. This study investigated the phytochemical constituents of C. humilis leaves and their antioxidant and xanthine oxidase (XO) inhibitory activities in vitro and in vivo in acetaminophen (APAP)-induced hepatotoxicity in rats. The chemical structure of the isolated phytochemicals was determined using data obtained from UV, MS, IR, and 1H-, 13C-NMR spectroscopic tools as well as comparison with authentic markers. Eleven compounds, including tricin 7-O-β-rutinoside, vicenin, tricin, astragalin, borassoside D, pregnane-3,5,6,16-tetrol, oleanolic acid, β-sitosterol and campesterol were isolated from C. humilis ethanolic extract (CHEE). CHEE and the butanol, n-hexane, and dichloromethane fractions exhibited in vitro radical scavenging and XO inhibitory efficacies. The computational findings revealed the tendency of the isolated compounds towards the active site of XO. In vivo, CHEE ameliorated liver function markers and prevented tissue injury induced by APAP in rats. CHEE suppressed hepatic XO, decreased serum uric acid and liver malondialdehyde (MDA), and enhanced reduced glutathione (GSH), superoxide dismutase (SOD), and catalase in APAP-treated rats. CHEE ameliorated serum tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β in APAP-treated rats. Thus, C. humilis is rich in beneficial phytochemicals that possess binding affinity towards XO. C. humilis exhibited potent in vitro antioxidant and XO inhibitory activities, and prevented APAP hepatotoxicity by attenuating tissue injury, oxidative stress and inflammation.

Abstract Background Fagonia cretica L. (Family: Zygophyllaceae), is a wild shrub mostly found in Mediterranean districts and extensively used in folk medicine for a vast array of purposes such as antidiabetic and anticancer during the early stages. The goal of the current study was to validate the antioxidant, anti-inflammatory, and cytotoxic properties of Egyptian F. cretica using in vitro studies, metabolic profiling, and in silico approaches. Methods The plant was collected from the Egyptian desert and the alcoholic extract was prepared from its aerial parts, total phenolic and total flavonoid contents were evaluated spectrophotometrically. Antioxidant potential was assessed via 1,1 diphenyl-2-picrylhydrazyl (DPPH) scavenging activity. Anti-inflammatory activity was validated through in vitro COX-2, COX-1, and nitric oxide inhibition. Cytotoxicity was tested against liver (HepG2), breast (MCF-7), and intestinal (CACO2) carcinoma cell lines followed by assessment of its impact on the levels of apoptotic markers namely topoisomerase I and caspase 9 enzymes. Chemical profiling of the extract was performed using LC-HRMS technique. Saponin rich extract was prepared and tested for affecting topo I and caspase 9 enzymes. In silico studies were conducted on anti-inflammatory (COX-2 and COX-1) and cytotoxicity (topoisomerases I, IIα, and IIβ) targets using Autodock vina in PyRx platform. Results Total phenolic and total flavonoid content of the extract were 2.4 ± 0.12 mg GAE/g and 0.18 ± 0.01 mg RE/g, respectively. In vitro results revealed antioxidant activity calculated as 1.4 ± 0.1 mg AEAC/g. In vitro anti-inflammatory assays unveiled inhibition of COX-2 and COX-1 enzymes with IC50 values of 13.02 ± 0.61 and 26.51 ± 0.83 µg/ml, respectively and nitric oxide with IC50 of 147.05 ± 9.61 µg/ml. Cytotoxicity on MCF-7, HepG2, and CACO2 cell line with IC50 values of 6.9 ± 0.53, 7.6 ± 0.42, and 9.2 ± 0.35 µg/ml, respectively, in addition to in vitro topoisomerase I inhibition (IC50 = 13.57 ± 0.71 µg/ml) and caspase 9 induction by 5.66 folds. Metabolic profiling using LC-HRMS technique resulted in dereplication of 21 compounds including triterpenoid saponins, flavonoids, diterpenoids, etc. Interestingly, saponin rich fraction and non-saponin fraction exhibited similar effects on topoisomerase I and caspase 9. In silico investigation unveiled high binding affinities of almost all the detected metabolites to the active sites of COX-2, COX-1, topo I, IIα, and IIβ enzymes. Conclusion Collectively, we can conclude that F. cretica is a new source of many phytochemicals, and a significant natural source as cytotoxic and anti-inflammatory agent.

Pim-1 kinase, a serine/threonine kinase, is often overexpressed in various cancers, contributing to disease progression and poor prognosis. In this study, we explored the potential of flavonoids as inhibitors of Pim-1 kinase using a combination of molecular docking and steered molecular dynamics (SMD) simulations. Our docking studies revealed two main binding orientations for the flavonoid molecules. The SMD simulations showed that the binding mode with higher pulling forces was linked to stronger inhibitory activity, with a strong positive correlation (R2 ≈ 0.92) between pulling forces and IC50 values. Quercetin stood out as the most potent inhibitor, showing a pulling force of about 820 pN and an IC_(5) 0 of less than 6 µM. Further dynamic simulations indicated that quercetin’s hydroxyl groups at the C3, C-5 and C-7 positions formed stable hydrogen bonds with key residues GLU-121, Leu-44 and Val-126, respectively enhancing its binding stability and effectiveness. Our results emphasized the critical role of the hydroxyl group at the C-3 position, which plays a pivotal function in effectively anchoring these molecules in the active site of Pim-1 kinase. Principal component analysis (PCA) of Pim-1 kinase’s conformational changes revealed that potent inhibitors like quercetin, galangin, and kaempferol significantly restricted the enzyme’s flexibility, suggesting potential inhibitory effect. These findings provide insights into the structural interactions between flavonoids and Pim-1 kinase, offering a foundation for future experimental investigations. However, further studies, including in vitro and in vivo validation, are necessary to assess the pharmacological relevance and specificity of flavonoids in cancer therapy.

The anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV -vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and antibiofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli . In conclusion, depending on their bioactive metabolites, P. lamellosa- derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads.

Background: Itraconazole (ITZ) is an antiangiogenic agent recognized as a potent suppressor of endothelial cell growth that suppresses angiogenesis. Nevertheless, its exploitation is significantly restricted by its low bioavailability and systematic side effects. The objective of this study was to utilize glycerosomes (GLY), glycerol-developed vesicles, as innovative nanovesicles for successful ITZ pulmonary drug delivery. Methods: The glycerosomes were functionalized with hyaluronic acid (HA-GLY) to potentiate the anticancer efficacy of ITZ and extend its local bio-fate. ITZ-HA-GLY were fabricated using soybean phosphatidylcholine, tween 80, HA, and sonication time via a thin-film hydration approach according to a 24 full factorial design. The impact of formulation parameters on ITZ-HA-GLY physicochemical properties, as well as the optimal formulation option, was evaluated using Design-Expert®. Sulphorhodamine-B (SRB) colorimetric cytotoxicity assay of the optimized ITZ-HA-GLY versus ITZ suspension was explored in the human A549 cell line. The in vivo pharmacokinetics and bio-distribution examined subsequent to intratracheal administrations of ITZ suspension, and ITZ-HA-GLY were scrutinized in rats. Results: The optimized ITZ-HA-GLY unveiled vesicles of size 210.23 ± 6.43 nm, zeta potential of 41.06 ± 2.62 mV, and entrapment efficiency of 73.65 ± 1.76%. Additionally, ITZ-HA-GLY manifested a far lower IC50 of 13.03 ± 0.2 µg/mL on the A549 cell line than that of ITZ suspension (28.14 ± 1.6 µg/mL). Additionally, the biodistribution analysis revealed a higher concentration of ITZ-HA-GLY within the lung tissues by 3.64-fold as compared to ITZ suspension. Furthermore, the mean resistance time of ITZ-HA-GLY declined more slowly with 14 h as compared to ITZ suspension, confirming the accumulation of ITZ inside the lungs and their promising usage as a target for the treatment of lung disease. Conclusions: These data indicate that the improved ITZ-HA-GLY demonstrates significant promise and represents an exciting prospect in intratracheal delivery systems for lung cancer treatment, meriting further investigation.

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC50 =3.3, 4.2 and 6.8 μg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.

AbstractMetabolites exploration of the ethyl acetate extract of Fusarium solani culture broth that was isolated from Euphorbia tirucalli root afforded five compounds; 4-hydroxybenzaldehyde (1), 4-hydroxybenzoic acid (2), tyrosol (3), azelaic acid (4), malic acid (5), and fusaric acid (6). Fungal extract as well as its metabolites were evaluated for their anti-inflammatory and anti-hyperpigmentation potential via in vitro cyclooxygenases and tyrosinase inhibition assays, respectively. Azelaic acid (4) exhibited powerful and selective COX-2 inhibition followed by fusaric acid (6) with IC50 values (2.21 ± 0.06 and 4.81 ± 0.14 μM, respectively). As well, azelaic acid (4) had the most impressive tyrosinase inhibitory effect with IC50 value of 8.75 ± 0.18 μM compared to kojic acid (IC50 = 9.27 ± 0.19 μM). Exclusive computational studies of azelaic acid and fusaric acid with COX-2 were in good accord with the in vitro results. Interestingly, this is the first time to investigate and report the potential of compounds 3–6 to inhibit cyclooxygenase enzymes. One of the most invasive forms of skin cancer is melanoma, a molecular docking study using a set of enzymes related to melanoma suggested pirin to be therapeutic target for azelaic acid and fusaric acid as a plausible mechanism for their anti-melanoma activity.

Terminalia arjuna tree is an important plant with massive traditional uses. This study aims to carry out a comparative phytochemical and biological evaluation on the leaves, flowers, and bark of T. arjuna. Phytochemical analysis involved exploration of the methanolic extracts using GC/MS technique as well as quantitative determination of the phenolic and flavonoid contents using Folin–Ciocalteu and AlCl3 reagents, respectively. In vitro biological evaluation of the different extracts as antioxidant and anticholinesterase were studied. Reducing power assay and 2,2-diphenyl-1-picrylhydrazyl (DPPH) were used to evaluate the antioxidant activity while anticholinesterase activity of the extracts was measured by Ellman’s reagent at two concentrations, 10 and 100 μg/ml. Results revealed that the bark extract has the highest phenolic content 250.3 ± 17.3 mg/GAE/g dry sample, the leaves has the highest flavonoid content 5.03 ± 1.18 mg/RE/g dry sample. GC/MS results implied the identification of twenty-six, seventeen and five compounds in flowers, bark and leaves, respectively. Methyl palmitate (30.79

Genus Salsola (family Amaranthaceae) is one of the most prevailing genera in Saudi Arabia. Although several species were reported for their traditional uses, the majority of Salsola species still need to be phytochemically and biologically explored. The current study presents the GC-MS profiling as well as an in vitro investigation of the bioactivities of the n-hexane extracts from the five Salsola species: Salsola arabica, S. cyclophylla, S. imbricata, S. incanescens and S. villosa. Additionally, the compounds identified in the most active extracts were screened for their interaction with the active sites of cyclooxygenase enzyme isoforms (COX-1 and COX-2). GC-MS analysis of the n-hexane extracts from the five species resulted in the identification of 67 constituents. Oleic acid (75.57%), 1-octadecene (14.46%), cinnamaldehyde α-hexyl (57.15%), octacosyl heptafluorobutyrate (25.36%) and hexadecanoic acid methyl ester (26.15%) represent the major constituents in S. arabica, S. cyclophylla, S. imbricata, S. inscanescence and S. villosa, respectively. Results of bioactivity testing highlighted S. villosa as having the highest anti-oxidant activity (IC50 0.99 ± 0.05 mg/mL), which was closely followed by S. cyclophylla (IC50 1.36 ± 0.06 mg/mL) compared to the IC50 of 0.16 ± 0.01 mg/mL recorded by ascorbic acid. S. villosa was further noted for having the strongest COX-2 inhibitory activity (IC50 4.6 ± 0.13 µg/mL) among the tested extracts followed by S. arabica (IC50 13.1 ± 0.37 µg/mL) and S. cyclophylla (IC50 20.1 ± 0.57 µg/mL). On the other hand, S. imbricata extract displayed the most characteristic inhibition activity against COX-1 (IC50 10.2 ± 0.52 µg/mL), which was non-significant from the standard drug celecoxib. Based upon bioactivity results, the phytoconstituents identified in S. villosa and S. imbricata extracts were investigated for their capability to interact with the active sites of both cyclooxygenase enzyme isoforms adopting molecular docking. Results indicated the possibility to incorporate the compounds to active sites of the enzymes where some of them bind with their polar end into the cavity beyond Arg120 and their aliphatic chain oriented to the catalytically important Tyr385 similar to the natural substrate arachidonic acid, indicating that they could be promising candidates for the future development of selective COX inhibitors.