Chemical Characterization of Phoenix dactylifera L. Seeds and their Beneficial Effects on the Vascular Response in Hypertensive Rats.

Although Phoenix dactylifera dates are traditionally consumed for their health benefits, no research has been done on the vascular response in hypertensive animals. This study evaluated the vascular relaxation of hydroalcoholic extracts from seeds of three varieties of P. dactylifera; Sukkari seed (SS), Ajwa seed (AS), and Mabroom seed (MS) on L-NAME-induced hypertension and spontaneously hypertensive rats (SHR). Results showed that all extracts (10 µg/mL) caused relaxations higher than 60% in the aortic rings precontracted with 10- 6 M phenylephrine in normotensive rats, the SS extract was the most potent. Endothelial nitric oxide (NO) pathway is involved as significantly reduced vascular relaxation in denuded-endothelium rat aorta and with an inhibitor (10- 4 M L-Nω-Nitro arginine methyl ester; L-NAME) of endothelial nitric oxide synthase (eNOS). Confocal microscopy confirmed that 10 µg/mL SS extract increases NO generation as detected by DAF-FM fluorescence in intact aortic rings. Consistent with these findings, vascular relaxation in intact aortic rings at 10 µg/mL SS extract was significantly decreased in L-NAME-induced hypertensive rats (endothelial dysfunction model), but not in SHR. In both hypertensive models, the denuded endothelium blunted the vascular relaxation. In conclusion, the hydroalcoholic extract of the seed of P. dactylifera (Sukkari, Ajwa and Mabroom varieties) presents a potent endothelium-dependent vascular relaxation, via NO, in normotensive rats as well as in two different models of hypertension. This effect could be mediated by the presence of phenolic compounds identified by UHPLC-ESI-MS/MS, such as protocatechuic acid, and caftaric acid.

Diabetes-related lower limb wounds: Antibiotic susceptibility pattern and biofilm formation.

The expeditious incidence of diabetes mellitus in Riyadh, Saudi Arabia, there is a significant increase in the total number of people with diabetic foot ulcers. For diabetic lower limb wound infections (DLWs) to be effectively treated, information on the prevalence of bacteria that cause in this region as well as their patterns of antibiotic resistance is significant. Growing evidence indicates that biofilm formers are present in chronic DFU and that these biofilm formers promote the emergence of multi-drug antibiotic resistant (MDR) strains and therapeutic rejection. The current study targeted to isolate bacteria from wounds caused by diabetes specifically at hospitals in Riyadh and assess the bacterium's resistance to antibiotics and propensity to develop biofilms. Totally 63 pathogenic microbes were identified from 70 patients suffering from DFU. Sixteen (25.4%) of the 63 bacterial strains were gram-positive, and 47 (74.6%) were gram-negative. Most of the gram-negative bacteria were resistant to tigecycline, nitrofurantoin, ampicillin, amoxicillin, cefalotin, and cefoxitin. Several gram-negative bacteria are susceptible to piperacillin, meropenem, amikacin, gentamicin, imipenem, ciprofloxacin, and trimethoprim. The most significant antibiotic that demonstrated 100% susceptibility to all pathogens was meropenem. Serratia marcescens and Staphylococcus aureus were shown to have significant biofilm formers. MDR bacterial strains comprised about 87.5% of the biofilm former strains. To the best of our knowledge, Riyadh, Saudi Arabia is the first region where Serratia marcescens was the most common bacteria from DFU infections. Our research findings would deliver information on evidence-based alternative strategies to develop effective treatment approaches for DFU treatment.

Discovery and structural assignment of (S)-sydosine from amphipod-derived Aspergillus sydowii MBC15-11F through HRMS, advanced Mosher, and molecular modelling analyses.

AIMS: This study aims to prioritize fungal strains recovered from under-explored habitats that produce new metabolites. HRMS dereplication is used to avoid structure redundancy, and molecular modelling is used to assign absolute configuration. METHODS AND RESULTS: MBC15-11F was isolated from an amphipod and identified using ITS, 28S, and ß-tubulin phylogeny as Aspergillus sydowii. Chemical profiling using taxonomic-based dereplication identified structurally diverse metabolites, including unreported ones. Large-scale fermentation led to the discovery of a new N-acyl adenosine derivative: (S)-sydosine (1) which was elucidated by NMR and HRESIMS analyses. Two known compounds were also identified as predicted by the initial dereplication process. Due to scarcity of 1, molecular modelling was used to assign its absolute configuration without hydrolysis, and is supported by advanced Mosher derivatization. When the isolated compounds were assessed against a panel of bacterial pathogens, only phenamide (3) showed anti-Staphylococcus aureus activity. CONCLUSION: Fermentation of A. sydowii yielded a new (S)-sydosine and known metabolites as predicted by HRESIMS-aided dereplication. Molecular modelling prediction of the absolute configuration of 1 agreed with advanced Mosher analysis.

Photocatalytic investigation of textile dyes and E. coli bacteria from wastewater using Fe3O4@MnO2 heterojunction and investigation for hydrogen generation on NaBH4 hydrolysis.

Various impurities found nowadays in water can be detrimental to human health. This work focused on utilizing Fe3O4@MnO2 nanocomposite for cleaning organic contaminants from water, including rhodamine B (RhB) and Escherichia coli (E. coli). Analysis methods such as XRD, UV-vis, TEM, and FTIR were used to describe the nanocomposite. The results showed that the developed nanocomposite has good photocatalytic activity against pollutants in wastewater. The E. coli was destroyed after 90 min, and the RhB photodegradation rate was 75%. Moreover, the Fe3O4@MnO2 efficiency as a catalyst for producing hydrogen as an alternative energy source was tested. According to the calculations, the nanomaterial's turnover frequency, activation energy, enthalpy, and entropy are 1061.3 h-1, 28.93 kJ/mol, 26.38 kJ/mol, and -128.41 J/mol.K, respectively. Four reusability tests were completed, and the average reusability was 78%. The obtained data indicated the excellent potential for the developed Fe3O4@MnO2 nanomaterial to act as an adsorbent, thus representing an alternative to the classical depollution methods. This study showed that nanoparticles have a photocatalytic effect against pathogenic bacteria and RhB azo dye in polluted waters and offer an effective catalytic activity to produce hydrogen as an alternative energy source.

Multitarget Potential of Phytochemicals from Traditional Medicinal Tree, Terminalia arjuna (Roxb. ex DC.) Wight & Arnot as Potential Medicaments for Cardiovascular Disease: An In-Silico Approach.

Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. Terminalia arjuna (Roxb. ex DC.) Wight & Arnot of the Combretaceae family is one of the most frequently approved and utilized medicinal trees in the traditional medicinal system, which was used for the treatment of a variety of diseases, including cardiovascular disorders. The present study aims to identify phytochemicals from T. arjuna, that do not exhibit any toxicity and have significant cardioprotective activity using an in-silico technique. Four different cardiovascular proteins, namely human angiotensin receptor (PDB ID: 4YAY), P38 mitogen-activated protein kinase (MAPK, PDB ID: 4DLI), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-Co A) reductase (PDB ID: 1HW9), and human C-reactive protein (PDB ID: 1B09), were used as target proteins to identify potential inhibitors using a virtual screening of the phytochemicals in T. arjuna revealed casuarinin as a potential inhibitor of all selected target proteins with strong binding energy. Furthermore, MD simulations for a 100 ns time scale also revealed that most of the key protein contacts of all target proteins were retained throughout the simulation trajectories. Binding free energy calculations using the MM-GBSA approach also support a strong inhibitory effect of casuarinin on target proteins. Casuarinin's effective binding to these proteins lays the groundwork for the development of broad-spectrum drugs as well as the understanding of the underlying mechanism against cardiovascular diseases through in vivo and clinical studies.

Efficient Synthesis of Imine-Carboxylic Acid Functionalized Compounds: Single Crystal, Hirshfeld Surface and Quantum Chemical Exploration.

Two aminobenzoic acid based crystalline imines (HMBA and DHBA) were synthesized through a condensation reaction of 4-aminobenzoic acid and substituted benzaldehydes. Single-crystal X-ray diffraction was employed for the determination of structures of prepared Schiff bases. The stability of super molecular structures of both molecules was achieved by intramolecular H-bonding accompanied by strong, as well as comparatively weak, intermolecular attractive forces. The comparative analysis of the non-covalent forces in HMBA and DHBA was performed by Hirshfeld surface analysis and an interaction energy study between the molecular pairs. Along with the synthesis, quantum chemical calculations were also accomplished at M06/6-311G (d, p) functional of density functional theory (DFT). The frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP), natural bond orbitals (NBOs), global reactivity parameters (GRPs) and natural population (NPA) analyses were also carried out. The findings of FMOs found that Egap for HMBA was examined to be smaller (3.477 eV) than that of DHBA (3.7933 eV), which indicated a greater charge transference rate in HMBA. Further, the NBO analysis showed the efficient intramolecular charge transfer (ICT), as studied by Hirshfeld surface analysis.

Chitosan-Coated Solid Lipid Nanoparticles as an Efficient Avenue for Boosted Biological Activities of Aloe perryi: Antioxidant, Antibacterial, and Anticancer Potential.

Aloe perryi (ALP) is an herb that has several biological activities such as antioxidant, antibacterial, and antitumor effects and is frequently used to treat a wide range of illnesses. The activity of many compounds is augmented by loading them in nanocarriers. In this study, ALP-loaded nanosystems were developed to improve their biological activity. Among different nanocarriers, solid lipid nanoparticles (ALP-SLNs), chitosan nanoparticles (ALP-CSNPs), and CS-coated SLNs (C-ALP-SLNs) were explored. The particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency, and release profile were evaluated. Scanning electron microscopy was used to see the nanoparticles' morphology. Moreover, the possible biological properties of ALP were assessed and evaluated. ALP extract contained 187 mg GAE/g extract and 33 mg QE/g extract in terms of total phenolic and flavonoid content, respectively. The ALP-SLNs-F1 and ALP-SLNs-F2 showed particle sizes of 168.7 ± 3.1 and 138.4 ± 9.5 nm and the zeta potential values of -12.4 ± 0.6, and -15.8 ± 2.4 mV, respectively. However, C-ALP-SLNs-F1 and C-ALP-SLNs-F2 had particle sizes of 185.3 ± 5.5 and 173.6 ± 11.3 nm with zeta potential values of 11.3 ± 1.4 and 13.6 ± 1.1 mV, respectively. The particle size and zeta potential of ALP-CSNPs were 214.8 ± 6.6 nm and 27.8 ± 3.4 mV, respectively. All nanoparticles exhibited PDI < 0.3, indicating homogenous dispersions. The obtained formulations had EE% and DL% in the ranges of 65-82% and 2.8-5.2%, respectively. After 48 h, the in vitro ALP release rates from ALP-SLNs-F1, ALP-SLNs-F2, C-ALP-SLNs-F1, C-ALP-SLNs-F2, and ALP-CSNPs were 86%, 91%, 78%, 84%, and 74%, respectively. They were relatively stable with a minor particle size increase after one month of storage. C-ALP-SLNs-F2 exhibited the greatest antioxidant activity against DPPH radicals at 73.27%. C-ALP-SLNs-F2 demonstrated higher antibacterial activity based on MIC values of 25, 50, and 50 µg/mL for P. aeruginosa, S. aureus, and E. coli, respectively. In addition, C-ALP-SLNs-F2 showed potential anticancer activity against A549, LoVo, and MCF-7 cell lines with IC50 values of 11.42 ± 1.16, 16.97 ± 1.93, and 8.25 ± 0.44, respectively. The results indicate that C-ALP-SLNs-F2 may be promising nanocarriers for enhancing ALP-based medicines.

Isochlorogenic Acid Glucosides from the Arabian Medicinal Plant Artemisia sieberi and Their Antimicrobial Activities.

A phytochemical investigation of the stems of the Arabian plant Artemisia sieberi afforded three new isochlorogenic acid derivatives, namely isochlorogenic acid A-3'-O-ß-glucopyranoside (1), isochlorogenic acid A-3'-O-ß-glucopyranoside methyl ester (2), and isochlorogenic acid C-3'-O-ß-glucopyranoside (3), obtained along with thirteen known secondary metabolites belonging to distinct structural classes. The structures of the new metabolites were elucidated by modern spectroscopic techniues based on high-resolution mass spectrometry (HR-ESIMS) and 1D/2D nuclear magnetic resonance (NMR). All isolated compounds were tested for their potential antimicrobial activity against four different bacterial strains (Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa), in addition to a fungal strain (Candida tropicalis), The results were expressed as the diameter of the clear zone (in millimetres) around each well. Compounds 1 and 3 (isochlorogenic acid A-3'-O-ß-glucopyranoside and isochlorogenic acid C-3'-O-ß-glucopyranoside, respectively) displayed remarkable antifungal effect and potent antibacterial activities against B. subtilis and S. aureus, respectively. 3α,4α-10ß-trihydroxy-8α-acetyloxyguaian-12,6α-olide (6) and angelicoidenol 2-O-ß-d-glucopyranoside (9) emerged as interesting dual antibacterial (selective on P. aeruginosa)/antifungal agents.

Comparative evaluation of the potential anti-spasmodic activity of Piper longum, Piper nigrum, Terminalia bellerica, Terminalia chebula, and Zingiber officinale in experimental animals.

Background: Spasm of muscle is one of the frequent complaints seen by most of the population worldwide. The present study evaluated the efficacy of some of the commonly used herbal extracts against known spasmogens, such as histamine and 5-hydroxytryptamine (5-HT). Material and methods: The study was conducted on isolated guinea pig ileum and rat uterus preparations using histamine and 5-HT, respectively. Five herbal extracts such as Piper longum (P.L), Piper nigrum (P.N), Terminalia bellerica (T.B), Terminalia chebula (T.C), and Zingiber officinale (Z.O) were tested. Herbal extracts at doses 50, 150, 500, 1500, and 5000 mcg/ml were pretreated to the isolated tissue preparation, and the contractile response of histamine and 5-HT was recorded. The efficacy and the inhibitory concentration (IC50) were calculated and statistically analyzed by one-way ANOVA. Results: The study indicated that all five herbal extracts produced a concentration-dependent suppression of histamine and 5-HT-induced responses. A significant (p < 0.05) non-competitive antagonism was observed against the known spasmogen induced smooth muscle contraction for P.L, P.N, T.B, and Z.O in both guinea pigs and rat uterus preparation. Moreover, P.L and P.N completely abolished (100%) the contractile response induced by histamine and 5-HT. Although, T.C produced a concentration-dependent reduction in known spasmogen-induced contraction but the response was found to be statistically non-significant (p greater than 0.05). Conclusion: The finding suggested that P.L. and P.N. have better activity in terms of reducing the spasmogenic contractions compared to other extracts. Additionally, T.B. and Z.O. can lessen the uterine and intestinal contractions brought on by spasmogens. Although P.L and P.N demonstrated better efficacy against the spasmogenic activity of histamine and 5-HT, more research, particularly on isolated phytochemicals of the extracts and involving different experimental models, is required before establishing the precise safety and efficacy against spasmogenic-induced disorders.

Association of cholesterol with hepatorenal markers and quality of life in diabetic patients before and after magnesium and potassium supplements.

Background: Magnesium and potassium are two critical minerals that have been linked to the treatment of diabetes and its consequences. A lack of magnesium has been linked to insulin resistance and diabetes, whereas potassium has been found to promote insulin sensitivity and glucose metabolism. The study aimed to determine the relationship between cholesterol, liver and kidney markers, and quality of life in diabetic patients before and after magnesium and potassium supplementation. Methods: It was a single-blind randomized controlled study at Lahore Garrison University and Lahore Medical Research Centre (LMRC). The study included 200 diabetes participants. Four groups were made based on supplements. Blood samples of all diabetes patients were obtained to assess their quality of life before and after using Mg + and K + supplements, as well as the association between cholesterol, liver, and kidney markers. Results: The participants' average age was 51.0 ± 11.08. 139 (69.5 %) of the 200 participants were female, whereas 26 (30.5 %) were male. There was no correlation between the quality of life measure and the patients' cholesterol levels before and after the magnesium and potassium supplementation. Furthermore, the kidney and liver indicators were not dependent on the diabetes individuals' cholesterol levels. Conclusions: The study concluded that none of the four groups noticed a significant effect of magnesium and potassium therapies on the patient's quality of life or cholesterol levels. However, more research is needed to determine if liver and kidney problems are linked to cholesterol levels before and after medication, as the current study found no significant correlation between the two parameters.

Neoechinulin A as a Promising SARS-CoV-2 Mpro Inhibitor: In Vitro and In Silico Study Showing the Ability of Simulations in Discerning Active from Inactive Enzyme Inhibitors.

The COVID-19 pandemic and its continuing emerging variants emphasize the need to discover appropriate treatment, where vaccines alone have failed to show complete protection against the new variants of the virus. Therefore, treatment of the infected cases is critical. This paper discusses the bio-guided isolation of three indole diketopiperazine alkaloids, neoechinulin A (1), echinulin (2), and eurocristatine (3), from the Red Sea-derived Aspergillus fumigatus MR2012. Neoechinulin A (1) exhibited a potent inhibitory effect against SARS-CoV-2 Mpro with IC50 value of 0.47 µM, which is comparable to the reference standard GC376. Despite the structural similarity between the three compounds, only 1 showed a promising effect. The mechanism of inhibition is discussed in light of a series of extensive molecular docking, classical and steered molecular dynamics simulation experiments. This paper sheds light on indole diketopiperazine alkaloids as a potential structural motif against SARS-CoV-2 Mpro. Additionally, it highlights the potential of different molecular docking and molecular dynamics simulation approaches in the discrimination between active and inactive structurally related Mpro inhibitors.

Evaluation of the Antifungal, Antioxidant, and Anti-Diabetic Potential of the Essential Oil of Curcuma longa Leaves from the North-Western Himalayas by In Vitro and In Silico Analysis.

Essential oils (EOs) have gained immense popularity due to considerable interest in the health, food, and pharmaceutical industries. The present study aimed to evaluate the antimicrobial and antioxidant activity and the anti-diabetic potential of Curcuma longa leaf (CLO) essential oil. Further, major phytocompounds of CLO were analyzed for their in-silico interactions with antifungal, antioxidant, and anti-diabetic proteins. CLO was found to have a strong antifungal activity against the tested Candida species with zone of inhibition (ZOI)-11.5 ± 0.71 mm to 13 ± 1.41 mm and minimum inhibitory concentration (MIC) was 0.63%. CLO also showed antioxidant activity, with IC50 values of 5.85 ± 1.61 µg/mL using 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and 32.92 ± 0.64 µM using ferric reducing antioxidant power (FRAP) assay. CLO also showed anti-diabetic activity with an IC50 of 43.06 ± 1.24 µg/mL as compared to metformin (half maximal inhibitory concentration, IC50-16.503 ± 0.66 µg/mL). Gas chromatography-mass spectrometry (GC-MS) analysis of CLO showed the presence of (-)-zingiberene (17.84%); 3,7-cyclodecadien-1-one, 3,7-dimethyl-10-(1-methylethylidene)-(15.31%); cyclohexene, 4-methyl-3-(1-methylethylidene) (12.47%); and (+)-4-Carene (11.89%) as major phytocompounds. Molecular docking of these compounds with antifungal proteins (cytochrome P450 14 alpha-sterol demethylase, PDB ID: 1EA1, and N-myristoyl transferase, PDB ID: 1IYL), antioxidant (human peroxiredoxin 5, PDB ID: 1HD2), and anti-diabetic proteins (human pancreatic alpha-amylase, PDB ID: 1HNY) showed strong binding of 3,7-cyclodecadien-1-one with all the selected protein targets. Furthermore, molecular dynamics (MD) simulations for a 100 ns time scale revealed that most of the key contacts of target proteins were retained throughout the simulation trajectories. Binding free energy calculations using molecular mechanics generalized born surface area (MM/GBSA), and drug-likeness and toxicity analysis also proved the potential for 3,7-cyclodecadien-1-one, 3,7-dimethyl-10-(1-methylethylidene) to replace toxic synthetic drugs and act as natural antioxidants.

Antimicrobial Activity of Dihydroisocoumarin Isolated from Wadi Lajab Sediment-Derived Fungus Penicillium chrysogenum: In Vitro and In Silico Study.

Antibiotic resistance is considered a major health concern globally. It is a fact that the clinical need for new antibiotics was not achieved until now. One of the most commonly prescribed classes of antibiotics is ß-Lactam antibiotics. However, most bacteria have developed resistance against ß-Lactams by producing enzymes ß-Lactamase or penicillinase. The discovery of new ß-Lactamase inhibitors as new antibiotics or antibiotic adjuvants is essential to avoid future catastrophic pandemics. In this study, five dihydroisocoumarin: 6-methoxy mellein (1); 5,6-dihydroxymellein (2); 6-hydroxymellein (3); 4-chloro-6-hydroxymellein (4) and 4-chloro-5,6-di-hydroxymellein (5) were isolated from Wadi Lajab sediment-derived fungus Penicillium chrysogenum, located 15 km northwest of Jazan, KSA. The elucidation of the chemical structures of the isolated compounds was performed by analysis of their NMR, MS. Compounds 1-5 were tested for antibacterial activities against Gram-positive and Gram-negative bacteria. All of the compounds exhibited selective antibacterial activity against Gram-positive bacteria Staphylococcus aureus and Bacillus licheniformis except compound 3. The chloro-dihydroisocoumarin derivative, compound 4, showed potential antimicrobial activities against all of the tested strains with the MIC value between 0.8-5.3 µg/mL followed by compound 5, which exhibited a moderate inhibitory effect. Molecular docking data showed good affinity with the isolated compounds to ß-Lactamase enzymes of bacteria; NDM-1, CTX-M, OXA-48. This work provides an effective strategy for compounds to inhibit bacterial growth or overcome bacterial resistance.

Biodiesel Production from Alkali-Catalyzed Transesterification of Tamarindus indica Seed Oil and Optimization of Process Conditions.

Biodiesel is considered a sustainable alternative to petro-diesel owing to several favorable characteristics. However, higher production costs, primarily due to the use of costly edible oils as raw materials, are a chief impediment to its pecuniary feasibility. Exploring non-edible oils as raw material for biodiesel is an attractive strategy that would address the economic constraints associated with biodiesel production. This research aims to optimize the reaction conditions for the production of biodiesel through an alkali-catalyzed transesterification of Tamarindus indica seed oil. The Taguchi method was applied to optimize performance parameters such as alcohol-to-oil molar ratio, catalyst amount, and reaction time. The fatty acid content of both oil and biodiesel was determined using gas chromatography. The optimized conditions of alcohol-to-oil molar ratio (6:1), catalyst (1.5% w/w), and reaction time 1 h afforded biodiesel with 93.5% yield. The most considerable contribution came from the molar ratio of alcohol to oil (75.9%) followed by the amount of catalyst (20.7%). In another case, alcohol to oil molar ratio (9:1), catalyst (1.5% w/w) and reaction time 1.5 h afforded biodiesel 82.5% yield. The fuel properties of Tamarindus indica methyl esters produced under ideal conditions were within ASTM D6751 biodiesel specified limits. Findings of the study indicate that Tamarindus indica may be chosen as a prospective and viable option for large-scale production of biodiesel, making it a substitute for petro-diesel.

Design, Synthesis, and Biological Evaluation of Novel Dihydropyridine and Pyridine Analogs as Potent Human Tissue Nonspecific Alkaline Phosphatase Inhibitors with Anticancer Activity: ROS and DNA Damage-Induced Apoptosis.

Small molecules with nitrogen-containing scaffolds have gained much attention due to their biological importance in the development of new anticancer agents. The present paper reports the synthesis of a library of new dihydropyridine and pyridine analogs with diverse pharmacophores. All compounds were tested against the human tissue nonspecific alkaline phosphatase (h-TNAP) enzyme. Most of the compounds showed excellent enzyme inhibition against h-TNAP, having IC50 values ranging from 0.49 ± 0.025 to 8.8 ± 0.53 µM, which is multi-fold higher than that of the standard inhibitor (levamisole = 22.65 ± 1.60 µM) of the h-TNAP enzyme. Furthermore, an MTT assay was carried out to evaluate cytotoxicity against the HeLa and MCF-7 cancer cell lines. Among the analogs, the most potent dihydropyridine-based compound 4d was selected to investigate pro-apoptotic behavior. The further analysis demonstrated that compound 4d played a significant role in inducing apoptosis through multiple mechanisms, including overproduction of reactive oxygen species, mitochondrial dysfunction, DNA damaging, and arrest of the cell cycle at the G1 phase by inhibiting CDK4/6. The apoptosis-inducing effect of compound 4d was studied through staining agents, microscopic, and flow cytometry techniques. Detailed structure-activity relationship (SAR) and molecular docking studies were carried out to identify the core structural features responsible for inhibiting the enzymatic activity of the h-TNAP enzyme. Moreover, fluorescence emission studies corroborated the binding interaction of compound 4d with DNA through a fluorescence titration experiment.

An Anti-Inflammatory 2,4-Cyclized-3,4-Secospongian Diterpenoid and Furanoterpene-Related Metabolites of a Marine Sponge Spongia sp. from the Red Sea.

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (-)-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3ß,5α-diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 µM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

Antiproliferative Illudalane Sesquiterpenes from the Marine Sediment Ascomycete Aspergillus oryzae.

The new asperorlactone (1), along with the known illudalane sesquiterpene echinolactone D (2), two known pyrones, 4-(hydroxymethyl)-5-hydroxy-2H-pyran-2-one (3) and its acetate 4, and 4-hydroxybenzaldehyde (5), were isolated from a culture of Aspergillus oryzae, collected from Red Sea marine sediments. The structure of asperorlactone (1) was elucidated by HR-ESIMS, 1D, and 2D NMR, and a comparison between experimental and DFT calculated electronic circular dichroism (ECD) spectra. This is the first report of illudalane sesquiterpenoids from Aspergillus fungi and, more in general, from ascomycetes. Asperorlactone (1) exhibited antiproliferative activity against human lung, liver, and breast carcinoma cell lines, with IC50 values < 100 µM. All the isolated compounds were also evaluated for their toxicity using the zebrafish embryo model.

Penipyranicins A-C: Antibacterial Methylpyran Polyketides from a Hydrothermal Spring Sediment Penicillium sp.

Four new aromatic polyketides (1-4) were isolated from Penicillium sp. RO-11, obtained from the sediment of a hydrothermal spring in the southwestern region of Saudi Arabia. The new compounds are penipyranicins A-C (1-3), characterized by a 4-methyl-4H-pyran moiety, a structural motif unprecedented among fungal polyketides, and the naphthopyrone derivative isopyrenulin (4). The structures of the new compounds were elucidated on the basis of data from mass spectrometry, 1D and 2D NMR analysis, and comparison between experimental and time-dependent density functional theory-calculated electronic circular dichroism spectra. A plausible biosynthetic pathway connecting penipyranicins and isopyrenulin is proposed. The isolated compounds were active against Gram-positive and Gram-negative bacteria.

Epigenetic Modifiers Affect the Bioactive Compounds Secreted by an Endophyte of the Tropical Plant Piper longum.

Seven endophytic fungi were isolated from the tropical medicinal plant Piper longum L. After preliminary screening, Phomopsis heveicola was selected for the epigenetic activation treatments. The antibacterial, antifungal, and antioxidant potentials of crude extracts obtained from the treatments (with and without epigenetic modifiers) were analyzed in vitro. The extracts inhibited growth of the human pathogens Pseudomonas aeruginosa, Shigella sonnei, Streptococcus pyogenes, and Salmonella typhi, as well as the phytopathogens Puccinia recondita, Rhizoctonia solani, Phytophthora infestans, and Botrytis cinerea. Furthermore, DPPH-scavenging activity was higher in valproic acid treated extracts. Volatile chemicals with known biological activities (measured with GC-MS/MS), were released in the valproic acid treatment. The antimicrobial potentials of the extracts were confirmed using MRM/MS analysis. The experiments revealed a new promising endophytic fungus, P. heveicola, to be utilized in biological plant protection and in biomedical applications.

Antibacterial and Antifungal Sesquiterpenoids from Aerial Parts of Anvillea garcinii.

Two new sesquiterpenoids belonging to the guaiane, 4α,9α,10α-trihydroxyguaia-11(13)en-12,6α-olide (1), and germacrane, 9ß-hydroxyparthenolide-9-O-ß-D-glucopyranoside (2), classes have been isolated from the leaves of the Saudi medicinal plant Anvillea garcinii along with seven known compounds (3-9). The structures of the new metabolites were elucidated by spectroscopic analysis, including one-dimensional (1D) and two-dimensional (2D) Nuclear Magnetic Resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HR-ESIMS). The antimicrobial properties of 1-9 were screened against seven different pathogenic microbes, and compounds 1-3 showed a potent antifungal activity.