Targeted Therapy with Cisplatin-Loaded Calcium Citrate Nanoparticles Conjugated with Epidermal Growth Factor for Lung Cancer Treatment.

Lung cancer is the leading cause of cancer-related deaths worldwide with high incidence rates for new cases. Conventional cisplatin (CDDP) therapy has limitations due to severe side effects from nonspecific targeting. To address this challenge, nanomedicine offers targeted therapies. In this study, cisplatin-loaded calcium citrate nanoparticles conjugated with epidermal growth factor (CaCit@CDDP-EGF NPs) were synthesized. The resulting nanodrug had a size below 350 nm with a cation charge. Based on density functional theory (DFT), the CaCit@CDDP NP model containing two citrates substituted on two chlorides exhibited a favorable binding energy of -5.42 eV, and the calculated spectrum at 261 nm closely matched the experimental data. CaCit@CDDP-EGF NPs showed higher inhibition rates against EGFR-expressed and mutant carcinoma cells compared to those of cisplatin while displaying lower cytotoxicity to lung fibroblast cells. Integrating in vitro experiments with in silico studies, these nanoparticles hold promise as a novel nanomedicine for targeted therapy in clinical applications.

Molecular binding of different classes of organophosphates to methyl parathion hydrolase from Ochrobactrum species.

Methyl parathion hydrolase (MPH) is an enzyme of the metallo-ß-lactamase superfamily, which hydrolyses a wide range of organophosphates (OPs). Recently, MPH has attracted attention as a promising enzymatic bioremediator. The crystal structure of MPH enzyme shows a dimeric form, with each subunit containing a binuclear metal ion center. MPH also demonstrates metal ion-dependent selectivity patterns. The origins of these patterns remain unclear but are linked to open questions about the more general role of metal ions in functional evolution and divergence within enzyme superfamilies. We aimed to investigate and compare the binding of different OP pesticides to MPH with cobalt(II) metal ions. In this study, MPH was modeled from Ochrobactrum sp. with different OP pesticides bound, including methyl paraoxon and dichlorvos and profenofos. The docked structures for each substrate optimized by DFT calculation were selected and subjected to atomistic molecular dynamics simulations for 500 ns. It was found that alpha metal ions did not coordinate with all the pesticides. Rather, the pesticides coordinated with less buried beta metal ions. It was also observed that the coordination of beta metal ions was perturbed to accommodate the pesticides. The binding free energy calculations and structure-based pharmacophore model revealed that all the three substrates could bind well at the active site. However, profenofos exhibit a stronger binding affinity to MPH in comparison to the other two substrates. Therefore, our findings provide molecular insight on the binding of different OP pesticides which could help us design the enzyme for OP pesticides degradation.

Enhanced Electrocatalytic CO2 Reduction Reactivity of S- and N-Doped Fe-Embedded Graphene.

In this work, we studied the reaction mechanisms for CO2 reduction reaction (CRR) on the iron-doped graphene and its coordinating sulfur (S) and nitrogen (N) variants, FeNn S4-n (n=1-4), using density functional theory calculations. Our results revealed that the electronic property and catalytic reactivity of the surfaces can be tuned by varying the N and S atoms ratio. The CRR activities of the mixed surfaces, FeN3 S1 , FeN2 S2 , and FeN1 S3 , were better than FeN4 and FeS4 , where the absolute value of the limiting potential of the mixed surface decreased by 0.3 V. Considering the stability, we suggest FeN3 S surface to be favorable for CRR. For the bare surfaces, we found a positive linear correlation between the magnetic moment and the charge of Fe metal. For these surfaces, the reduction of CO (*CO+(H+ +e- )→*CHO) was important in deciding the limiting potential. We found that the adsorption energy of CO displayed a volcano relationship with the magnetic moment of the Fe atom. The study showed that the change of local coordinating structure around the Fe atom could modify the electronic and magnetic properties of the active Fe center and improve the CRR activity performance.

Theoretical study of metal-free catalytic for catalyzing CO-oxidation with a synergistic effect on P and N co-doped graphene.

P and N co-doped graphene (PNxCy-G with x = 1, 2, 3 and y = 0, 1, 2) is designed to enhance graphene reactivity with a synergistic effect of the P and N atoms for the CO oxidation reaction, focusing on the influence of the N dopant concentration on graphene. The calculated results indicate that increasing two or three coordinated N to P can facilitate charge transfer from the surface onto O2 molecules. However, the adsorbed O2 molecule breaks apart on PN3-G surface, affecting CO oxidation performance. Furthermore, PN2C1-G exhibits excellent catalytic activity towards the oxidation of CO via the ER mechanism, which catalyzes CO oxidation with the rate-determining step of only 0.26 eV for the first and 0.25 eV for the second oxidation at 0 K. Additionally, the catalytic oxidation of PN2C1-G via Eley-Rideal mechanism prefers to occur at room temperature (298.15 K), with a rate-determining step of 0.77 eV. The reaction rates at 298.15 K is calculated to be 5.36 × 1016 mol s-1. The rate constants are obtained according to harmonic transition state theory, which could be supportive for catalytic oxidation of CO on the experiment.

Cytotoxicity and Nitric Oxide Production Inhibitory Activities of Compounds Isolated from the Plant Pathogenic Fungus Curvularia sp.

Chemical investigation of the mycelia of the pathogenic fungus Curvularia sp. which was isolated from a leaf of Dactyloctenium aegyptium (crowfoot grass), resulted in the isolation of a new compound, curvulariahawadride (5), along with five known compounds (1-4, and 6). Their structures were determined on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS. The absolute configuration of 5 was established from experimental and calculated electronic circular dichroism (ECD). Compounds 1, 3, and 5 showed nitric oxide (NO) production inhibitory activity with IC50 values of 53.7, 32.8, and 12.8 µM, respectively. Compounds 2 and 4 showed significant cytotoxicity against lung cancer A549, colorectal cancer SW480, and leukemic K562 cells with an IC50 ranging value of 11.73 to 17.59 µM.

Antibacterial and Antifungal Polyketides from the Fungus Aspergillus unguis PSU-MF16.

Seven new polyketides including a phenol (1), two diphenyl ethers (2 and 3), two depsidones (4 and 5), and two phthalides (6 and 7) were isolated from the fungus Aspergillus unguis PSU-MF16 along with 27 known compounds. Their structures were determined by extensive spectroscopic analysis. The absolute configurations of 1 and 4-7 were established using comparative analyses of calculated and experimental ECD spectra. Among the new metabolites, 2 exhibited the best antimicrobial activity against Staphylococcus aureus, methicillin-resistant S. aureus, and Microsporum gypseum with equal MIC values of 16 µg/mL. In addition, known emeguisin A displayed potent antimicrobial activity against S. aureus, methicillin-resistant S. aureus, and Cryptococcus neoformans with equal MIC values of 0.5 µg/mL, compared with the standard drugs, vancomycin and amphotericin B. The structure-activity relationship study of the isolated compounds for antimicrobial activity is discussed.

New Pyrrolobenzoxazine Sesquiterpenoid Derivatives from the Fungus Talaromyces trachyspermus.

Three new pyrrolobenzoxazine sesquiterpenoids, talatrachyoxazines A - C (1:  - 3: ), together with fourteen known compounds (4:  - 17: ), were isolated from the fungus Talaromyces trachyspermus EU23. Their structures were identified by spectroscopic evidence and mass spectrometry. The absolute configurations of 1:  - 3: were determined by NOESY data and comparison of their calculated and experimental electronic circular dichroism (ECD) spectra. Compound 1: showed cytotoxic activity against HelaS3, KB, HT-29, MCF-7, and HepG2 cell lines with IC50 values of 7, 11, 10, 12, and 10 µM, respectively. Compounds 1: and 14: showed weak antibacterial activity against the gram-positive bacteria Bacillus cereus and Bacillus subtilis, while 1:  - 3: and 14: showed weak antibacterial activity against the gram-negative bacterium Pseudomonas aeruginosa. In addition, compound 1: showed weak antibacterial activity against Escherichia coli.

Styryllactones from Goniothalamus tamirensis.

The phytochemical investigation of the twig and leaf extracts of Goniothalamus tamirensis led to the isolation and identification of 15 compounds including three rare previously undescribed styryllactones, goniotamirenones A-C, together with 12 known compounds. (Z)-6-Styryl-5,6-dihydro-2-pyranone and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one are reported here for the first time as previously undescribed natural products. Their structures were elucidated by spectroscopic methods. Goniotamirenone A was synthesized via a [2 + 2] cycloaddition reaction of 6-styrrylpyran-2-one in quantitative yield. The absolute configurations of goniotamirenones B and C were identified from experimental and calculated ECD data, while the absolute configurations of (-)-5-acetoxygoniothalamin, (-)-isoaltholactone, parvistone E, and 5-(1-hydroxy-3-phenyl-allyl)-dihydro-furan-2-one were identified by single-crystal X-ray diffraction analysis using Cu Kα radiation. The absolute configurations of the other related compounds were determined from comparisons of their ECD spectra with relevant compounds reported in the literature. (-)-5-Acetoxygoniothalamin exhibited potent cytotoxicity against the colon cancer cell line (HCT116) with an IC50 value of 8.6 µM which was better than the standard control (doxorubicin, IC50 = 9.7 µM), while (Z)-6-styryl-5,6-dihydro-2-pyranone was less active with an IC50 value of 22.1 µM.

Bioactive xanthoquinodins and epipolythiodioxopiperazines from Chaetomium globosum 7s-1, an endophytic fungus isolated from Rhapis cochinchinensis (Lour.) Mart.

A new xanthoquinodin B9 (1), together with two known xanthoquinodins, xanthoquinodin A1 (2) and xanthoquinodin A3 (3), three epipolythiodioxopiperazines, chetomin (4), chaetocochin C (5) and dethio-tetra(methylthio)chetomin (6), and four other compounds, chrysophanol (7), emodin (8), alatinone (9), and ergosterol (10) were isolated from the endophytic fungus Chaetomium globosum 7s-1, isolated from Rhapis cochinchinensis (Lour.) Mart. All isolated structures were established based on their spectroscopic data analyses. Compounds 1-6 showed antibacterial activity against Gram positive bacteria with MICs ranging from 0.02 pM to 10.81 µM. Compounds 1-6 also exhibited cytotoxicity against KB, MCF-7 and NCI-H187 cancer cell lines (IC50 0.04-18.40 µM). However, they were cytotoxic towards a normal cell line (Vero cell) with IC50 values ranging from 0.04 to 3.86 µM.

Depsidones and a dihydroxanthenone from the endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261.

Three new compounds including two depsidones (simplicildones J and K) and one dihydroxanthenone (globosuxanthone E) together with nine known compounds were obtained from the crude extracts of two endophytic fungi Simplicillium lanosoniveum (J.F.H. Beyma) Zare & W. Gams PSU-H168 and PSU-H261 which were isolated from the leaves of Hevea brasiliensis. The structures were elucidated by spectroscopic evidence. The absolute configuration of globosuxanthone E was established by means of experimental and calculated TDDFT ECD data. Simplicildone K exhibited antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with equal MIC values of 128 µg/mL. Simplicildone K and globosuxanthone E displayed antifungal activity against Cryptococcus neoformans ATCC90113 with the same MIC values of 32 µg/mL. In addition, known botryohordine C and simplicildone A showed phosphodiesterase 5 inhibitory activity with the IC50 values of 5.69 and 9.96 µM, respectively, and were noncytotoxic toward noncancerous Vero cells.

Bioactive oxaphenalenone dimers from the fungus Talaromyces macrosporus KKU-1NK8.

Six new polyketide-derived oxaphenalenone dimers, talaromycesone C (1) and macrosporusones A-E (2-6), together with eight known analogs, were isolated from the mycelium of the fungus Talaromyces macrosporus KKU-1NK8. Their structures were established based on their spectroscopic data and MS. The absolute configurations of new compounds 1-6 were determined by ECD analyses. Compounds 3 and 8 exhibited antimalarial activity against Plasmodium falciparum. Compound 3 showed activity against NCI-H187 cells, while compound 8 displayed activity against KB, MCF-7 and NCI-H187 cell lines. In addition, compound 11 showed antibacterial activity against Bacillus cereus, Staphylococcus aureus and MRSA.