A Comprehensive In Silico Study of New Metabolites from Heteroxenia fuscescens with SARS-CoV-2 Inhibitory Activity

Chemical investigation of the total extract of the Egyptian soft coral Heteroxenia fuscescens, led to the isolation of eight compounds, including two new metabolites, sesquiterpene fusceterpene A (1) and a sterol fuscesterol A (4), along with six known compounds. The structures of 1–8 were elucidated via intensive studies of their 1D, 2D-NMR, and HR-MS analyses, as well as a comparison of their spectral data with those mentioned in the literature. Subsequent comprehensive in-silico-based investigations against almost all viral proteins, including those of the new variants, e.g., Omicron, revealed the most probable target for these isolated compounds, which was found to be M^pro. Additionally, the dynamic modes of interaction of the putatively active compounds were highlighted, depending on 50-ns-long MDS. In conclusion, the structural information provided in the current investigation highlights the antiviral potential of H. fuscescens metabolites with 3β,5α,6β-trihydroxy steroids with different nuclei against SARS-CoV-2, including newly widespread variants.     

Novel synthesis of thieno[2,3‐b]pyridine and substituted 2‐thienylthiourea derivatives as antibiotic agents

Derivatives of thieno[2,3‐b]pyridine, 2‐thienylthiourea, 2‐thienylurea, 2‐thienylacetamide incorporating the 2‐phthalimidomethyl moiety have been synthesized. The synthesized compounds were then investigated for antibacterial activity against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. The compounds were also investigated for antifungal activity against Aspergillus niger and Fusarium oxysporium. The structures of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

Facile synthesis of 2-(substituted amino)-4<Emphasis Type="Italic">H</Emphasis>-thieno[3,2-<Emphasis Type="Italic">e</Emphasis>]-1,3-thiazin-4-ones

Interaction between 2,5-dichlorothiophene-3-carbonyl isothiocyanate, accessible via 2,5-dichlorothiophene-3-carbonyl chloride, and model heterocyclic amines produced the respective 2,5-dichloro-N-(substituted aminocarbonothioyl)thiophene-3-carboxamides. Upon heating, the deprotonated form of the latter underwent intramolecular cyclization to deliver the corresponding 2-(substituted amino)-4H-thieno[3,2-e]-1,3-thiazin-4-ones. The structures of these new bicyclic derivatives and their acyclic precursors are based on microanalytical and spectral (IR, MS, and NMR) data. Correspondence: Rajab Abu-El-Halawa, Chemistry Department, Faculty of Science, Al al-Bayt University, Mafraq, Jordan.     

Intrachain electron and energy transfer in conjugated organometallic oligomers and polymers

The synthesis of polymers of the type (-Cz-C[triple chemical bond]C-PtL(2)-C[triple chemical bond]C-Cz-X-)(n) along with the corresponding model compounds (Ph-PtL'(2)-C[triple chemical bond]C-Cz)(2)-X-, where Cz=3,3'-carbazole, X=nothing, Cz, or F (2,2'-fluorene), L=PBu(3), and L'=PEt(3) are reported. The electronic spectra (absorption, excitation, emission, and ns-transient spectra) and the photophysics of these species in 2-methyltetrahyrofuran (2MeTHF) at 298 and 77 K are presented. Evidence for singlet electron and triplet energy transfer from the Cz chromophore to the F moiety are provided and discussed in detail. The rate for electron transfer is very fast (>4 x 10(11) s(-1)), whereas that for triplet-triplet energy transfer is much slower (approximately 10(3) s(-1)). This work represents a very rare example of studies that address electronic communication in the backbone of a conjugated organometallic polymer.     

Probing the electronic communication of the isocyanide bridge through the luminescence properties of the d9-d9 [ClPt(mu-dppm)2Pt(C triple bond N-PCP)]+ and A-Frame [ClPd(mu-dppm)2(mu-C=N-PCP)PdCl] complexes

The homodinuclear d9-d9 ClM(mu-dppm)2MCl2 complexes, 1 (M ) Pt) and 2 (M ) Pd) react with the conjugated and luminescent PCP-NC ligand (3, PCP ) [2.2]paracyclophane) to provide the corresponding d9-d9 terminal[ClPt(mu-dppm)2Pt(CNsPCP)]Cl (4) and d8-d8 A-frame [ClPd(mu-dppm)2(mu-CdNsPCP)PdCl] (5) isocyanide complexes, respectively. These two bimetallic complexes were characterized by IR, 1H, and 31P{1H} NMR and bychemical analysis. IR data (nu(CN) bridging vs terminal) reveal a terminal isocyanide bonding mode for 4 (2147cm(-1)) and an A-frame structure for 5 (1616 cm(-1)). The optical and emission properties of the free isocyanide 3as well as those of the homodinuclear complexes 4 and 5 were studied by UV-visible and luminescence spectroscopy and by photophysical measurements. The unexpected presence of simultaneous intraligand pipi* fluorescence and phosphorescence attributable to the organic PCP-NC ligand, as well as luminescence from the inorganic M2-bonded Pt2(mu-dppm)2 center arising from a lower energy excited LMCT state (ligand-to-metal-charge-transfer) for4 at 77 K, indicates a weak conjugation between the two chromophores and an absence of efficient singlet andtriplet energy transfers. For 5, only the fluorescence and phosphorescence bands of the PCP-NC ligand are observed [since the A-frame XPd(mu-dppm)2(mu-L)PdX (L ) isocyanide, X ) halide) is not luminescent], stressing that the NtC bridge exhibits modest electronic communication properties.     

Studies with S‐alkylpyrimidine: New route for the synthesis derivatives of isoxazol,pyrazolo[1,5‐a]pyrimidine,pyridazine, pyridine,thieno[2,3‐b]pyridine and thiophene of potential anti‐HIV

Derivatives of thiophene, thieno[2,3‐b]pyridine, pyridine, isoxazol, pyrazolo[1,5‐a]pyridine, pyridazine linked with s‐pyrimidine derivative have been synthesized and tested for antimicrobial and antifungal activities. The structure of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

Conventional and microwave irradiation assisted synthesis of new 1,2,4‐triazepine‐3‐thiones

New 1,2,4‐triazepine‐3‐thiones have been obtained during the respective reactions of N‐substituted‐hydrazino carbothioamides with dimethyl acetylenedicarboxylate and dibenzoyl acetylene under prolonged reflux in acetic acid and/or DMF. However, the reaction of the starting materials in DMF under microwave irradiation afforded the same products in higher yields within a few minutes.     

UV partial least-squares calibration and liquid chromatographic methods for direct quantitation of levofloxacin in urine

Levofloxacin was determined in human urine samples by application of a spectrophotometric multivariate calibration partial least-squares (PLS-1) method. A calibration set consisting of standards was prepared by using a multilevel multifactor experimental design. In order to ensure accurate results, the calibration matrix included a urine sample free of levofloxacin (i.e., urine blank). The components of the calibration matrix were levofloxacin and urine. The concentration of levofloxacin ranged from 0.5 to 16.5 microg/mL. Different urine concentrations were used as the second component of the calibration matrix in order to include the information inherent in the changes in the UV spectrum for urine upon dilution. In addition, a high-performance liquid chromatographic method was proposed. In this method, a Shim-pack amino column was used at ambient temperature with a mobile phase of 25 mM potassium dihydrogen phosphate (pH adjusted to 3.1 with phosphoric acid)-acetonitrile (70 + 30, v/v), and the flow rate was 1 mL/min. UV detection at 293 nm was used for quantitation. The proposed methods were applied to the determination of the dissolution rate for tablets containing levofloxacin. The urinary excretion pattern for the cumulative amount of levoflacin excreted was also calculated.     

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti‐Inflammatory Agents

The synthesis of a novel and attractive class of nonsteroidal anti‐inflammatory and antimicrobial organoiron dendrimers attached to the well‐known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram‐positive and Gram‐negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin‐resistant Staphylococcus aureus, vancomycin‐resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti‐inflammatory activities of these dendrimers are evaluated. The results of in vivo anti‐inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti‐inflammatory activity; however, second‐generation dendrimer ( G2‐D6 ) shows the best anti‐inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2‐D6  is the safest drug on biological tissues.     

New Disulfiram Derivatives as MAGL-Selective Inhibitors

Monoacylglycerol lipase (MAGL) is a key enzyme in the human endocannabinoid system. It is also the main enzyme responsible for the conversion of 2-arachidonoyl glycerol (2-AG) to arachidonic acid (AA), a precursor of prostaglandin synthesis. The inhibition of MAGL activity would be beneficial for the treatment of a wide range of diseases, such as inflammation, neurodegeneration, metabolic disorders and cancer. Here, the author reports the pharmacological evaluation of new disulfiram derivatives as potent inhibitors of MAGL. These analogues displayed high inhibition selectivity over fatty acid amide hydrolase (FAAH), another endocannabinoid-hydrolyzing enzyme. In particular, compound 2i inhibited MAGL in the low micromolar range. However, it did not show any inhibitory activity against FAAH.