Design, Synthesis, Antiviral Evaluation, and Molecular Dynamics Simulation Studies of New Spirocyclic Thiopyrimidinones as Anti HCoV-229E.

The current pandemic threat presented by viral pathogens like SARS-CoV-2 (COVID-19) suggests that virus emergence and dissemination are not geographically confined. As a result, the quest for antiviral agents has become critical to control this pandemic. In the current study, we provide a novel family of spirocyclic thiopyrimidinone derivatives whose cytotoxicity and antiviral efficacy were investigated against human coronavirus 229E (HCoV-229E) as a model for the Coronaviridae family. We utilized MTT and cytopathic effect (CPE) inhibitory tests on green monkey kidney (vero-E6) cell lines. The new molecules showed varied degrees of antiviral activity against the vero-E6 cell lines with minimal cytotoxicity. With a high level of a selective index (SI=14.8), compound 9 showed outstanding inhibitory ability and could effectively suppress the human coronavirus 229E. Molecular dynamics simulation (MD) studies were performed to measure the interaction and stability of the protein-ligand complex in motion. The MD results for the most active compound 9 explored remarkable interactions with the binding pockets of the main protease (Mpro) of SARS-CoV-2 enzyme confirming the results gained from in vitro experiments. ADMET properties were also predicted for all the tested compounds. All these results demonstrated that the novel spirocyclic thiopyrimidinone derivatives would have the potential to be safe, low-cost chemical compounds that might be used as a novel therapeutic option for Coronaviridae viruses like COVID-19.

Development of Antimicrobial Laser-Induced Photodynamic Therapy Based on Ethylcellulose/Chitosan Nanocomposite with 5,10,15,20-Tetrakis(m-Hydroxyphenyl)porphyrin.

The development of new antimicrobial strategies that act more efficiently than traditional antibiotics is becoming a necessity to combat multidrug-resistant pathogens. Here we report the efficacy of laser-light-irradiated 5,10,15,20-tetrakis(m-hydroxyphenyl)porphyrin (mTHPP) loaded onto an ethylcellulose (EC)/chitosan (Chs) nanocomposite in eradicating multi-drug resistant Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans. Surface loading of the ethylcelllose/chitosan composite with mTHPP was carried out and the resulting nanocomposite was fully characterized. The results indicate that the prepared nanocomposite incorporates mTHPP inside, and that the composite acquired an overall positive charge. The incorporation of mTHPP into the nanocomposite enhanced the photo- and thermal stability. Different laser wavelengths (458; 476; 488; 515; 635 nm), powers (5-70 mW), and exposure times (15-45 min) were investigated in the antimicrobial photodynamic therapy (aPDT) experiments, with the best inhibition observed using 635 nm with the mTHPP EC/Chs nanocomposite for C. albicans (59 ± 0.21%), P. aeruginosa (71.7 ± 1.72%), and S. aureus (74.2 ± 1.26%) with illumination of only 15 min. Utilization of higher doses (70 mW) for longer periods achieved more eradication of microbial growth.

Preparation of new polycyclic compounds derived from benzofurans and furochromones. An approach to novel 1,2,3-thia-, and selena-diazolofurochromones of anticipated antitumor activities.

Base catalyzed condensation of enaminoketones (3a,b) with malononitrile yields the respective 7-imino-5[2(substituted)prop-1-enyl]furochromene-6-carbonitriles (4a-d) according to the nature of base used. Compounds (3a, b) condense also with indan-1,3-diketone (5) to give α, ß-unsaturated carbonyl compounds (6a) and (6b), respectively. Pyrrolidine-catalyzed condensation of visnaginone (2a) and khellinone (2b) with active methylenes yields the corresponding 1-[7,7-(substituted) furobenzodihydropyrone derivatives (7a-e) which condense with semicarbazide to give the respective semicarbazones (8a-e). Compounds (8b,e) react with thionyl chloride to give the respective 1,2,3-thiadiazoles (9a,b) meanwhile compounds (8a-e) react also with selenium dioxide to give 1,2,3-selenadiazoles (9c-g), respectively. Chalcones (11a,b) were obtained upon condensing (2a,b) with ferrocene-2-carboxaldehyde (10). Compatible elementary and spectroscopic measurements were in good accord with the structures postulated for the new compounds. The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of four (breast: MCF-7, cervix: HELA, colon: HCT116 and liver: HEPG2) human solid tumor cell lines and the structure activity relationship (SAR) was discussed.