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1.
ACS Appl Nano Mater ; 4(11): 11881-11887, 2021 Nov 26.
Article in English | MEDLINE | ID: mdl-37556290

ABSTRACT

The rapid transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-driven infection signifies an ultimate challenge to global health, and the development of effective strategies for preventing and/or mitigating its effects are of the utmost importance. In the current study, an in-depth investigation for the understanding of the SARS-CoV-2 inactivation route using graphene oxide (GO) is presented. We focus on the antiviral effect of GO nanosheets on three SARS-CoV-2 strains: Wuhan, B.1.1.7 (U.K. variant), and P.1 (Brazilian variant). Plaque assay and real-time reverse transcription-polymerase chain reaction (RT-PCR) showed that 50 and 98% of the virus in a supernatant could be cleared following incubation with GO (100 µg/mL) for 1 and 60 min, respectively. Transmission electron microscopy (TEM) analysis and protein (spike (S) and nucleocapsid (N) proteins) decomposition evaluation confirm a two-step virus inactivation mechanism that includes (i) adsorption of the positively charged spike of SARS-CoV-2 on the negatively charged GO surface and (ii) neutralization/inactivation of the SARS-CoV-2 on the surface of GO through decomposition of the viral protein. As the interaction of S protein with human angiotensin-converting enzyme 2 (ACE2) is required for SARS-CoV-2 to enter into human cells, the damage to the S protein using GO makes it a potential candidate for use in contributing to the inhibition of the worldwide spread of SARS-CoV-2. Specifically, our findings provide the potential for the construction of an effective anti-SARS-CoV-2 face mask using a GO nanosheet, which could contribute greatly to preventing the spread of the virus. In addition, as the effect of surface contamination can be severe in the spreading of SARS-CoV-2, the development of efficient anti-SARS-CoV-2 protective surfaces/coatings based on GO nanosheets could play a significant role in controlling the spread of the virus through the utilization of GO-based nonwoven cloths, filters, and so on.

2.
Bioorg Chem ; 105: 104387, 2020 12.
Article in English | MEDLINE | ID: mdl-33130344

ABSTRACT

7H-Benzo[7,8]chromeno[2,3-d]pyrimidin-9(8H)-amine (6a,b) have been synthesized via hydrazinolysis of the imidates (5a,b). Polysubstituted chromenotriazolopyrimidine (7a-j), (12a,b) and Schiff base (8a,b) derivatives have also been prepared. The new heterocyclic derivatives were affirmed by spectral data. The target compounds have been screened for antibacterial and antifungal activity. Compounds 6a,b and 7a-c, g,h displayed the most favorable antimicrobial activities in resemblance to the reference antimicrobial agents by IZ range over 24 mm. In addition, MIC, MBC and MFC were also tested and screen for most active compound 6a by 6.25 µg/mL showing bactericidal effect. SAR study revealed that the antimicrobial vitality of the target compounds was safely influenced by the lipophilicity substituents and the calculated log P value. The potent compounds were subjected into in vitro enzyme screening (14α-Demethylase and DNA Gyrase) against both interesting targets and showed good inhibitory profile. Molecular modeling analyses were introduced and discussed focusing on the docking of active compounds into two essential targets, and their ADMET properties were studied.


Subject(s)
14-alpha Demethylase Inhibitors/pharmacology , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Benzopyrans/pharmacology , Topoisomerase II Inhibitors/pharmacology , 14-alpha Demethylase Inhibitors/chemical synthesis , 14-alpha Demethylase Inhibitors/chemistry , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Aspergillus/drug effects , Benzopyrans/chemical synthesis , Benzopyrans/chemistry , Candida albicans/drug effects , DNA Gyrase/metabolism , Dose-Response Relationship, Drug , Gram-Positive Bacteria/drug effects , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Sterol 14-Demethylase/metabolism , Structure-Activity Relationship , Topoisomerase II Inhibitors/chemical synthesis , Topoisomerase II Inhibitors/chemistry
3.
Bioorg Chem ; 98: 103725, 2020 05.
Article in English | MEDLINE | ID: mdl-32199303

ABSTRACT

A series of heterocyclic compounds with a sulfonamide moiety were synthesized from reaction of enaminone 4 with active methylene compounds, glycine derivatives, 1,4-benzoquinone, hydroxylamine hydrochloride, hydrazonyl halides and dimethylacetylenedicarboxylate. The newly synthesized sulfonamide derivatives were characterized by FT-IR, 1H NMR, 13C NMR, mass spectroscopy, elemental analysis and alternative synthetic routes. The reactions products were evaluated for their antiproliferative activity against a panel of three different human cancerous cell lines, MCF-7 (breast), HepG-2 (liver) and HCT-116 (colon) and the results were deployed to derive the structure-activity relationships (SAR). Various test compounds were potent antiproliferative to cancerous cells; reaching very low micromolar levels, as in case of 21 which showed IC50 value of 6.2 µM against HepG-2 cell. In addition, treatment of cancerous cells with the synthesized compounds induced cell apoptosis and G2/M phase arrest evidenced by flow cytometric analysis. Furthermore, the activity of the synthesized compounds against TOP I and II were documented by DNA relaxation assays. Data revealed that compound 24 significantly interfered with TOP I- and II-mediated DNA relaxation, nicking and decatenation, with IC50 values 27.8 and 33.6 µM, respectively. Moreover, the molecular docking studies supported the results from enzymatic assays, where compound 24 was intercalated between nucleotides flanking the DNA cleavage site via pi-pi stacking and hydrophobic interactions. In conclusion, aromatic heterocycles linked to sulfonamides are excellent molecular frameworks amenable for optimization as dual TOP I and II poisons to control various human malignancies.


Subject(s)
Antineoplastic Agents/pharmacology , DNA Topoisomerases, Type II/metabolism , DNA Topoisomerases, Type I/metabolism , Heterocyclic Compounds/pharmacology , Molecular Docking Simulation , Sulfonamides/pharmacology , Topoisomerase Inhibitors/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Heterocyclic Compounds/chemistry , Humans , Molecular Structure , Structure-Activity Relationship , Sulfonamides/chemistry , Topoisomerase Inhibitors/chemical synthesis , Topoisomerase Inhibitors/chemistry , Tumor Cells, Cultured
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