Global trials are
grappling toward identifying prosperous remediation
against the ever-emerging and re-emerging pathogenic respiratory viruses.
Battling coronavirus, as a model respiratory virus, via repurposing
existing therapeutic agents could be a welcome move. Motivated by
its well-demonstrated curative use in herpes simplex and influenza
viruses, utilization of the nanoscale zinc oxide (ZnO) would be an
auspicious approach. In this direction, ZnO nanoparticles (NPs) were
fabricated herein and relevant aspects related to the formulation
such as optimization, structure, purity, and morphology were elucidated.
In silico molecular docking was conducted to speculate the possible
interaction between ZnO NPs and COVID-19 targets including the ACE2
receptor, COVID-19 RNA-dependent RNA polymerase, and main protease.
The cellular internalization of ZnO NPs using human lung fibroblast
cells was also assessed. Optimized hexagonal and spherical ZnO nanostructures
of a crystallite size of 11.50 ± 0.71 nm and positive charge
were attained. The pure and characteristic hexagonal wurtzite
P
63
mc
crystal structure was also observed.
Interestingly, felicitous binding of ZnO NPs with the three tested
COVID-19 targets, via hydrogen bond formation, was detected. Furthermore,
an enhanced dose-dependent cellular uptake was demonstrated. The obtained
results infer a rationale, awaiting validation from further biological
and therapeutic studies.
Up to date, there were no approved drugs against coronavirus (COVID-19) disease that dangerously affects global health and the economy. Repurposing the existing drugs would be a promising approach for COVID-19 management. The antidepressant drugs, selective serotonin reuptake inhibitors (SSRIs) class, have antiviral, anti-inflammatory, and anticoagulant effects, which makes them auspicious drugs for COVID 19 treatment. Therefore, this study aimed to predict the possible therapeutic activity of SSRIs against COVID-19. Firstly, molecular docking studies were performed to hypothesize the possible interaction of SSRIs to the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-COV-2) main protease. Secondly, the candidate drug was loaded in lipid polymer hybrid (LPH) nanoparticles to enhance its activity. The studied SSRIs were Fluoxetine hydrochloride (FH), Atomoxteine, Paroxetine, Nisoxteine, Repoxteine RR, and Repoxteine SS. Interestingly, FH could effectively bind with SARS-COV-2 main protease via hydrogen bond formation with low binding energy (-6.7 kcal/mol). Moreover, the optimization of FH-LPH formulation achieved 65.1±2.7% encapsulation efficiency, 10.3±0.4% loading efficiency, 98.5±3.5 nm particle size, and -10.5±0.45 mV zeta potential. Additionally, it improved cellular internalization in a time-dependent manner with good biocompatibility on Human lung fibroblast (CCD-19Lu) cells. Therefore, the study suggested the potential activity of FH-LPH nanoparticles against the COVID-19 pandemic.
Background:
There is a great need to discover more drugs with antimycobacterial activities to fight lung cancer
and tuberculosis (two of the deadliest diseases world-wide). To our knowledge, the present study is the first to report
antimycobacterial activity of imidazole-fused heterocycles.
Objective:
Construction of some bis-imidazole fused heterocycles with potential anti-tubercular and/or potent antitumor
activities.
Method:
A series of bis-imidazole fused derivatives 6-8 and 13-16 was constructed using bis-phenacyl bromide derivative 2
as a synthetic platform. Compound 2 was also used to access bis-quinoxaline 20, bis-benzothiazine derivatives 23, and bisthiazolopyrimidine derivatives 26. The new bis-imidazole derivatives were evaluated for their anticancer activity against
lung carcinoma cell line (A-549) using Cisplatin as a reference drug. The new compounds were also screened for their antitubercular activity against M. tuberculosis (ATCC 25177) using Isoniazid as a reference drug.
Result:
Among the new bis-imidazole derivatives, three examples showed remarkable antitumor activities while five other
compounds showed high antimycobacterial activity.
Conclusion:
A novel series of bis-imidazole fused heterocycles was developed. Multiple prototypes of this new series
showed remarkable anti-tubercular and/or potent antitumor activities.
Objective
The aim of this study was to synthesize ten 1,4-dihydropyridine (DHP) derivatives in which substituted cyclohexane rings were fused to the DHP ring and to determine how different ester groups and the benzoyl substituent introduced in 4-phenyl ring affected their calcium channel blocking activity.
Methods
A microwave-assisted one-pot method was applied for the synthesis of compound 1–5 according to a modified Hantzsch reaction. The benzoyl moiety was introduced in the 4-phenyl ring of these dihydropyridines by refluxing with benzoyl chloride in acetone in the presence of anhydrous potassium carbonate. Synthesized products were characterized by elemental analysis, IR, 1H-NMR and 13C-NMR spectroscopy. The inhibitory actions of compounds 1–10 on calcium channel blocking activity were tested on isolated rat aorta preparations.
Results
The obtained pharmacological results showed that although all compounds are potent relaxing agents on isolated rat aorta smooth muscle, introduction of a benzoyloxy substitiuent on the phenyl ring (compound 6–10) decreased the relaxant effect of these compunds.
Conclusion
The reported 1,4-DHP derivatives have calcium channel blocking activity on rat aorta smooth muscle.
In the title compound, C21H19BrN2O2·C2H6OS, the indole ring system is essentially planar, with a maximum deviation of 0.050 (3) Å for the non-bridgehead C atom adjacent to the N atom. The two cyclohex-2-enone rings adopt half-chair conformations. An intramolecular C—H⋯O hydrogen bond occurs. The solvent molecule exhibits minor disorder of the S atom [site occupancies = 0.8153 (16) and 0.1847 (18)]. In the crystal, molecules are linked by N—H⋯O hydrogen bonds, forming layers parallel to the bc plane.
This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to aff ect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profi le of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photoproduct. Pharmacological tests on the molecules showed a good muscle relaxing eff ect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.
In the present study a microwave-assisted one-pot method was applied for the synthesis of 18 novel condensed 1,4-dihydropyridines carrying the indole moiety. The compounds were achieved by the reaction of appropriate 1,3-cyclohexanedione, substituted indole carboxaldehyde derivative, alkyl acetoacetate and ammonium acetate in methanol, according to a modified Hantzsch reaction. The structure elucidation of the compounds was carried out by spectral methods including X-ray studies. Their spasmolytic activities through calcium channel blockade were assayed on isolated rat ileum. The obtained results indicated that the introduction of the brom atom on the indole ring altered the mentioned activity positively.
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