Polycyclic Aromatic Compounds最新文献

1-Piperoylpiperidine (1-PIP) was crystallized as a single unit by a slow evaporation process, and it was examined using XRD and FT-IR spectroscopy. The centrosymmetric monoclinic structure is confirmed by XRD. The functional groups were determined by experimental FT-IR range from 4000 to 400 cm⁻¹. Density functional theory was used to do calculations on quantum chemistry on B3LYP/6-311++G (d,p) theory. The vibrational wavenumbers were calculated, and experimentally obtained were assigned and compared. The molecule’s reactivity and kinetic stability are revealed via molecular orbital research. The Mulliken atomic charge distribution and molecular electrostatic potential analyses provide additional evidence of the molecule’s reactive site. The electronic spectrum was computed through TD-DFT and the electronic transition was attained at π→π*. The molecule’s bioactivity is shown by the natural bond orbital analysis. The efficiency and contribution of interactions between various atoms were evaluated using the Hirshfeld analysis. The DPPH assay was performed to access the antioxidant ability of 1-PIP. The disk diffusion test exhibited the antibacterial efficiency of 1-PIP molecule. The safety profile of 1-PIP was confirmed through physiochemical and pharmacokinetic predictions. In silico docking evaluation was performed for 1-PIP against 10 breast cancer-aided proteins and the higher binding affinity was recorded for NAMPT, which was further investigated through molecular dynamic (MD) simulation. MD simulation for a time period of 50 ns confirmed the stability of 1-PIP bounded NAMPT structure.

Amide compounds exhibit tautomerism which is an important property in organic synthesis. Evidence for the occurrence of tautomeric forms for amido-imidols is interpreted via mass spectrometry techniques. The tautomeric equilibrium of pyrimidone moiety was rationalized and the existence of amido-imidol tautomerism in 6-methyl-4-(3-nitro-phenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic acid ethyl ester (6M3NP) was verified. The proton nuclear magnetic resonance splitting pattern shows the intramolecular hydrogen bonding between the keto-enol forms which evidences through a fluctuation in the integration value of C4 proton. Synthesis proceeds through novel BF₃-OEt₂ catalysed one-pot, simple, efficient, minimal catalyst usage, compatible, outstanding yield, and rapid protocol for the Tetrahydropyrimidinones via Biginelli reaction is described. The titled compound 6M3NP was characterized by infrared and nuclear magnetic resonance. The compound was screened for antimicrobial activity against 3 microbes which showed a high zone of inhibition when compared to standard streptomycin. The antioxidant activity using 2,2-diphenyl-1-picryl-hydrazyl-hydrate assay gave a promising IC₅₀ value of 14.11 µM. The more the radical scavenging activity the greater the chance of functioning as an anticancer agent. 6M3NP was tested against breast cancer cells after scrutiny with 60 cell lines. Clonogenicity and soft agar colony formation were significantly reduced in MCF7, MDA-MB-231, and T47D breast cancer cells after treatment with 6M3NP. The in-silico dock score obtained for the title compound was 62.845 which is 40% more than the standard drug Nifedipine. In-vitro cell line analysis results showed that the title compound possesses maximum activity than commercial drug Nifedipine against cardiovascular disease as a calcium channel blocker.

The synthesis of novel 5-(2-((1(E/Z),2E)-1,3-disubstitutedallylidene)hydrazinyl)-1,3-dimethyl-4-nitro-1H-pyrazole (4a–k) was attempted via reaction involves a nucleophilic attack which takes place at the carbonyl group of the α,β-unsaturated carbonyls. The transformation proceeds via an effective addition-elimination reaction in the presence of catalytic amount of concentrated H₂SO₄. The cytotoxicity of synthesized compounds was evaluated against two tumor cell lines, MCF-7 and MDA-MB-231, via MTT assay. The compounds 4a–d showed better toxicity than tamoxifen on MCF-7 cells, ranging from 26.28 to 12.96 µM with 4b having the lowest IC₅₀ among the compounds tested. On the other hand, the compounds have moderate toxicity on MDA-MB-231 with 4c showing the lowest IC₅₀. The docking study suggests that these Schiff bases chalcone scaffolds might facilitate the further development of investigated compounds as anticancer agents.

Based on the tremendous pharmacological activities of compounds containing thiazole and carboxamide moieties, the current study aims to prepare new series of thiazole, pyrazole, pyridine, and thiophene derivatives incorporating thiazole carboxamide moiety. Construction of the target compounds was achieved via different chemical transformations and using easily accessible starting materials. The structures of the synthesized compounds were confirmed by all possible spectral and elemental analyses. Results from the in-silico studies showed different Lipophilicity (log p) and Number of Lipinsk’s violations due to the presence of NH₂, C≡N, OH, and C=O groups which make more electrostatic hydrogen bond interactions in compounds 17 and 20 which increase their TPSA (Å2). These results were confirmed through docking simulation with PDBID: 5I9I which showed the least binding affinity with different proteins, and optimization of these heterocyclic compounds with computational calculations and identification of their physical descriptors which showed more stabilities and directed us for biological evaluation for further studies.

Piperidine is an essential moiety of morphine, responsible for the analgesic activity. Among number of other analgesic targets, µ-opioid receptor is still the most focused and therapeutically important in the management of pain. In this study, a series of novel derivatives of 4 amino methyl piperidine were synthesized and explored for analgesic potential against mu opioid receptor. Their structures were elucidated by FT-IR, 1H NMR, and LC-MS followed by in vivo analgesic evaluation by tail-flick method and writhing test. Among all derivatives, HN58 showed excellent analgesic activity (100% inhibition) in writhing test. Furthermore, reduction of HN58 analgesic effect by naloxone suggests its involvement with µ-OR. Molecular docking approach was also utilized to compare the analgesic potential of synthesized derivatives in order to find potent µ-OR inhibitors, we designed five piperidine derivatives with analgesic activity. We have elucidated the binding affinities and binding modes of these piperidine derivatives including standard molecules Morphine, Fentanyl Pethidine and DAMGO revealed a well-known µ-O inhibitor (having binding affinity ranges from −8.13 to −13.37 kcal/mol). All novel derivatives exhibited the remarkable binding score and encapsulated in the binding pocket of transmembraneous helices engaged by the residues Q124, W133, I144, D147, Y148, M151, V236, I296, H297, W318, I322, and Y236. All derivatives revealed excellent binding scores and interaction mechanism as compared to morphine, pethidine, and fentanyl respectively.

Considering the unprecedented attributes governed by metal-organic framework nanostructures, the present report discloses the fabrication of [Zn₂(H₂N-BDC)₂(4-bpdh)]·3DMF as a Zn-based MOF catalyst (TMU-16-NH₂ (TMU = Tarbiat Modares University)) through the coordination of 2,5-bis(4-pyridyl)-3,4-diaza-2,4-hexadiene (4-bpdh) ligand to the Zn(NO₃)₂·6H₂O salt under hydrothermal approach. In order to certify the successful synthesis of the catalyst, FT-IR, XRD, TGA, Elemental microanalysis, ICP OES and BET measurements were employed. The developed TMU-16-NH₂ catalytic agent acts as a promising candidate to deliver a new class of pharmaceutically relevant 2,4-diphenylpyrido[4,3-d]pyrimidine scaffolds via the Michael addition annulations of benzimidamid hydrochloride to (3E,5E)-3,5-bis-(benzylidene)-4-piperidone reacting species. The devised methodology is accompanied with noteworthy benefits including mild reaction conditions, wide substrate scope, excellent product yields and short reaction span. Besides, facile retrievability and remarkable reusability of the catalyst for 5 successive runs without any appreciable loss in catalytic efficacy are the additional factors that rationalize this protocol as worthwhile. Our findings highlight the potential of using MOFs as efficient and versatile catalysts in organic synthesis and contribute to the growing body of literature on the synthesis of pyrido[4,3-d]pyrimidines with diverse biological activities.

For the performing this research multicomponent reaction of isatin, electron-deficient acetylenic compounds, α-haloketones, ammonium acetate, isothiocyanates and methyl aziridine in aqueous at room temperature was investigated for the production of novel derivatives of azepinothiazine in excellent yields. The synthesized azepinothiazines have OH, NH₂ and NH functional groups that have acidic hydrogen and show high antioxidant activity. These synthesized compounds also displayed antimicrobial activity by using the disk diffusion procedure and two Gram-positive and Gram-negative bacteria. Also, to better understanding reaction mechanism density functional theory-based quantum chemical methods have been applied. The employed process for the production of azepinothiazine has some benefits such as short time of reactions, excellent efficiency of the product, easy separation of products.

In this study, synthesis, characterization, optical, and in silico medicinal properties of a Schiff base compound, 4-((4,5-difluoro-2-hydroxybenzylidene)amino)-1,5-dimethyl-2-phenyl-2,3-dihydro-1H-pyrazol-3-ol, were reported. X-ray, FTIR, and UV-vis spectra, including computational and experimental data, were used to characterize the Schiff base molecule. Pharmacophore analysis of the molecular structure was performed to investigate the active interaction centers that can interact with macromolecular biological targets. Since the synthesized Schiff base is not centrosymmetric, the NLO material potential was evaluated using the DFT approach, and it showed higher NLO efficacy compared to the reference molecule urea. Potential biological targets of the title compound were investigated using a web server (LigTMap). Top twelve candidate targets, including transferase, hydrolase, and kinase targets, were identified. According to the docking scores, the most potent target of the title compound was determined as vascular endothelial growth factor receptor 2 (PDB: 3VO3).

Coronavirus disease-19 (COVID-19), a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related sickness that has already claimed millions of lives throughout the world, is one of the most contagious illnesses in known human history. At this time, neither vaccines nor effective medicines exist that can effectively cure COVID-19 patients or stop the virus from spreading. Even though the creation of drugs and vaccines may take a while, scientific communities all over the world have reacted rapidly and have been working ceaselessly on them. In light of this uncertainty, repurposing currently existing antiviral drugs may be the best line of action to speed the creation of effective SARS-CoV-2 therapeutics. Updated information is also required on potential pharmacological targets, therapeutic and vaccine development, and results. In this study, we propose topological descriptors and status distance-based polynomials for many COVID-19 antiviral drugs. The quantitative structure–property relationship (QSPR) connection of the proposed topological indices (TIs) is also investigated. Curve fitting models are obtained and looked at for the physico-chemical properties of the COVID-19 drugs in line with the specified indices. Our models and results may contribute to the identification of innovative therapeutics for the treatment of COVID-19.

A novel series of imidazole appended quinoline derivatives (6a–j) have been synthesized using the one-pot three-component reaction that occurred between the starting materials of substituted 2-phenoxyquinolin-3-carbaldehydes (3a-j), benzil (4), and ammonium acetate (5) by taking equimolar ratio. The newly synthesized imidazole-appended quinolines were subjected to probable inhibition against the anti-diabetic drug target maltase enzyme. The efficacy was tested using in-silico molecular docking analysis and molecular dynamics simulation. The studies revealed that the test 6f ligand (3-(4,5-diphenyl-1H-imidazol-2-yl)-2-phenoxy quinoline) is a strong inhibitor of the target protein maltase when compared with the known inhibitor acarbose and sheds new light on the medicinal chemistry research for the application of the synthesized 6f ligand in the pharmaceutical industry.