Synthesis, <i>In Vitro</i> Biological Screening, and <i>In Silico</i> Computational Studies of Some Novel Imidazole‐2‐thiol Derivatives

Darji

et al. 2020

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In the present study, a novel series of N‐((substituted)carbamothioyl)‐2,4‐dimethylquinoline‐3‐carboxamide (7a‐7s) was synthesized by microwave‐assisted method. Structure of these derivatives was examined by spectroscopic techniques such as 1H NMR, 13C NMR, FT‐IR, and ESI‐MS. Further, the novel synthesized compounds were evaluated for their in‐vitro biological activities against antibacterial, antifungal, antimalarial, and antituberculosis activity as well as for in‐silico study. The antimalarial results demonstrated that compounds 7c and 7q (0.02 μg/mL) have notable potency against Plasmodium falciparum compared with chloroquine (0.02 μg/mL); compounds 7l (0.10 μg/mL), 7e, 7s (0.19 μg/mL), 7b, 7p (0.15 μg/mL), 7a, 7f, and 7f (0.25 μg/mL) also exhibited good activity against P. falciparum compared with quinine (0.26 μg/mL) as standard drug. Docking was performed on PFDHFR‐TS, given the effect of compounds against the P. falciparum strain was excellent in comparison with standard drug. Molecular docking suggested that compounds 7b, 7i and 7c, 7e, and 7l closely bind with the active site of protein 3JSU and 4DP3, respectively, and compared with biological activity. We have also carried out molecular dynamics simulation on the best dock compound 7e complex with PDB: 3JSU to check the stability of docked complex and their molecular interaction. The calculated ADME‐Tox descriptors for the synthesized compounds validated good pharmacokinetics properties, suggesting that these compounds could be used as hit for the development of the new active agents.

Section: Computational Studymentioning

confidence: 99%

Section: Computational Studymentioning

confidence: 99%

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Synthesis of novel quinoline‐thiosemicarbazide hybrids and evaluation of their biological activities, molecular docking, molecular dynamics, pharmacophore model studies, and ADME‐Tox properties

Darji

et al. 2020

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“…A set of ADME‐Tox‐related properties of the synthesized compounds were predicted by using a Qikpro program (Schrödinger, LLC, New York, NY, 2018). [ 69 ] LigPrep module was used to prepare the compounds and utilized for the calculation of pharmacokinetic parameters by Qikpro module. The program Qikpro generates physically relevant descriptors and uses them to perform ADME‐Tox predictions and utilizes the method of Jorgensen to calculate pharmacokinetic properties and descriptors.…”

Section: Computational Studymentioning

confidence: 99%

“…MD simulations have been accompanied by Desmond program [ 70 ] as implemented Schrödinger Materials Science Suite 2015‐4. [ 69 ] OPLS_2005 force field with NPT ensemble class have been utilized, while pressure and temperature were set to 1.0325 bar and 300 K, respectively. The system was modeled by placing one 7 s molecule into the cubic box with around 3000 water molecules, and the simulation time was set to 10 ns, cut‐off radius was set to 12 Å, pressure was set to 1.0325 bars, and the temperature was set to 300 K. In all cases when Desmond was used, input and output files were manipulated by Maestro graphical user interface application of Schrödinger Materials Science Suite 2018.…”

Section: Computational Studymentioning

confidence: 99%

Microwave assisted synthesis, biological activities, and in silico investigation of some benzimidazole derivatives

Bhavsar

Acharya

Jethava

et al. 2020

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Some derivatives of 2-substituted benzimidazole were prepared via coupling of N-methyl-o-phenylenediamine or o-phenylenediamine with different aromatic aldehydes catalyzed by Ni(OAc) 2 in the presence of chloroform under microwave-assisted conditions. Structural confirmation of all synthesized molecules was investigated by FT-IR, 13 C NMR, 1 H NMR, ESI-MS, and Elemental analysis. All prepared molecules were examined for in-vitro pharmaceutical activities like antibacterial, antifungal, antimalarial, antituberculosis, and antioxidant. Additionally, in silico study was also carried out. We also evaluated the steadiness and molecular interaction of docked complex, that is, complex of molecule (7s) with PDB: 5ZNI and complex of derivative (7l) with PDB: 3VLN, we have established a molecular dynamics model on the best dock molecules. All newly prepared molecules were authenticated to have excellent pharmacokinetics stuffs via calculated ADME-Tox descriptors, which signifying that these derivatives could be utilized as hit for the expansion of the some innovative active compounds.

Design, synthesis, and biological evaluations of (E)‐2‐(1‐[2‐mercapto‐4‐methyl‐1‐phenyl‐1H‐imidazol‐5‐yl]ethylidene)hydrazinecarbothioamide derivatives as antimicrobial agents

Daraji

Rajani²,

Jayanthi

et al. 2021

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In recent year, the development of new drugs as antibacterial agents is an important resolution to overcome drug‐resistant pathogens. Imidazole derivatives were synthesized using the microwave irradiation method and were characterized using spectral analysis techniques such as proton nuclear magnetic resonance, mass, and Fourier transform infrared spectroscopy. All the analogous were assessed for their in vitro antimicrobial activity and in silico; minimum inhibition concentration values of some conjugates were evaluated against extended spectrum beta‐lactamases, vancomycin‐resistant enterococci, and Methicillin‐resistant Staphylococcus aureus strains from clinical samples. All the analogous were used as ligands in molecular docking and adsorption, distribution, metabolism, and excretion against saDHPS. Furthermore, compounds were also examined for their in vitro antituberculosis and antimalarial activity.