A novel coumarin-triazole-thiophene hybrid: synthesis, characterization, ADMET prediction, molecular docking and molecular dynamics studies with a series of SARS-CoV-2 proteins

Abstract

Synthesis, characterization and theoretical studies of a novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4 H -1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2 H -chromen-2-one ( 1 ), which was fabricated from 4-ethyl-5-(thiophen-2-yl)-4 H -1,2,4-triazole-3-thiol and 4-(chloromethyl)-6,7-dimethyl-2 H -chromen-2-one, are reported. The resulting compound was characterized by microanalysis, IR, 1 H, and 13 C APT NMR spectroscopy. The DFT calculations examined the structure and electronic properties of 1 in gas phase. Its reactivity descriptors and molecular electrostatic potential revealed the reactivity and the reactive centers of 1 . ADMET properties of 1 were evaluated using the respective online tools. It was established that 1 exhibit positive gastrointestinal absorption properties and negative human blood-brain barrier penetration. The Toxicity Model Report revealed that 1 belongs to toxicity class 4. Molecular docking was additionally applied to study the interaction of 1 with some SARS-CoV-2 proteins. It was established that the title compound is active against all the applied proteins with the most efficient interaction with Papain-like protease (PLpro). The interaction of 1 with the applied proteins was also studied using molecular dynamics simulations. Graphical abstract A novel coumarin-triazole-thiophene hybrid 4-(((4-ethyl-5-(thiophen-2-yl)-4H-1,2,4-triazol-3-yl)thio)methyl)-6,7-dimethyl-2H-chromen-2-one ( 1 ) is reported. The structure and electronic properties of 1 were examined by the DFT calculations. ADMET properties of 1 were also evaluated. Molecular docking and molecular dynamics simulations were applied to study interactions of 1 with a series of the SARS-CoV-2 proteins. Supplementary Information The online version contains supplementary material available at 10.1007/s12039-022-02127-0.

New 2H‐Chromene‐Based Hydrazone Derivatives as Promising Anti‐Breast Cancer Agents: Efficient Synthesis, Spectral Characterization, Molecular Docking, and ADMET Studies

“…To assess oral bioavailability, a radar chart was designed to depict six physiochemical parameters, namely lipophilicity (LIPO), size (SIZE), polarity (POLAR), solubility (INSOLU), saturation (INSATU), and flexibility (FLEX). As seen in figure 10, most of the six physiochemical chemical characteristics of the two potent compounds ( 10 r and 12 b ) under investigation are within the permissible range (pink region) [70,71] …”

“…As seen in figure 10, most of the six physiochemical chemical characteristics of the two potent compounds (10 r and 12 b) under investigation are within the permissible range (pink region). [70,71] The Lipinski's, Ghose's, and Veber's parameter results of tested compounds 10 r, 12 b, and a standard drug (Doxorubicin) are presented in table 7. According to "Lipinski's Rule of five (RO5)" a compound may be considered an orally active drug if it would not violate more than one of five guidelines: Molecular Weight (MW) should be � 500 g/mol, octanol-water partition coefficient (cLog P) should be � 5, Number of hydrogen bond acceptors (H-ba) should be � 10, number of hydrogen bond donors (H-bd) should be � 5 and tropological polar surface area (tPSA) should be � 150 Å 2 .…”

Recent Trends in the Synthesis and Bioactivity of Coumarin, Coumarin–Chalcone, and Coumarin–Triazole Molecular Hybrids

“…In 2023, Omar et al synthesized a novel coumarin–triazole hybrid by reacting 4-ethyl-5-(thiophen-2-yl)-4 H -1,2,4-triazole-3-thiol 190 with an equimolar amount of 4-(chloromethyl)-6,7-dimethyl-2 H -chromen-2-one 191 to give coumarin–triazole 192 in 75% yield ( Scheme 43 ) [ 110 ].…”

Quantum chemical calculation employed for investigation mesitylene compound

“…Mesitylene has been proposed as a useful ingredient in the development of simple hydrocarbon mixtures that quantitatively mimic the gas-phase combustion behavior of real liquid transportation fuels as a model or surrogate fuel. To aid in its implementation, a novel chemical kinetic model for the combustion of mesitylene was developed after its numerous combustion characteristics were characterized experimentally [12]. The experimentally determined laminar burning velocities, shock ignition delays, and oxidative reactivity profiles of a high-pressure flow reactor are provided [13,14].…”