Synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives and exploring molecular and cytotoxic properties based on DFT and molecular docking studies

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

“…Very recently, 1,4-dihydropyrano[2,3- c ]pyrazole derivatives 124 were obtained in excellent yields through a piperidine-catalyzed four-component reaction of β -ketoesters 8 , malononitrile 2 , aryl/heteroaryl aldehydes 1 , and hydrazine hydrate 4 in ethanol under microwave heating at 140 °C for 2 min ( Scheme 14 ) [ 112 ]. After completion of the reaction, the product was filtered, washed with methanol, and recrystallized from ethanol.…”

“…In addition, the compounds 124a (R = Me, R 1 = 4-fluorophenyl) and 124e (R = Me, R 1 = 4-(piperidin-1-yl)phenyl) showed better cytotoxicity against SKOV-3 and A549 cell lines with IC 50 values of 2.0 and 1.1 μM, respectively. Molecular docking studies were performed for all synthesized compounds against His-tag human thymidylate synthase (HT-hTS) in a complex with 2′-deoxyuridine 5′-monophosphate (dUMP) (PDB: 6QXH) [ 112 ]. The compounds 124a (R = Me, R 1 = 4-fluorophenyl), 124b (R = C 6 H 5 , R 1 = 4-fluorophenyl), and 124f (R = C 6 H 5 , R 1 = 4-(piperidin-1-yl)phenyl) stabilized in a TS binding pocket similar to dUMP through an arrangement of the pyranopyrazole cluster in perpendicular mode with Tyr270 via a hydrogen bond interaction, while the compounds 124c (R = Me, R 1 = 4-(1 H -pyrrol-1-yl)phenyl) and 124d (R = C 6 H 5 , R 1 = 4-(1 H -pyrrol-1-yl)phenyl) occupied the binding pocket by interaction with Asn238.…”

Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

“…The final pose was chosen according to the lowest Δ G and lowest RMSD, while the binding-efficiency (BE) was selected from the highest Δ G . The inhibition-constant ( K i ) was generated for 6–19 hybrids to promote validation of the BE, and should be in the range of 0.1–1.0 μM, ideally lower than 10 nM, 47 where a lower K i value indicates a higher BE efficiency for the molecules. All the calculated parameters for the compounds ( 6–19 ) and 5-FU against TS are tabulated in Table 5.…”

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

“…The other tested compounds showed lower interaction energy than the reference erlotinib. All compounds showed a normal range of bioactivity parameters Ki, LE, and FQ [ 41 ].…”