Functionalized Pyrazole: Synthesis, DFT Calculation, Molecular Docking Studies, and Insecticidal Evaluation of Some New Pyrazole Derivatives Against the Cotton Leafworm, <i>Spodoptera littoralis</i> (Boisd.)

One of the main forces motivating the creation of innovative insecticidal active agents is the exponential rise in resistance to traditional chemical pesticides. Examining new classes of insecticidal compounds with distinct modes of action is one way to meet this problem. Thus, novel pyrazole derivatives 1-6 have been synthesized via a one-pot, three-component reaction of cyanoguanidine with various aldehydes and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one in the presence of sodium methoxide as a catalyst. Under laboratory circumstances, all synthesized compounds were tested as insecticidal agents due to their chemical structures having the active center of phenylpyrazole insecticides. Bioassay experiments were carried out against the second and fourth larvae of Spodoptera littoralis. When compared to other synthetic target compounds, [4-(4-chlorophenyl)-3-methyl-1-phenyl-1,4,5,7-tetra-hydro-6H-pyrazolo[3,4-d]pyrimidin-6-ylidene] cyanamide 2 showed good insecticidal activity, with 0.553 mg/L for second instar larvae and LC₅₀ values of 1.28 mg/L for fourth instar larvae. DFT optimization of the synthesized compounds using the B3LYP/6-311G revealed their electronic properties, highlighting key factors such as HOMO, LUMO energies, and the energy gap, which are crucial in predicting chemical reactivity and biological potential. Molecular docking studies against the 6HUP protein further confirmed compound 5's superior binding affinity, suggesting its strong inhibitory effect on ion channels, potentially making it a powerful insecticidal agent.