Cu~(II)-Tyrosinase Enzyme Catalyst-Mediated Synthesis of 2-Thioxopyrimidine Derivatives with Potential Mosquito Larvicidal Activity: Spectroscopic and Computational Investigation as well as Molecular Docking Interaction with OBPs of Culex quinquefasciatus

摘要

A series of 2-thioxo pyrimidine derivatives 1, (1a-1e) and 2, (2a-2e) were synthesized via Biginelli reaction by using Cu~(II)-tyrosinase (Cu~(II)-Tyr) as an enzyme catalyst in up to 80-92% yield. The compounds 1, (1a-1e) and 2, (2a-2e) were characterized by IR, 1HNMR, ~(13)CNMR, mass spectra and elemental analyses. The synthesized compounds 1, (1a-1e) and 2, (2a-2e) were screened for mosquito larvicidal activity against Culex quinquefasciatus. The compound 2a was 80% mortality at 100 μg/mL with the LD50 value of 55.94 μg/mL than the control Permethrin 60.03 μg/mL respectively. Molecular docking studies of synthesized compounds were carried out and the results proposed that the compound 2a as a potential candidate to mosquito odorant-binding protein 3OGN inhibitors. In addition, computational studies, the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energies showed that the charge transfer occurs in the inside of the molecule and also gives the chemical reactivity descriptors, and molecular electrostatic potential (MESP) is also calculated. Therefore, experimental and theoretical studies were well supported for the compound 2a as a potential larvicide activity aganist mosquito larvae of Culex quinquefasciatus.