Synthesis,Characterization And Theoretical Analysis Of (E)-1-(Substituted Benzylidene)-4-(3-Methyl,5-Fluorophenyl) Thiosemicarbazone Derivatives

Thiosemicarbazone derivatives with specific tridentate coordination structures and multiple binding sites are an important class of compounds.Its biological activity is attributed to the carbonyl group of the parent.The carbonyl group in thiosemicarbazone is often chelated with metal ions and easily cross-linked with polypeptide compounds.Thiosemicarbazone compounds and their metal complexes have various pharmacological activities,such as Antibacterial,antitumor,antiviral,antifungal,antituberculous activity,inhibition of tyrosinase,etc.Meanwhile,the complexation with transition metals and the introduction of halogenated substituents on the benzene ring usually enhance their pharmacological activities.However,there are few reports on halogen-substituted thiosemicarbazides in the literature.In this paper,fifteen unreported(E)-1-(substituted benzylidene)-4-(3-methyl,5-fluorophenyl)thiosemicarbazide derivatives(PhRMFT)were synthesized by one-pot method,FT-IR,NMR and X-ray single crystal diffraction were used to test its molecular structure,and its biological activity was further analyzed by theoretical and experimental methods.In this paper,taking compounds 3-PhMeMFT(compound 5)and 3-PhClMFT(compound 6)as examples,based on density functional theory,the B3LYP/6-31+G(d,p)basis set was used to optimize the molecular geometry,and The resulting optimal structure will serve as the starting point for subsequent quantization calculations.The theoretical values of bond length and bond angle of the compound were compared with the actual values,and the molecular frontier orbitals were compared with their ultraviolet spectra to analyze the influence of different substituents on the peak position,so as to link the different substituents with biological activity.By introducing Hirshfeld surface analysis and molecular electrostatic potential map analysis,topology analysis,IGM and RDG analysis,Fukui function analysis,and NBO analysis,the intermolecular and intramolecular interactions and electron distribution characteristics were studied.The antibacterial activity provides a theoretical basis.In order to elucidate the effect of different substituent types and different substitution sites of the benzene ring on the biological activity,in this paper,the antibacterial and antioxidant activities of 15 PhRMFT derivatives were determined by disc diffusion method and DPPH scavenging method.It found that compounds 4-PhFMFT(compound 11)and 4-PhTriFMeMFT4-PhFMFT(compound 15)had outstanding bacteriostatic effect on target phytopathogens compared with standard marketed drugs,and it was also found that in the para position of the benzene ring and the introduction of halogen atoms would reduce the Improve its antibacterial activity,and DPPH scavenging experiments show that compound 4-PhMeMFT(compound 9)has obvious antioxidant effect.In addition,molecular docking technology was used to simulate the binding mode of ligand compounds and receptor large proteins,so as to screen potential antibacterial drugs.Finally,the drug-like and pharmacokinetic properties of the compounds are simulated by the technology of computer software-assisted drug design,thus laying a foundation for the subsequent design of new drugs.