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• Synthesis of novel thiosemicarbazones by using furfural and substituted thiosemicarbazide. • Characterization of novel compounds were done through UV–Vis, IR and NMR spectroscopy. • Natural bonding orbital (NBO) properties indicated the stability of compounds. • Frontier molecular orbital energies and MEPs were calculated. • Exploration of NLO properties were performed. A facile condensation reaction between thiosemicarbazide and furfural was accomplished to synthesize thiosemicarbazone derivatives: TMOH, FMOH, TMEH, FMEH, DCFH and DCMH with good yields as 73%, 70%, 72%,71%, 74% and 74%, respectively. They were characterized by spectroscopic techniques as UV–Vis, FT-IR, 1H and 13CNMR. Furthermore, density functional theory (DFT) analysis was performed by applying M06 level with 6–311G(d,p) basis set for geometry optimization, natural bond orbitals (NBOs), linear and nonlinear optical (NLO) and vibrational analyses. Time-dependent DFT applying M06/6–311G(d,p) level of theory was used for computing frontier molecular orbitals (FMOs), molecular electrostatic potential (MEP) and UV–Vis analyses. Experimental values of vibrational wave number and λ max values were seen in good correspondence with the DFT-based results. NBO investigation revealed that title compounds were found with prominent hyper-conjugative interactions having stabilization energies as 57.72, 62.66, 59.95, 58.54, 63.59 and 45.6 kcal/mol , respectively, which are probably the main reasons for their stability. The descending order of E gap was found as DCMH > DCFH > TMOH > TMEH > FMEH > FMOH. Therefore, FMOH , exhibiting the smallest energy gap of 4.416 eV , can be regarded as an efficiently polarized structure, possessing a high capacity for electron transfer. MEP analysis describes the involvement of various reaction sites in chemical reactivity, at different portions of spread electronic cloud over the molecule. The decrease in values of 〈 α〉 for title compounds are found as DCFH > DCMH > FMOH > TMOH > FMEH > TMEH. Moreover, β tot values are found with this order DCFH > DCMH > TMOH > TMEH > FMEH > FMOH. It can be seen that DCMH exhibits a larger NLO response with 〈 α〉 and β tot figured as 300.51 and 2614.07 a.u. , respectively. [ABSTRACT FROM AUTHOR]

• A convenient synthesis of the title compounds. • The most active compounds exhibit strong binding affinity in docking. • AchE inhibition much better than standard. • Ethyl 2-(2-(4-methoxybenzylidene)(benzyl)hydrazinyl)thiazole-4-carboxylate may further tested to be used against Alzheimer disease. A series of N -alkylated and N -benzylated thiazole-4-carboxylates (3a-n) were prepared via alkylation/benzylation of ethyl 2-(2-(arylidene)hydrazinyl)thiazole-4-carboxylates (1). The structures of all synthesized thiazoles were established with FT-IR, 1H-, 13C-NMR and HRMS spectroscopic techniques. All synthesized compounds were screened as inhibitors of acetylcholinesterase (AChE), using galanthamine as the standard. The AChE activity results revealed, that the compounds ethyl 2-(2-(4-methoxybenzylidene)(benzyl)hydrazinyl)thiazole-4-carboxylate (3n) and ethyl 2-(2-(4-methylbenzylidene)(decyl)hydrazinyl)thiazole-4-carboxylate (3k) were moderate inhibitor with IC 50 values 9.56 ± 2.76 and 9.92 ± 0.96 µM, (better than the standard). Simulation studies based on virtual screening of AChE inhibition by molecular docking predicted the binding free energies and molecular inhibition of 3f, 3k and 3n compounds (∆G= - 7.73, ∆G= - 7.91 and ∆G= - 8.13) was comparable with galanthamine. These three compounds occupied the same binding cavity as galanthamine, with greater affinity. Furthermore, in silico, all other compounds also exhibited moderate to good AChE inhibition activities. [Display omitted] [ABSTRACT FROM AUTHOR]