A new series of thiosemicarbazone derivatives (1–11) were prepared from various aldehydes and isocyanates with high yields and practical methods. The structures of these compounds were elucidated by Fourier transform infrared, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR spectroscopic methods and elemental analysis. Cytotoxic effects of target compounds were determined by 2,3‐bis‐(2‐methoxy‐4‐nitro‐5‐sulfophenyl)‐2H‐tetrazolium‐5‐carboxanilide assay and compound 1 showed significant cytotoxic activity against both MCF‐7 and MDA‐MB‐231 cells, with half‐maximal inhibitory concentration values of 2.97 μM and 6.57 μM, respectively. Moreover, in this study, the anticholinergic and antidiabetic potentials of these compounds were investigated. To this aim, the effect of the newly synthesized thiosemicarbazone derivatives on the activities of acetylcholinesterase (AChE) and αglycosidase (α‐Gly) was evaluated spectrophotometrically. The title compounds demonstrated high inhibitory activities compared to standard inhibitors with Ki values in the range of 122.15–333.61 nM for α‐Gly (Ki value for standard inhibitor = 75.48 nM), 1.93–12.36 nM for AChE (Ki value for standard inhibitor = 17.45 nM). Antiproliferative activity and enzyme inhibition at the molecular level were performed molecular docking studies for thiosemicarbazone derivatives. 1M17, 5FI2, and 4EY6, 4J5T target proteins with protein data bank identification with (1–11) compounds were docked for anticancer and enzyme inhibition, respectively.

A series of substituted quinolines was screened for their antiproliferative, cytotoxic, antibacterial activities, DNA/protein binding affinity, and anticholinergic properties by using the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide cell proliferation, lactate dehydrogenase cytotoxicity, and microdilution assays, the Wolfe–Shimmer equality method, the Ellman method, and the esterase assay, respectively. The results of the cytotoxic and anticancer activities of the compounds displayed that 6‐bromotetrahydroquinoline (2), 6,8‐dibromotetrahydroquinoline (3), 8‐bromo‐6‐cyanoquinoline (10), 5‐bromo‐6,8‐dimethoxyquinoline (12), the novel N‐nitrated 6,8‐dimethoxyquinoline (13), and 5,7‐dibromo‐8‐hydroxyquinoline (17) showed a significant antiproliferative potency against the A549, HeLa, HT29, Hep3B, and MCF7 cancer cell lines (IC50 = 2–50 μg/ml) and low cytotoxicity (∼7–35%) as the controls, 5‐fluorouracil and cisplatin. The compound–DNA linkages are hyperchromic or hypochromic, causing variations in their spectra. This situation shows that they can be bound to DNA with the groove‐binding mode, with Kb value in the range of 2.0 × 103–2.2 × 105 M–1. Studies on human Gram(+) and Gram(−) pathogenic bacteria showed that the substituted quinolines exhibited selective antimicrobial activities with MIC values of 62.50–250 μg/ml. All tested quinoline derivatives were found to be effective inhibitors of acetylcholinesterase (AChE) and the human carbonic anhydrase I and II isoforms (hCA I and II), with Ki values of 46.04–956.82 nM for hCA I, 54.95–976.93 nM for hCA II, and 5.51–155.22 nM for AChE. As a result, the preliminary data showed that substituted quinolines displayed effective pharmacological features. Molecular docking studies were performed to investigate the binding modes and interaction energies for compounds 2–17 with AChE (PDB ID: 4EY6), hCA I (PDB ID: 1BMZ), and hCA II (PDB ID: 2ABE).

In this study, preparation, as well as investigation of α-glycosidase and cholinesterase (ChE) enzyme inhibition activities of furan-2-ylmethoxy-substituted compounds 1-7, are reported. Peripherally, tetra-substituted copper and manganese phthalocyanines (5 and 6) were synthesized for the first time. The substitution of furan-2-ylmethoxy groups provides remarkable solubility to the complex and redshift of the phthalocyanines Q-band. Besides, the inhibitory effects of these compounds on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and α-glycosidase (α-Gly) enzymes have been investigated. The AChE was inhibited by these compounds (1-7) in low micromolar levels, and K i values were recorded between 11.17 ± 1.03 and 83.28 ± 11.08 µM. Against the BChE, the compounds demonstrated K i values from 7.55 ± 0.98 to 81.35 ± 12.80 µM. Also, these compounds (1-7) effectively inhibited α-glycosidase, with K i values in the range of 744.87 ± 67.33 to 1094.38 ± 88.91 µM. For α-glycosidase, the most effective K i values of phthalocyanines 3 and 6 were with K i values of 744.87 ± 67.33 and 880.36 ± 56.77 µM, respectively. Moreover, the studied metal complexes were docked with target proteins PDB ID: 4PQE, 1P0I, and 3WY1. Pharmacokinetic parameters and secondary chemical interactions that play an active role in interaction were predicted with docking simulation results. Overall, furan-2-ylmethoxysubstituted phthalocyanines can be considered as potential agents for the treatment of Alzheimer's diseases and diabetes mellitus.

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