Fifteen N4-benzyl-substituted isatin-3-thiosemicarbazones 5a–o were synthesized and evaluated for their urease and glycation inhibitory potential. Lemna aequinocitalis growth and Artemia salina assays were also done to determine their phytotoxic and toxic effects. All compounds are potent inhibitors of the urease enzyme, displaying inhibition [half maximal inhibitory concentration (IC50)=1.08±0.12–11.23±0.19 μm] superior to that of the reference inhibitor thiourea (IC50=22.3±1.12 μm). Compounds 5c, 5d, 5h, 5j,k are potent antiglycating agents, showing glycation inhibitory activity better than that of the reference inhibitor rutin (IC50 values 209.87±0.37–231.70±6.71 vs. 294.5±1.5 μm). In the phytotoxicity assay, 11 thiosemicarbazones 5a–d, 5g, 5h, 5j–l, 5n,o are active, demonstrating 5–100% growth inhibition of L. aequinocitalis at the highest tested concentrations (1000 or 500 μg/mL). In the brine shrimp (A. salina) lethality bioassay, three derivatives 5b, 5j and 5o are active with median lethal dose (LD50) values of 3.63×10−5, 2.90×10−5 and 2.31×10−4 m, respectively.
A series of fifteen N 4 -benzyl substituted 5-chloroisatin-3-thiosemicarbazones 5a-o were synthesized and screened mainly for their antiurease and antiglycation effects. Lemna aequinocitalis growth and Artemia salina assays were carried out to determine their phytotoxicity and cytotoxicity potential. All the compounds proved to be extremely effective urease inhibitors, demonstrating enzyme inhibition much better than the reference inhibitor, thiourea (IC 50 values 1.31 ± 0.06 to 3.24 ± 0.15 vs. 22.3 ± 1.12 μM). On the other hand, eight out of fifteen compounds tested, i.e. 5b, 5c, 5h-k, 5m and 5n were found to be potent glycation inhibitors. Of these, five viz. 5c, 5h-j and 5n proved to be exceedingly efficient, displaying glycation inhibition greater than the reference inhibitor, rutin (IC 50 values 114.51 ± 1.08 to 229.94 ± 3.40 vs. 294.5 ± 1.5 μM).
Key indicators: single-crystal X-ray study; T = 296 K; mean (C-C) = 0.003 Å; R factor = 0.043; wR factor = 0.105; data-to-parameter ratio = 18.9.In the title compound, C 16 H 13 ClN 4 OS, the isatin ring system is oriented at dihedral angles of 10.60 (7) and 72.60 (3) with respect to the thiosemicarbazide and 2-chlorobenzyl groups, respectively. The near planarity of the isatin and thiosemicarbazide groups [r.m.s. deviations of 0.0420 and 0.0163 Å , respectively] is reinforced by intramolecular N-HÁ Á ÁO and N-HÁ Á ÁN hydrogen bonds, which generate S(6) and S(5) rings, respectively. In the crystal, inversion dimers linked by pairs of N-HÁ Á ÁO hydrogen bonds generate R 2 2 (8) loops. Aromatic -stacking interactions between the centroids of heterocyclic five-membered and benzene rings [distance = 3.6866 (11) Å ] are also observed.
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