Biology-oriented Drug Synthesis (BIODS), Structural Characterization and Bioactivities of Novel Albendazole Derivatives

Background: Albendazole is a drug, belongs to the family of benzimidazole, and used as an anthelmintic agent in both human and veterinary medicine. It is marketed as Albenza which is used for the treatment of a variety of parasitic worm infestations such as roundworms, tapeworms, and flukes. In recent past, we have reported various classes of compounds as anti-glycating agents, in continuation of Biology-oriented Drug Synthesis (BIODS), seventeen albendazole derivatives 2-18 were synthesized evaluated for yeast glucose uptake activity. Methods: In the present study, Albendazole (2 g, 7.5 mmol), potassium hydroxide (3 g) were dissolved in ethanol (50 mL) into a 250 mL round-bottomed flask and refluxed for 48 h. TLC (ethyl acetate: hexane, 6:4) was monitored in order to check the reaction progress. After completion, the reaction mixture was dried under air and washed with an excess of distilled water. Precipitates were dried and crystallized from ethanol. The product was characterized by EI-MS and 1H-NMR. Results: Our present study showed that all compounds showed a varying degree of yeast glucose uptake activity ranging between IC50 = 51.41-258.40 μM, compared with standard metronidazole (IC50 = 41.86 ± 0.09 μM). This study has identified a series of potential leads for anti-glycating agents. Conclusion: Biology-oriented drug synthesis and in vitro yeast glucose uptake activity of albendazole derivatives gave rise to a number of lead molecule such as 3 (IC50 = 59.37 ± 0.26 μM), 5 (IC50 = 59.70 ± 0.32 μM), 6 (IC50 = 60.78 ± 0.54 μM), 8 (IC50 = 54.61 ± 0.20 μM), 16 (IC50 = 56.57 ± 0.04 μM) and 14 (IC50 = 51.41 ± 1.25 μM).