SYNTHESIS OF PIPERIDINIUM-3,3'-(ARYLMETHYLENE)BIS-LAWSONE DERIVATIVES AS ?-GLUCOSIDASE INHIBITORS

• Main Author: Taufik, Muhammad
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/86653
• Institution: Institut Teknologi Bandung

Lawsone (2-hydroxy-1,4-naphthoquinone) is a secondary metabolite derived from the plant Lawsonia inermis, commonly known as "henna" or "pacar kuku" in local terminology. This plant is reported to exhibit various biological activities, including antioxidant, antibacterial, antifungal, cytotoxic properties, and ?-glucosidase inhibition. ?-Glucosidase inhibitors play a crucial role in the management of type 2 diabetes by inhibiting enzymes involved in carbohydrate digestion, thereby reducing monosaccharide absorption and lowering postprandial blood glucose levels. Although lawsone shows potential as an ?-glucosidase inhibitor, its low solubility and limited bioavailability present significant challenges for therapeutic development. The formation of salt derivatives is one of the strategies that can be employed to enhance the solubility and bioavailability of lawson. Among the lawsone derivatives that have been synthesized are triethylammonium bis-lawsone salts, which exhibit ?-glucosidase inhibitory activity, and piperidinium bis-lawsone salts, whose biological activity has yet to be investigated. This study aims to synthesize and characterize derivatives of lawsone in the form of piperidinium salts, specifically piperidinium-3,3'-(aryl-methylene)bis-lawsone, which are expected to enhance its solubility and biological potential as an ?-glucosidase inhibitor. Ten lawsone derivatives were successfully synthesized, including piperidinium 3,3' (phenylmethylene)bis(2-hydroxy-1,4-naphthoquinone) (1), piperidinium 3,3'-((4 hydroxyphenyl)methylene)bis(2-hydroxy-1,4-naphthoquinone) (2), piperidinium 3,3'-((4-diethylaminophenyl)methylene)bis(2-hydroxy-1,4-naphthoquinone) (3), piperidinium 3,3'-((4-methoxyphenyl)methylene)bis(2-hydroxy-1,4 naphthoquinone) (4), piperidinium 3,3'-((4-hydroxy-3 methoxyphenyl)methylene)bis(2-hydroxy-1,4-naphthoquinone) (5), piperidinium 3,3'-((3,4-dimethoxyphenyl)methylene)bis(2-hydroxy-1,4-naphthoquinone) piperidinium (6), 3,3'-((3,4,5-trimethoxyphenyl)methylene)bis(2-hydroxy-1,4 naphthoquinone) (7), piperidinium 3,3'-((4-nitrophenyl)methylene)bis(2-hydroxy 1,4-naphthoquinone) (8), piperidinium 3,3'-((4-bromophenyl)methylene)bis(2 hydroxy-1,4-naphthoquinone) (9), and ethyl-2,4-dimethyl-5-((1,3,4-trioxo-3,4 dihydro-2H-naphthalene-2-ylidene)methyl)-1H-pyrrole-3-carboxylate (10). The synthesis was performed via a one-pot reaction, and the molecular structures were determined using 1D NMR (¹H, ¹³C), 2D NMR (HSQC, HMBC), and Mass sepctrometry. Biological activity assays against the ?-glucosidase enzyme were conducted for all synthesized compounds. The results demonstrated significant inhibitory activity for compounds 2, 3, 4, 8, 9, and 10, with IC50 values of 6.29 µM, 2.40 µM, 16.85 µM, 3.32 µM, 0.55 µM, and 2.26 µM, respectively. These IC50 values indicate that these compounds hold strong potential as promising candidates for the development of type 2 diabetes therapies.