Coumarin sulfonates: As potential leads for ROS inhibition.

Coumarin sulfonates 4-43 were synthesized by reacting 3-hydroxy coumarin 1, 4-hydroxy coumarin 2and6-hydroxy coumarin 3 with different substituted sulfonyl chlorides and subjected to evaluate for their in vitro immunomodulatory potential. The compounds were investigated for their effect on oxidative burst activity of zymosan stimulated whole blood phagocytes using a luminol enhanced chemiluminescence technique. Ibuprofen was used as standard drug (IC50=54.2±9.2µM). Eleven compounds 6 (IC50=46.60±14.6µM), 8 (IC50=11.50±6.5µM), 15 (IC50=21.40±12.2µM), 19 (IC50=5.75±0.86µM), 22 (IC50=10.27±1.06µM), 23 (IC50=33.09±5.61µM), 24 (IC50=4.93±0.58µM), 25 (IC50=21.96±14.74µM), 29 (IC50=12.47±9.2µM), 35 (IC50=20.20±13.4µM) and 37 (IC50=14.47±5.02µM) out of forty demonstrated their potential suppressive effect on production of reactive oxygen species (ROS) as compared to ibuprofen. All the synthetic derivatives 4-43 were characterized by different available spectroscopic techniques such as 1H NMR, 13C NMR, EIMS and HRMS. CHN analysis was also performed.

Synthesis and ß-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones.

2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their ß-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2µM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16µM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0µM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established.

Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton.

In our effort directed toward the discovery of new anti-diabetic agent for the treatment of diabetes, a library of biscoumarin derivative 1-18 was synthesized and evaluated for α-glucosidase inhibitory potential. All eighteen (18) compounds displayed assorted α-glucosidase activity with IC50 values 16.5-385.9 µM, if compared with the standard acarbose (IC50 = 906 ± 6.387 µM). In addition, molecular docking studies were carried out to explore the binding interactions of biscoumarin derivatives with the enzyme. This study has identified a new class of potent α-glucosidase inhibitors.

ß-glucuronidase inhibitory studies on coumarin derivatives.

Twenty-three (23) derivatives of coumarin (5-27) were synthesized and screened for their in vitro ß- glucuronidase (E. coli) inhibitory activities. Only three compounds, 7,8-dihydroxy-4-methyl-2H-chromen-2-one (9) (IC50 = 52.39 ± 1.85 µM), 3-chloro-6-hexyl-7-hydroxy-4-methyl-2H-chromen-2-one (18) (IC50 = 60.50 ± 0.87 µM), and 3,6- dichloro-7-hydroxy-4-methyl-2H-chromen-2-one (15) (IC50 = 380.26 ± 0.92 µM) displayed activities against ß- glucuronidase as compared to standard D-saccharic acid 1,4-lactone (IC50 = 45.75 ± 2.16 µM). The results indicated that the activity of the synthetic coumarins depends upon the substituents present on the coumarin skeleton.