NOVEL 3,4-METHYLENEDIOXYBENZENE DERIVATIVES: SYNTHESIS, CHARACTERIZATION AND EVALUATION FOR THERAPEUTIC ACTIVITY
جامعة النجاح الوطنية
Non-steroidal anti-inflammatory drugs (NSAIDs) are within the most used treatment worldwide; they inhibit the cyclooxygenase enzymes (COX) that mediates the biotransformation of arachidonic acid to inflammatory prostaglandins. In this master thesis, new benzodioxol derivatives with aryl acetate and aryl acetic acid groups were synthesized, identified and evaluated for their potency and selectivity toward COX-1 and COX-2 using an in vitro COX inhibition assay kit. The cytotoxicity for the synthesized compounds were evaluated by using MTS assay against cervical carcinoma cells line (HeLa). All synthesized novel compounds were identify by using FTIR, HRMS, 1H-NMR, and 13C-NMR techniques. The results revealed that the most potent compound against the COX-1 enzyme was 4f with IC50 =0.725 µM. Compound 3b exhibited potent activity against both COX-1 and COX-2 with IC50=1.12 and 1.3 µM, respectively, and its selectivity ratio (0.862) was determined to be better than Ketoprofen (0.196). However, compound 4d was the most selective with a COX-1/COX-2 ratio value of 1.809 in correlation with the Ketoprofen ratio. All compounds exhibited cytotoxic activity against the HeLa Cervical cancer cell line at a high concentration range (0.219– 1.94 mM), and the most cytotoxic compound was 3e with a CC50 value of 219 µM. This was ten fold more than its IC50 values of 2.36 and 2.73 µM against COX-1 and COX-2, respectively. In conclusion, the synthesized library has significant activity against both COX-1 and COX-2 enzymes and ortho halogenated compounds were more potent than the Meta ones.
NSAIDs, COX, Benzodioxol, HeLa, Ketoprofen