Design, synthesis and biological evaluation of novel benzodioxole derivatives as COX inhibitors and cytotoxic agents
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(2020) 14:54 Hawash et al. BMC Chemistry https://doi.org/10.1186/s13065-020-00706-1
Open Access
RESEARCH ARTICLE
Design, synthesis and biological evaluation of novel benzodioxole derivatives as COX inhibitors and cytotoxic agents Mohammed Hawash1* , Nidal Jaradat1 , Saba Hameedi1 and Ahmed Mousa2
Abstract Non-steroidal anti-inflammatory drugs are among the most used drugs. They are competitive inhibitors of cyclooxygenase (COX). Twelve novel compounds (aryl acetate and aryl acetic acid groups) were synthesized in this work in order to identify which one was the most potent and which group was most selective towards COX1 and COX2 by using an in vitro COX inhibition assay kit. The cytotoxicity was evaluated for these compounds utilizing MTS assay against cervical carcinoma cells line (HeLa). The synthesized compounds were identified using FTIR, HRMS, 1H-NMR, and 13C-NMR techniques. The results showed that the most potent compound against the COX1 enzyme was 4f with IC50 = 0.725 µM. The compound 3b showed potent activity against both COX1 and COX2 with IC50 = 1.12 and 1.3 µM, respectively, and its selectivity ratio (0.862) was found to be better than Ketoprofen (0.196). In contrast, compound 4d was the most selective with a COX1/COX2 ratio value of 1.809 in comparison with the Ketoprofen ratio. All compounds showed cytotoxic activity against the HeLa Cervical cancer cell line at a higher concentration ranges (0.219– 1.94 mM), and the most cytotoxic compound was 3e with a CC50 value of 219 µM. This was tenfold more than its IC50 values of 2.36 and 2.73 µM against COX1 and COX2, respectively. In general, the synthesized library has moderate activity against both enzymes (i.e., COX1 and COX2) and ortho halogenated compounds were more potent than the meta ones. Keywords: Benzodioxole, COX, Ketoprofen Introduction Some of the most used analgesics are non-steroidal antiinflammatory drugs (NSAIDs) that target the cyclooxygenase (COX) enzymes. NSAIDs are used for various therapeutic purposes globally. Due to their wide pharmacological effects, including analgesic, anti-inflammatory and antipyretic effects, they are investigated as being some of the best choices for treating different diseases like arthritis and rheumatism, and they are widely used as analgesics. Actually, acetyl salicylic acid (ASA), one of the members of this family, has been used for more than *Correspondence: [email protected] 1 Department of Pharmacy, Faculty of Medicine and Health Sciences, AnNajah National University, P.O. Box 7, Nablus 00970, Palestine Full list of author information is available at the end of the article
a 100 years [1, 2]. The biosynthesis of prostaglandin H2 from arachidonic acid is catalysed by COX enzymes [3]. Prostaglandin H2 is the main component in the formation of other prostaglandins, such as thromboxane and prostacyclin, which play important roles in different biological responses [4, 5]. In fact, COX1 and COX2 are the two major isoforms of COX membrane-bound enzymes [6]. COX1 is involved in the biosynthesis o
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