Structure modification of mefenamic acid and evaluate their bioactivities

Abstract

Thousands of years medicine and natural products have been closely linked through the use of traditional medicines and natural poisons (Phillipson et al., 2001). Lately, pharmaceutical industries

mainly pay their attention on natural products and their bioactivities to develop novel drugs which shows promising activities on diseases in humans as well as in plants. Since biological assays are used to detect the biological activity on synthetic compounds and natural products. There are several kinds of bioassays such as, antioxidant, antifungal, phytotoxicity, cytotoxicity and enzyme inhibitory activities (e.g. lipase, α-amylase, α-Glucosidase etc). Though there are several types of bioassays, most pharmaceutical manufacturing industries limited their research activities only towards one or few types of bioassays. There can be hidden bioactivities which are important in medicinally, agriculturally and environmentally. Therefore it is important to study about the other bioactivities too by doing the structure modifications of existing drugs and evaluate their bioactivities using various types of bioassays. By doing the modification of the exiting drug that can be enhanced the efficiency of the drug usage.

Mefenamic acid (MFA) which is used as a pain killer from many years ago. It is a Non-Steroidal Anti-

Inflammatory Drug (NSAID) which exhibits poor water solubility properties (Dixit et al., 2012). MFA

is a prescription medicine used for the relief of mild to moderate pain, including painful menstrual

periods (Asl et al., 2008). There can be some hidden important bioactivities which were not studied yet in addition as a pain-killer. The aim of this study was to improve the usages of the drug for industrially, agriculturally and environmentally. Therefore the drug was synthetically modified by acetylation/acylation reaction methods.

Methodology

Pure MFA was separated from the tablet by using column chromatography technique. Separated pure MFA was subjected to acetylation and acylation reactions according to Arnold et al., 2007. Acylation

was carried out with acid chlorides such as acetyl chloride (AC), benzoyl chloride (BC) and crotonoyl chloride (CC), while acetylation with acetic anhydride. Efficiency of the drug and its synthetic

derivatives were tested by subjecting to bioassays such as α-amylase inhibition assay (Giancarlo et al., 2006), antioxidant assay (DPPH radical scavenging assay) (Mensor et al., 2001), phytotoxicty (bio-assay with lettuce seed germination) (Drewes et al., 1995) and cytotoxicity (brine shrimp

lethality assay) assay using Artemia salina (Subbaraju et al., 2005).

The Inhibition percentage was plotted against the sample concentration and the fitted line plot was established. Then IC50value (Inhibitory Concentration) was calculated in order to the 50% inhibition.