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Title: Synthesis Characterization and Biological Evaluation of Ibuprofen and Mefenamic acid Derivatives
Authors: Daud, Saima
Keywords: Physical Sciences
Issue Date: 2022
Publisher: Hazara University, Mansehra
Abstract: Derivatization of already established pharmacologically active drug molecules is an interesting strategy fascinated the minds of organic scientists over the years. This line of action coincides with the idea of multi-target, multi-role drug development. This thesis described the synthesis, characterization and biological evaluation of ibuprofen (IBP) and mefenamic acid (MEFA) derivatives. Both IBP and MEFA belongs to the class of drugs known as nonsteroidal anti-inflammatory drug (NSAID). In the present work, the derivatization of IBP and MEFA is divided into three different schemes. In first scheme, five membered heterocyclic derivatives were synthesized by following different steps. Initially, IBP and MEFA acid 208(a,b) were converted into their methyl esters 209(a,b) followed by the formation of respective hydrazide 210(a,b) by treatment with hydrazine hydrate. The hydrazide on treatment with different aryl substituted isothiocynates gave thiosemicarbazide derivatives 211(a-l). The thiosemicarbazide undergoes intramolecular cyclization upon treatment with NaOH, Hg(OAc)2, and conc. H2SO4 to form 1,2,4-triazole 212(a-l), 1,3,4-oxadiazole 214(a-l) and 1,3,4-thiadiazole 215(a-l) respectively. The selected 1,2,4-triazole derivatives were further modified at their SH group by alkyl halide to form alkylated 1,2,4-triazole derivatives 213(a-h). The synthesis of these azole containing heterocyclic compounds were confirmed through physical data and spectroscopic techniques. These derivatives were also evaluated for enzyme inhibition activities like 15-Lipoxygenase (15-LOX) inhibition, cell viability, urease inhibition, and α-glucosidase inhibition activities. These synthesized derivatives showed significant inhibitory potential against urease and α-glucosidase inhibition while weak inhibitory potential against 15-LOX enzyme. In the second scheme, the 1,3,4-oxadiazole based Schiff base derivatives of IBP and MEFA were synthesized by following three different steps. In the first step 1,3,4-oxadiazole derivatives 216(a,b) of respective drugs were synthesized by treatment of their hydrazides with carbon disulphide in the presence of KOH, which then form acylated intermediate 218(a-j) upon reaction with substituted phenacyl bromides. xxvi These acylated intermediates on reaction with different aromatic amines gives their Schiff base derivatives 219(a-o), 220(a-o). The synthesis of these compounds were also confirmed through both physical data and the spectroscopic data. Some of these derivatives exhibited promising inhibitory potency for all the three enzymes i.e., Jack bean urease, α-glucosidase and soybean 15-LOX and are also found least toxic. In the last scheme, Isatin based Schiff base derivatives of IBP and MEFA were prepared. First alkylated isatin intermediate 222(a-f) were synthesized which on treatment with drug hydrazides 210(a,b) gives Schiff base derivatives 223(a-r). The structures of these derivatives were also confirmed by spectroscopic techniques like 1H NMR, 13C NMR and mass analysis. In this series of compounds, all the compounds showed remarkable inhibitory potential against urease and α-glucosidase while low inhibitory potential against 15-LOX.
Gov't Doc #: 26934
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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