INTRODUCTION Sulfonamides are a very important class of compounds in the pharmaceutical industry, being widely used as anticancer, antiinflammatory and antiviral agents 1 . They are well known for their antimicrobial activity because of their being less- expensive, less toxic and having superb inhibitory effect against bacterial infections 2 . Nucleophilic substitution reactions occur during sulfonamide synthesis. Amine acts as nucleophile, attacks on sulfonyl chloride 3 . Sulfonamides are effective inhibitors of carbonic anhydrase 4 and are wide spectrum anti- biotics. More than 30 drugs bearing this functionality have been reported to apparent clinical applications 5 . These comp- ounds are most effective inhibitor against HIV protease. These also take account of anticonvulsants, diuretics, hypoglycemic functionality. Sulfonamides also find their wide use in case of animal husbandry and food additives 6 . Acetylcholinesterase (AChE, EC 3.1.1.7) and buty- rylcholinesterase (BChE, EC 3.1.1.8) consist of a family of Synthesis, Spectral Characterization and Biological Screening of N-Substituted Derivatives of N-(1-Hydroxy-2-methylpropan-2-yl)benzenesulfonamide AZIZ-UR-REHMAN 1,* , NADIA ABBAS 1 , MUHAMMAD ATHAR ABBASI 1 , HIRA KHALID 1 , KHALID MOHAMMED KHAN 2 , MUHAMMAD ASHRAF 3 , IRSHAD AHMAD 4 and SYEDA ABIDA EJAZ 4 1 Department of Chemistry, Government College University, Lahore-54000, Pakistan 2 HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan 3 Department of Biochemistry and Biotechnology, The Islamia University of Bahawalpur, Bahawalpur-63100, Pakistan 4 Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur-63100, Pakistan *Corresponding author: Tel: +92 42 111000010; Ext. 449; E-mail: azizryk@yahoo.com (Received: 22 February 2012; Accepted: 17 December 2012) AJC-12569 In the present study, a series of N-substituted derivative of N-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide was synthesized. Firstly, the reaction of 2-amino-2-methyl propan-1-ol (1) with benzenesulfonyl chloride (2) yielded N-(1-hydroxy-2-methylpropan-2- yl)benzene sulfonamide (3) and secondly on treatment with different electrophiles (4a-i) in the presence of N,N-dimethyl formamide and sodium hydride which act as a base furnished into N-substituted derivatives of N-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide (5a-i). All these derivatives along with their parent compounds were characterized by IR, EI-MS and 1 H NMR spectra. These compounds were assayed for their antioxidant activities by using 2,2-diphenyl-1-picrylhydrazil (DPPH) scavenging and other biological activities via screening them against acetylcholinesterase, butyrylcholinesterase and lipoxygenase enzymes, however, these showed prominent activity against butyrylcholinesterase enzyme. It is clearly evident from the results that compounds, N-(butan-2-yl)-N-(1-hydroxy-2-methylpropan- 2-yl)benzene sulfonamide (5e) and N-(allyl)-N-(1-hydroxy-2-methylpropan-2-yl)benzenesulfonamide (5f) were found to be potent inhibitor having IC50 value of 65.47 ± 0.69 and 79.36 ± 0.92 μmol, respectively, relative to eserine, a reference standard with IC50 value of 0.85 ± 0.001 μmol. These two compounds 5e and 5f were also showed good scavenging activity against DPPH. Key Words: 2-Amino-2-methyl propan-1-ol, Benzenesulfonyl chloride, Sulfonamides, Butyrylcholinesterase enzyme, DPPH. enzymes which comprise serine hydrolases. The different substrates specificities and inhibitors for these enzymes are due to the differences in amino acid residues of the active sites of AChE and BChE. The enzyme system is responsible for the termination of acetylcholine at cholinergic synapses. These are key components of cholinergic brain synapses and neuro- muscular junctions. The main function of AChE and BChE is to catalyze the hydrolysis of the neurotransmitter acetylcholine and termination of the nerve impulse in cholinergic synapses 7 . It has been found that BChE is present in extensively higher quantities in Alzheimer's plaques than in the normal age related non-dementia of brains. H1 and H2 receptor antagonists possess AChE inhibitory activities. Cholinesterase inhibitors raise the amount of acetylcholine accessible for neuronal and neuro- muscular transmission through their capacity to reversibly or irreversibly 8 . Hence, the search for new cholinesterase inhibitors is considered a significant and ongoing strategy to introduce new drug candidates for the treatment of Alzheimer's disease and other associated diseases 9 . Asian Journal of Chemistry; Vol. 25, No. 6 (2013), 3289-3293 http://dx.doi.org/10.14233/ajchem.2013.13642