Synthesis and Antimicrobial Activities of N-(Heteroaryl-substituted)-p-toluenesulphonamides

A new class of N-(heteroaryl-substituted)-p-toluenesulphonamides has been synthesized exhibiting antibacterial and antifungal properties. The condensation reaction of p-toluenesulphonyl chloride 1 with appropriate substituted amino pyridines 2a–g in acetone furnished N-(heteroaryl-substituted)-p-toluenesulphonamides 3a–g. These derivatives were characterized by IR, 1H-, and 13C-NMR spectroscopy and were screened in vitro against gram-positive bacteria, gram-negative bacteria, and fungi organisms using agar-diffusion method. Results indicated improved biological activities over reference drugs such as Tetracycline (TCN) and Fluconazole (FLU). 1. Introduction Sulphonamides are known to represent a class of medicinally important compounds which are extensively used as antimicrobial, antimalarial, and anticancer agents and inhibitors of carbonic anhydrase among others [1, 2]. Before the discovery of antibiotics in the 1940s, sulphonamides were the first efficient compounds used to treat microbial infections [3]. Sulphonamides are the amides of sulphonic acid which contain the basic group –SO2NH. They have been used against most gram-positive and many gram-negative organisms, fungi, and certain protozoa [4]. Sulphonamides are used in veterinary medicines to treat infections in livestock, also used in medicinal chemistry as potential therapeutic agents for depression, sleep disorder, pains, and hypertension among others [5–7]. Clinical sulphonamides have been used for the treatment of uncomplicated urinary tract infections [8]. Interest in the pharmacological activities of sulphonamide prompted the synthesis of scaffolds of sulphonamides and their derivatives. The discovery of sulphonamides started in the early 1930s, when Gerhard Domagk [9] discovered one of the dyes, Prontosil. Prontosil’s discovery ushered in the era of antibacterial and had a profound impact on pharmaceutical research, drug laws, and medical history. Prontosil is known as prodrug [10] which was reduced to sulphanilamide. The potency of these clinically useful drugs in treatment of microbial infections and other activities encouraged the development of some more potent and significant compounds. In spite of recent advances in the development of sulphonamides as drugs, the synthesis and biological evaluation of N-heteroaryl derivatives of p-toluenesulphonamides remain largely unknown. Hence these led us to the synthesis of such new categories of p-toluenesulphonamides for evaluation of the antimicrobial activities. 2. Results and Discussion 2.1. Chemistry (Synthesis) In this present