Medicinal Chemistry

The synthesis of various N-aryl and N-heteroaryl substituted benzene sulphonamide 4a-e is reported. The intermediate benzene sulphonamide 2 was obtained by the reaction of benzene sulphonyl chloride 1 with ammonium hydroxide. The coupling reaction of the benzene sulphonamide 2 with various aryl halides and heteroaryl halides 3a-e via tandem catalysis gave the N-aryl and N-heteroaryl benzene sulphonamide derivatives 4a-e. The compounds were characterized using FTIR, 1HNMR and 13CNMR. These sulphonamides 2 and 4a-e were tested for antibacterial activities against Staphylococcus aureus, Enterococcus faecalis, Salmonella typhi, Klebsiella pneumonia, Pseudomonas aeruginosa, and Escherichia coli. The antifungal activities were tested against Candida albican and Aspergillus niger using Agar cup diffusion technique. Some of the tested compounds showed significant antimicrobial activities with improved potency after arylation, though none of the sulphonamides was as active as standard tetracycline and ketoconazole for antibacterial and antifungal activities respectively.

Two simple, accurate and precise spectrophotometric methods for the quantitative analysis of mesalazine (MSZ) in pharmaceutical formulation have been described. The first method (A) is based on the charge transfer reaction with alizarin red sulphonate (ARS) in the solution of pH 8.0 to form a violet product showing maximum absorbance at 600 nm. The second method (B) is a derivatisation method involving reaction of MSZ with 1,2-naphthoquinone-4- sulphonate (NQS) in alkaline medium at pH 12.0 to form an orange product exhibiting maximum absorbance at 470 nm. All variables affecting the reactions were studied and optimized. Beer's law was obeyed in the concentration ranges of 15-97.5 and 2-22 μg/mL for methods A and B, respectively. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. The two methods were successfully applied to the determination of MSZ in pharmaceutical formulation.

A new naturally occurring N1, N6-dihydrocinnamyl putrescine bisamide, JBIR-94, along with nine structural analogs and a series of substituted phenyl and alkyl putrescine bisamides have been synthesized from putrescine and appropriately substituted carboxylic acids, through carboxylic acid chlorides. Antimicrobial, 5-Lipooxygenase enzyme inhibitory and antioxidant studies were performed for all synthesized compounds. Dihydrocinnamyl series of putrescine bisamides (4a-4i) showed good bioactivities compared to substituted phenyl (6a-6g) and diakyl (6h-6j) series of compounds. Among all compounds, 4h (methylenedioxy analog) and 4a (JBIR-94) showed good antimicrobial, antiinflammatoryand antioxidant activities.

Diabetes mellitus is one of the common metabolic diseases in the world associated with high blood sugar levels. Diabetes is categorized into type I and type II. The common type of diabetes is type II diabetes that is insulin dependent. On a global level, plant sources employed in traditional medicine are believed to be valuable to treat diseases. Ancient physicians had mastered the science of managing diabetes by balancing herbs or plants as food and medicine. Modern therapies are too costly to be practical for diabetic referrers. The ethanopharmacological use of herbal remedies for the treatment of diabetes is an area of study with a huge potential in the development of alternative, inexpensive therapies for treating the disease. The present paper reviews various traditionally used medicinal plants and their modes of action. Medicinal plants such as Anacardium occidentale, Coccinia indica, Gymnema sylvestre, Panax ginseng, Salacia spp. etc. with their active compounds such as salacinol, kotalanol, glucoside jamboline, phytol, myoinositol, scyllitol, pryones, stigmat-4-en-3-one, cholest-4-en-3-one etc. showed antidiabetic activity. The different modes of action by these compounds include inhibition of intestinal amylase-α-glucosidase, increase of β-cell stimulation, increase in number of insulin receptors, increase in insulin receptor binding affinity to the released insulin, fighting against free radicals to decrease cell damage and decrease of hepatic glucose by decreasing gluconeogenesis and glycogenolysis.

A series of newly naphthoquinone derivatives were synthesized using 2,3- dihydro-2,3-epoxy-1,4-naphthoquinone (1) as a starting material. The corresponding acetophenyl derivative 7 was used as building blocks for synthesis of different heterocycles incorporated naphthoquinone moiety. The newly synthesized compounds were characterized utilizing the corresponding analytical and spectroscopic data and evaluated as antioxidant activity by superoxide (NBT) free radical scavenging methods. Compounds 21, 22 promosing the more potent antioxidant agents than ascorbic acid. Moreover, the newly synthesized quinones were tested for their Cytotoxicity by brine shrimp lethality bioassay. Quinone derivatives 3, 12, 18, 23 were proven to be the best potent cytotoxic agents.