SYNTHESIS OF METAL BASED DERIVATIVES OF SULFONAMIDES AND THEIR BIOLOGICAL EVALUATION

Abstract

The work presented in this thesis concerns the synthesis of various sulfonamide derived Schiff bases by the equimolar reaction of sulfonamides e.g., sulfamethazine, sulfadiazine, sulfathiazole, sulfanilamide, sulfamethaxazole, 4-(2-aminoethyl)benzene sulfonamide, 4- (methyl)benzenesulfonamide, sulfisoxazole and sulfaguanidine with the respective aldehydes such as 5-chlorosalicylaldehyde, 5-bromosalicylaldehyde and 2- hydroxynaphthaldehyde. The free amino group (NH2) of the sulfonamide moiety condense with the carbonyl (HC=O) group of aldehydes to achieve the target of twenty- one new sulfonamide derived Schiff base (L1)–(L21) compounds. The structures of newly synthesized sulfonamides were elucidated by their physical, spectral (IR, 1H and 13 C NMR and mass) and analytical (CHN analysis) data. X-ray diffraction studies on nine sulfonamides were carried out to confirm the structures of 4-(5-chloro-2- hydroxybenzylideneamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (L1), 4- [(E)-(5-chloro-2-hydroxybenzylidene)amino]benzenesulfonamide (L4), 4-{2-[(5-chloro- 2-hydroxybenzylidene)amino]ethyl}benzenesulfonamide (L6), 4-chloro-2-[(E)-({4-[N- (3,4-dimethylisoxazol-5-yl)sulfamoyl]phenyl}iminio)methyl]phenolate (L8), 4-[(5- bromo-2-hydroxybenzylidene)amino]-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfon amide-4-bromo-2-[(E)-({4-[(4,6-dimethyl-pyrimidin-2-yl)sulfamoyl]phenyl}iminio) methyl]phenolate (L10), 4-[(E)-(5-bromo-2-hydroxyphenyl)methylideneamino]benzene sulfonamide (L13), 4-{[(E)-(5-bromo-2-hydroxyphenyl)methylidene]amino}-N-(5- methyl-1,2-oxazol-3-yl)benzenesulfonamide benzylidene)amino]ethyl}benzenesulfonamide (L14), 15 (L ) 4-{2-[(5-bromo-2-hydroxy and 4-bromo-2-((E)-{4-[(3,4- dimethylisoxazol-5-yl)sulfamoyl]phenyliminiomethyl)phenolate (L17). The synthesized sulfonamide derived Schiff base were used as ligands for complexation reaction with a number of metalloelements [Co(II), Ni(II), Cu(II) and Zn(II)] using in a molar ratio of L : M as 2 : 1. The nature of bonding and structure of all the metal(II) complexes have been deduced by their physical (conductivity, magnetic measurements), spectral (IR, 1H and 13 C NMR and electronic) and analytical (CHN analysis) data. The result of these studies revealed an octahedral geometry for all the metal(II) complexes. Due to amorphous nature of the metal(II) complexes, their crystals could not be formed for X-ray diffraction studies. In order to evaluate the biological role of these compounds and the effect of metalloelements on the nature of their biological activity, all the synthesized compounds were screened for their in vitro antibacterial, antifungal and cytotoxic activities against four Gram–negative (Escherichia coli, Shigella flexneri, Pseudomonas aeruginosa and Salmonella typhi) and two Gram–positive (Bacillus subtilis and Staphylococcus aureus) bacterial strains and against six fungal strains (Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glabrata) using agar-well diffusion method. The result of these studies revealed that majority of the compounds showed significant (~80%) to moderate (~50%) antibacterial/antifungal activity. The activity however, was enhanced upon chelation/coordination with the metalloelements: some compounds, which were non- active, became active and moderate active became significantly active. Amongst all the compounds, the zinc(II) complexes showed the highest activity. The brine shrimp (Artemia salina) bioassay was also carried out to study in vitro cytotoxic activity. These studies revealed that several compounds displayed potent cytotoxic activity as LD50 in the range of 4.898 x 10-4 to 6.745 x 10-4 M/mL.