Schiff’s Base of Different Sulfonamides

Abstract

Schiff’s bases of sulfonamides represent a vital class of biologically active compounds with diverse pharmacological applications. Sulfonamides, initially developed as potent antibacterial agents, have been modified through Schiff’s base formation to enhance their therapeutic potential while minimizing adverse effects. Schiff’s bases, also known as azomethines (-C=N-), are synthesized by condensing sulfonamide derivatives with aldehydes or ketones under controlled reaction conditions. These compounds exhibit remarkable structural versatility, allowing them to form stable metal complexes with transition metals such as Cu, Co, Ni, and Zn. The chelation of Schiff’s base ligands with metal ions often results in enhanced bioactivity, attributed to increased lipophilicity and improved interactions with biological targets. This Article comprehensively discusses the synthesis, structural characterization, and pharmacological significance of Schiff’s bases derived from sulfonamides. Various synthetic strategies, including acid/base-catalyzed condensation and metal complexation, are explored alongside their spectroscopic characterization using FT-IR, NMR, and mass spectrometry. The biological activities of sulfonamide-based Schiff’s bases are critically evaluated, highlighting their antimicrobial, anticancer, anti-inflammatory, antitubercular, and antiviral properties. Studies indicate that Schiff’s bases exhibit superior pharmacological effects compared to their parent sulfonamides, particularly in their metal-coordinated forms. The findings underscore the potential of Schiff’s base metal complexes as promising candidates for drug development. Further research into their mechanism of action, pharmacokinetics, and clinical applications is necessary to optimize their therapeutic efficacy. This Article aims to provide valuable insights into the expanding role of Schiff’s bases in medicinal chemistry.

Keywords

Introduction

The first class of clinically used, potent antibacterial medications were sulfonamides, or "sulfa-drugs," which paved the way for antibiotics in the medical field. Sulfa-drugs are still one of the most significant medication classes, and research has continued to harness their antibacterial capabilities by striking a balance between pharmacological efficacy and decreased toxicity. However, their use decreased in the early part of this decade due to some well-known adverse effects.^[1-3] SCHIFF'S Base, a versatile substance discovered by physicist Hugo SCHIFF'S, is formed when important amines accumulate with carbonyl mixtures under clear-cut reaction circumstances. They are also known as azomethine (-C=N-) or imine. Aldehydes cause SCHIFF'S base ligands to form more quickly than ketones. Focus on SCHIFF'S basis has been completed due to its highly flexible personnel and diverse designs. Sturdy structures with metal particles make up SCHIFF'S basis. Many SCHIFF'S bases exhibit synergistic activity in various responses at very high temperatures and in the presence of moisture. SCHIFF'S bases containing sulfonamides also exhibit several organic qualities, such as antimicrobial, anticonvulsant, antitubercular, anticancer, cell reinforcement, antimalarial, antibacterial, antiviral, antitumor, anti-inflammatory, and anthelmintic.^[4]

SYNTHESIS OF SCHIFF’S BASES

When an aldehyde or ketone reacts with an amine by base or corrosive catalysis, or after heat and water is ejected, a SCHIFF'S base is formed. Unlike aliphatic aldehydes, fragrant aldehydes have a structure that is persistent due to their strong formation.^[4]

Figure 1:General synthesis of SCHIFF’S base

SYNTHESIS OF SOME SULFONAMIDES-BASED SCHIFF’S BASES :

By refluxing 3-aminobenzenesulphonamide with 2-hydroxy-7-methylquinoline-3-carbaldehyde and 2-hydroxy-7-methoxyquinoline-3-carbaldehyde in ethanol using con. H2SO4 as a catalyst for 5 hours at 75 °C, Athar et al. created the SCHIFF'S base ligands, 3-{[(1E)-(2-hydroxy-7-methylquinolin-3-yl)methylene]amino}benzenesulphonamide and 3-{[(1E)-(2-hydroxy-7-methoxyquinolin-3-yl)methylene]amino}benzenesulphonamide. For five to seven hours at 70 to 75 degrees Celsius, the resulting SCHIFF'S bases were refluxed with Cu, Co, Ni, and Zn salts in a 2:1 ratio. Gram-positive bacteria like Bacillus cereus and Streptococcus pneumoniae, as well as gram-negative bacteria like Escherichia coli and Klebsiella pneumoniae, were tested for the antibacterial activity of the synthesized ligand and complexes using the disc diffusion technique. The findings demonstrated that the metal chelates outperformed the SCHIFF'S base ligands in terms of antibacterial activity.^[5]

Figure 2: 3-{[(1E)-(2-hydroxy-7-methyl/methoxy quinolin 3yl)methylene]amino}benzenesulphonamide SCHIFF’S base

Figure 3:Synthesis of sulphathiazole-based SCHIFF’S base metal complexes

Figure 4:Synthesis of Sulphamethoxazole-5-bromosalicylaldehyde SCHIFF’S base

Figure 5:Synthesis of sulphanilamide-salicylaldehyde SCHIFF’S base metal complexes

BIOLOGICAL ACTIVITIES SHOWN BY SULFONAMIDES-BASED SCHIFF’S BASES:

Schiff's bases exhibit antimicrobial, anticancer, antituberculosis, antiviral, and anti-inflammatory biological activities.^[9-15]

CONCLUSION

Because SCHIFF'S bases include azomethine nitrogen, they are an important class of ligands in coordination chemistry and are easy to synthesize with inexpensive catalysts. In coordination chemistry, SCHIFF'S base ligands have garnered a lot of interest due to their easy synthesis, broad availability, and advantageous electronic properties. Sulphonamides' efficient oral absorption and urine excretion make them an important class of drug-like chemical compounds with wide biological importance. The production and pharmacological uses of SCHIFF'S base metal complexes made from sulfanilamide are discussed in this article. There are many medicinal uses for the sulphonamide SCHIFF'S base metal complexes because of its reduced toxicity, increased reactivity, and reduced cost. According to the study, the metal complexes and SCHIFF'S bases made from sulphonamide derivatives had superior pharmacological activities with fewer adverse effects. In particular, the pharmacological effects of the coordinated metal complexes were better than those of the uncoordinated SCHIFF'S bases. Consequently, it would be advantageous to take sulphonamides into account while creating new organic and inorganic molecules.

REFERENCES

1. Mojzych M, Tarasiuk P, Kotwica-Mojzych K, Rafiq M, Seo S-Y, Nicewicz M, et al. Synthesis of chiral pyrazolo[4,3-e][1,2,4]triazine sulfonamides with tyrosinase and urease inhibitory activity. J Enzyme Inhib Med Chem. 2017;32(1):99–105.
2. Rauf F, Ahmed F, Qureshi A, Khan A, Qadir M, Choudhary M, et al. Synthesis and urease inhibition studies of barbituric and thiobarbituric acid derived sulphonamides. J Chin Chem Soc. 2011;58(4):528–37.
3. Begum F, Almandil NB, Lodhi MA, Khan KM, Hameed A, Perveen S. Synthesis and urease inhibitory potential of benzophenone sulfonamide hybrid in vitro and in silico. Bioorg Med Chem. 2019;27(5):1009–22.
4. Bhattacharyya NK, Dutta D, Biswas J. A review on synthesis and biological activity of Schiff’s bases. Indian J Chem Sect B. 2021;60(11):1478–89.
5. Athar A, Khattak AK, Batool W, Ullah F, Haq ZZ, Ullah MA, et al. Transition metal complexes of sulfonamide-based Schiff’s bases: preparation, characterization and antibacterial activity. Mor J Chem. 2016;4(4):945–53.
6. Anacona JR, Rodriguez JL, Camus J. Synthesis, characterization and antibacterial activity of a Schiff’s base derived from cephalexin and sulphathiazole and its transition metal complexes. Spectrochim Acta A Mol Biomol Spectrosc. 2014;129:96–102.
7. Chohan ZH, Shad HA, Supuran CT. Synthesis, characterization and biological studies of sulfonamide Schiff’s bases and some of their metal derivatives. J Enzyme Inhib Med Chem. 2012;27(1):58–68.
8. Ul-Hassan M, Scozzafava A, Chohan ZH, Supuran CT. Carbonic anhydrase inhibitors: metal complexes of a sulfanilamide derived Schiff’s base and their interaction with isozymes I, II and IV. J Enzyme Inhib. 2001;16(6):499–505.
9. Wu H, Jia F, Kou F, Liu B, Yuan J, Bai Y. A Schiff’s base N-(2-hydroxylacetophenone)-3-oxapentane-1,5-diamine and its copper(II) coordination polymer: synthesis, crystal structure, antioxidation, and DNA-binding properties. J Coord Chem. 2011;64(20):3454–64.
10. Kulkarni RG, Achaiah G, Sastry GN. Novel targets for anti-inflammatory and antiarthritic agents. Curr Pharm Des. 2006;12(19):2437–54.
11. Patil KR, Patil CR. Anti-inflammatory activity of bartogenic acid containing fraction of fruits of Barringtonia racemosa Roxb. in acute and chronic animal models of inflammation. J Tradit Complement Med. 2017;7(1):86–93.
12. Shelke VA, Jadhav SM, Patharkar VR, Shankarwar SG, Munde AS, Chondhekar TK. Synthesis, spectroscopic characterization and thermal studies of some rare earth metal complexes of unsymmetrical tetradentate Schiff’s base ligand. Arab J Chem. 2012;5(4):501–7.
13. Sharma M, Chauhan K, Srivastava RK, Singh SV, Srivastava K, Saxena JK, et al. Design and synthesis of a new class of 4-aminoquinolinyl- and 9-anilinoacridinyl Schiff’s base hydrazones as potent antimalarial agents. Chem Biol Drug Des. 2014;84(2):175–81.
14. Widyastuti DA, Yusuf Y. The effect of power rate microwave heating on limestone carbonated hydroxyapatite scaffold using gas foaming method. Adv Mater Res. 2024;1179:11–8.
15. Prakash A, Adhikari D. Application of Schiff’s bases and their metal complexes - a review. Int J Chem Tech Res. 2011;3(4):1891–6.