DESIGN, SYNTHESIS, SPECTRAL CHARACTERIZATION, AND STRUCTURE– ACTIVITY RELATIONSHIP STUDIES OF NOVEL SULFAMETHOXAZOLE-BASED THIAZOLIDINONE DERIVATIVES AS POTENTIAL ANTIBACTERIAL AGENTS

Rishabh Tyagi, Mrs. Renu*, Mr. Ravi Kumar Saini, Dr. Omprakash Goshain, Mr. Gurjeet Singh

ABSTRACT

Background: The rapid emergence of antimicrobial resistance has significantly reduced the therapeutic
effectiveness of existing antibiotics, creating an urgent need for the development of new antibacterial agents.
Sulfonamides, particularly Sulfamethoxazole, remain important due to their inhibition of bacterial folic acid
biosynthesis; however, increasing resistance has limited their clinical utility. Objective: The present study aimed to
design, synthesize, characterize, and evaluate novel sulfamethoxazole derivatives containing Schiff base,
thiazolidinone, and chalcone pharmacophores for enhanced antibacterial activity. Methods: A series of
sulfamethoxazole derivatives were synthesized through a multistep synthetic pathway. Initially, sulfamethoxazole
was condensed with substituted benzaldehydes to form Schiff base intermediates (M1). These intermediates were
cyclized with thioglycolic acid to obtain thiazolidinone derivatives (M2), which were further modified to produce
chalcone analogues (M3a–f). The synthesized compounds were characterized using Fourier-transform infrared
spectroscopy (FT-IR), proton nuclear magnetic resonance (¹H-NMR), and elemental (CHNS) analysis.
Antibacterial activity was evaluated in vitro against selected Gram-positive and Gram-negative bacterial strains.
Results: Spectral and elemental analyses confirmed the successful synthesis of the target compounds. Biological
evaluation revealed that several synthesized derivatives exhibited improved antibacterial activity compared to
sulfamethoxazole. Structure–activity relationship (SAR) studies demonstrated that compounds containing electronwithdrawing
substituents such as –Cl and –NO₂ showed superior antibacterial activity, while electron-donating
substituents produced moderate effects. The incorporation of thiazolidinone and chalcone moieties significantly
enhanced biological activity. Conclusion: The synthesized sulfamethoxazole derivatives demonstrated promising
antibacterial potential, particularly those bearing electron-withdrawing substituents. The study suggests that
structural modification of sulfamethoxazole through incorporation of Schiff base, thiazolidinone, and chalcone
pharmacophores may provide an effective strategy for the development of novel antibacterial agents to combat
antimicrobial resistance.

Keywords: Sulfamethoxazole; Schiff base; Thiazolidinone; Chalcone derivatives; Antibacterial activity; Structure–activity relationship (SAR); Antimicrobial resistance; Sulfonamide derivatives; Gram-positive bacteria; Gram-negative bacteria.