Synthesis, Antitubercular Evaluation of New 2,3-(4-Aminobenzamido)benzoic Acid Derivatives

Objective: The escalating challenge posed by multidrug-resistant tuberculosis (MDR-TB) necessitates the discovery of potent treatment agents. This study aims to synthesize, characterize, and evaluate the antitubercular potential of 33 novel 2,3-(4-aminobenzamido)benzoic acid derivatives (1–33). Methods: The synthesis involved a three-stage reaction series starting with p-aminobenzoic acid treated with concentrated hydrochloric acid to obtain its salt. This was further modified to ammonium benzoyl chloride using thionyl chloride. The ammonium benzoyl chloride was then condensed with 2 or 3 benzoic acids to yield the desired 2,3-(4-aminobenzamido)benzoic acid derivatives. The structures of these compounds were elucidated using FT-IR, HR-MS, ¹H, and ¹³C NMR. Their antituberculosis activity was assessed using the Alamar blue dye assay against Mycobacterium tuberculosis H37RV. Results and Discussion: Out of the 33 synthesized compounds, 12 showed sensitivity to Mycobacterium tuberculosis (MTB). Notably, five compounds (14), (18), (19), (26), and (30) demonstrated significant potency, with minimal inhibitory concentrations (MICs) of 1.6 µg/mL, nearly 50 times lower than the standard drug. These results strongly suggest the potential of these compounds as effective tuberculosis therapeutics. Conclusions: The synthesized series of 2,3-(4-aminobenzamido)benzoic acid derivatives have shown promising antituberculosis activity. Specifically, compounds (14), (18), (19), (26), and (30) exhibited noteworthy potency. It is crucial that future research focuses on further screening the active compounds (2–4), (10), (14), (18), (19), (21), (26), (28), (30), and (33) for antimicrobial strains and evaluating compounds (14), (18), (19), (26), and (30) using the DHFR enzyme-specific assay to advance the development of effective tuberculosis treatments.