This study focussed on the synthesis of sulfamethoxazole derivatives and their biological evaluation. The sulfamethoxazole derivatives were successfully biologically evaluated against Mycobacterium tuberculosis, Staphylococcus aureus, and Chinese Hamster Ovarian (CHO) cells. The biological evaluation revealed compounds with improved antitubercular activity and antibacterial activity against S. aureus as well as safety profile when compared to the starting material, sulfamethoxazole. The most active compounds against Mycobacterium tuberculosis were3q with 92 inhibition followed by 3s (90), 3k (88), 3t (85), and 3o (84).

Background: Tuberculosis (TB), a disease caused by the bacillus bacteria Mycobacterium tuberculosis is one of the major contributors of ill health in the world. TB is ranked in the top 10 causes of death globally and it is the leading killer associated with a single infectious agent. According to the World Health Organization (WHO), global number of deaths associated with TB have been slowly declining with 1.3 million in reported 2016 and 2017, and 1.2 million reported in 2018 and 2019. Objective: The synthesis, characterisation, biological evaluations, and the prediction of ADMET properties of the novel benzylamine derivatives. Methods: Commercially available reagents and solvents were purchased from Sigma Aldrich and Merck (South Africa). All chemicals were used as received, unless otherwise stated. The synthesised crude compounds were purified by flash silica gel column chromatography (5 – 30% ethyl acetate in hexane). The successful formation and purity of the synthesised compounds was confirmed by NMR, HRMS and melting point. Results: The respective organic compounds were synthesised by treating 3-ethoxysalcyladehyde, 5-bromo-3-ethoxysalcyladehyde, 5-chloro-3-ethoxysalcyladehyde with various aromatic amines and the products were obtained in good to excellent yields. The ¹H and ¹³C NMR spectra of all the products showed the appearance of the methylene signals ranging from 3.88 – 4.68 ppm and 42.25 – 52.57 ppm respectively. Additionally, most compounds showed anti-Mycobacterium tuberculosis activity that ranged between 20 and 28 µM. Conclusion: A total of 36 compounds were synthesised and successfully biologically evaluated against Mycobacterium tuberculosis (Mtb) H37RV strain. All compounds showed activity against Mtb at concentrations of > 20 µM < 28 µM with the exception of compound one that was active against Mtb at higher concentration (MIC90 > 125 µM).

Indole-containing compounds are widely distributed in the plant and animal kingdom, and their biological activity and pharmacological properties have prompted research into their chemical properties. This study developed a one-pot methodology for the synthesis of 3-aminoindole derivatives using copper- and ligand-free Sonogashira cross-coupling reaction conditions. The synthesised 3-aminoindole derivatives were confirmed using spectroscopic techniques. The resulting 3-aminoindole derivatives were biologically evaluated against Mycobacterium tuberculosis and Plasmodium falciparum. For example, indole derivatives 10a (7.813µM) and 10j (8.332µM) were the most active derivatives in the CAS and ADC media, respectively.