Synthesis of benzoyl and halobenzoyl thiourea bearing alpha and beta alanine and its antimicrobial and antioxidant activities

Abstract

A series of benzoyl thiourea and halobenzoyl thiourea bearing α- and β-alanine with different sizes and positions of halogen atoms substituted at benzene ring have been successfully synthesized and characterized using CHNS micro elemental analysis and spectroscopic methods, including Fourier Transform Infrared (FTIR), Ultraviolet (UV), 1H- and 13C-Nuclear Magnetic Resonance (NMR). Micro elemental analysis data of the compounds were in agreement with the theoretical values. The FTIR spectra showed the ν(NH), ν(C=OOH), ν(C=ONH) and ν(C=S) bands at around 3000 cm-1, 1700 cm-1, 1600 cm-1 and 700 cm-1, respectively. The UV spectra indicated the presence of carbonyl and thione peaks at around 220 - 250 nm and 270 - 280 nm, respectively. The 1H-NMR spectra exhibited the peaks of aliphatic (δH 1 – 4 ppm), aromatic (δH 7 - 8 ppm) and C=OOH (δH 12 ppm) proton resonances. Meanwhile, the 13C-NMR spectra showed the peaks of aliphatic (δC 17 - 50 ppm), aromatic (δC 110 – 160 ppm), C=ONH (δC 165 -169 ppm), C=OOH (δC 173 ppm) and C=S (δC 180 ppm) carbon resonances. Antibacterial and antifungal activities have been evaluated by zone of inhibition, minimum inhibition concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC) studies. The compounds showed moderate antibacterial activity against B. cereus and S. epidermidis and weak activity against E. coli and P. aeruginosa. Moderate to good antifungal activity against T. mentagrophytes and weak activity against C. albicans have been observed. The inclusion of fluorine and α-alanine has enhanced the antimicrobial activity due to lipophilicity of fluorine atom and optimum shape and size of α-alanine, respectively. The compounds exerted weak antioxidant activity in DPPH scavenging test and moderate to good activity in β-carotene bleaching test. The inclusion of fluorine and β-alanine substituents has enhanced the DPPH scavenging activity with an IC50 of 2 – 4 mg/ml and 2 – 5 mg/ml, respectively. Meanwhile, the presence of chlorine at ortho, bromine at meta and fluorine at para positions showed higher β-carotene bleaching activity at 60 – 74 %, 62 - 63 % and 52 – 76 %, respectively. In addition, the introduction at α-alanine in ortho and β-alanine in para substituted compounds has increased the β-carotene bleaching activity at 61 – 74 % and 43 – 76 %, respectively.