Substitution to Position Number 2 of 4(3<i>H</i>)-Quinazolinone to Create New Derivatives and to Test the Antibacterial or Antifungal Effects

Abstract

The campaign “No action today, no cure tomorrow” against antimicrobial resistance proposed by the World Health Organization (WHO) has not only propeled people to take action to prevent antimicrobial resistance, but has also encouraged researchers to develop new antimicrobial agents. 4(3H)-quinazolinone and its derivatives belong to a group of compounds with many potential applications; this study was conducted to find new derivatives of heterocyclic 4(3H)-quinazolinone with biological effects, contributing to research on antibacterial and antifungal compounds. Using the closed-loop method between anthranilic acid and acetic anhydride, followed by reaction with aniline derivatives, a substituted product of position 3 of 4(3H)-quinazolinone was obtained, along with bromizing to replace the hydrogen of the methyl group in position 2 with dibromo. Heterocyclic derivatives such as imidazole, triazole, and thiazole were replaced from this dibromo product to obtain 19 derivatives. The structures of these derivatives were checked by modern methods such as IR, 1H-NMR, and MS. The results indicated that all of the structures were as expected, so the process of creating new derivatives from 4(3H)-quinazolinone was achieved in this study. Fourteen of the derivatives, namely 3d, 3e, 3f, 3g, 3h, 3i, 3j, 3k, 3m, 3o, 3p, 3q, 3r, and 3s, had antibacterial or antifungal effects. Among these, there were five potential derivatives: Antifungal activity was observed on A. niger by 3j and 3f (MIC: 32 μg/mL) and 3s (MIC: 64 μg/mL), and on C. albicans by 3f (MIC: 8 μg/mL); antibacterial activity was observed on S. aureus by 3p (MIC: 16 μg/mL) and 3f and 3r (MIC: 32 μg/mL), on MRSA by 3f and 3r (MIC: 32 μg/mL), and on E. coli by 3f (MIC: 32 μg/mL).

Keywords

• 4(<i>3H</i>)-quinazolinone
• heterocyclic derivatives
• synthesize heterocyclic compounds