In Vitro Antimicrobial Screening of Benzoylthioureas: Synthesis, Antibacterial Activity toward Streptococcus agalactiae and Molecular Docking Study

Abstract

Herein, twenty-six benzoylthioureas were evaluated for their antimicrobial activity against different bacterial and fungal species. Two 4-substituted benzoylthiourea, one benzoylurea and one benzoylguanidine derivatives were further synthesized to identify the most promising compound. Eight compounds were active against at least one microbial species tested. N-(butylcarbamothioyl)-benzamide (1 e) exhibited the best antimicrobial activity towards Streptococcus agalactiae (group B Streptococcus-GBS), including clinical isolates susceptible or resistant to clindamycin and/or erythromycin and azithromycin.1 e presented a bacteriostatic effect, causing morphological and ultrastructural alterations on planktonic cells, and decreased the metabolic activity of GBS biofilms. No hemolytic and cytotoxicity to mammalian cells were detected for 1 e, that also displayed drug-likeness properties. Molecular docking was performed on Streptococcus pneumoniae enoyl-ACP reductase obtained by homology modeling. 1 e showed relevant interactions with the GBS enoyl-ACP reductase enzyme. N-(butylcarbamothioyl)-benzamide may be a good starting point for the development of new antimicrobials against GBS.

Synergistic antifungal interaction of N-(butylcarbamothioyl) benzamide and amphotericin B against Cryptococcus neoformans

“…Therefore, in our ongoing search to discover new antimicrobial 10.3389/fmicb.2023.1040671 agents, in a previous study, we evaluated the antifungal activity of a series of benzoylthioureas against Candida spp. These compounds exhibited a moderate inhibitory activity on the growth of planktonic cells, with minimal inhibitory concentration (MIC) ranging from 250 to >1,000 µg/mL (Biasi-Garbin et al, 2022).…”

“…Thiourea is a class of organic compounds containing the > NC = SN < moiety that allows many chemical modifications and bonding possibilities due to the presence of nitrogen and sulfur atoms ( Zahra et al, 2022 ). Several biological activities have been attributed to thiourea derivatives, including antibacterial, antifungal, antitrypanosomal, antidiabetic, antitumor, and urease inhibitor ( Rego et al, 2018 ; Brito et al, 2020 ; Khidre and Radini, 2021 ; Pereira et al, 2021 ; Biasi-Garbin et al, 2022 ; Zahra et al, 2022 ) among others. Thiourea derivatives are thermally stable and can be produced with good efficiency from available starting compounds by simple and low-cost reactions ( Shakeel, 2016 ).…”

Antiprotozoal Activity of Benzoylthiourea Derivatives against Trypanosoma cruzi: Insights into Mechanism of Action

“…In this context, thiourea is a relevant class of sulfur-bearing substances with notable synthetic and biological versatility. Thiourea derivatives have shown promising pharmaceutical potential due to their diverse pharmacological activities, including antitumoral [ 11 ], antioxidant [ 12 ], antidiabetic [ 13 ], and antimicrobial [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ] properties. Notably, the thiourea moiety has been identified in several compounds with potential for the development of new therapeutic compounds to treat diseases caused by trypanosomatid species [ 21 , 22 , 23 ].…”