Sulfonamide-salicylaldehyde Imines Active Against methicillin- and trimethoprim/sulfonamide-resistant Staphylococci

Abstract

Background: Increasing resistance has resulted in an urgent need for new antimicrobial drugs. A systematic me-too approach was chosen to modify clinically used sulfonamides to obtain their imines. Methods & results: Twenty-five compounds were synthesized and evaluated for their antibacterial activity. The most active compounds were also investigated against methicillin- and trimethoprim/sulfamethoxazole (SMX)-resistant Gram-positive species. Staphylococci shared the highest susceptibility including resistant strains with minimum inhibitory concentrations from 3.91 μM (≥2.39 μg ml-1). Crucially, the compounds inhibit MRSA and trimethoprim/SMX-resistant Staphylococci without any cross-resistance. Modification of parent sulfonamides turned a bacteriostatic effect into a bactericidal effect. Toxicity for HepG2 and hemolytic properties were also determined. Conclusions: The presence of a dihalogenated salicylidene moiety is required for optimal activity. Based on toxicity, promising derivatives for further investigation were identified.

Designing metal chelates of halogenated sulfonamide Schiff bases as potent nonplatinum anticancer drugs using spectroscopic, molecular docking and biological studies

“…This is in harmony with the spotted decrease in the activity of SB 1 or SB 2 (mono-brominated Schiff bases), and SB 3 (absence of thiazole ring) in comparison with SB 4 . Also, the substituent size (I or Br) is a crucial factor in determining the feasibility of pathogen inhibition 54,55 . Noticeably, the Gram-negative P. vulgaris bacteria showed the least susceptible character against most tested compounds (Table 5) pointing to the importance of its outer lipid membrane as an additional shield despite its thinner peptidoglycan wall 56 .…”

“…1) as deduced in the antimicrobial Sect. 8,55 . Interestingly, SB 5 (6.32 μM) exhibited threefold inhibition efficacy more than cisplatin recommending it as a promising breast anticancer drug and in accord with US NCI program (IC 50 < 10 μM) 57 www.nature.com/scientificreports/ Furthermore, a comparative study was also made to compare the cytotoxicity of some ligands (SB 1 and SB 2 ) against different human cell lines HCT-116 (colon carcinoma), HepG-2 (hepatocellular carcinoma), and MCF-7 (breast carcinoma) (Figs.…”

Synthesis, Biological Evaluation, and Docking Study of a New Series of Thiophene Derivatives Based on 3‐Oxobutanamidothiophene as an Anticancer Agent

“…Many derivatives based on 2‐aminothiophenes were tested in mammalian carcinoma cells such as PC3 (prostate cancer), HepG2 (liver carcinoma), Hep‐2 (laryngeal carcinoma), and MCF‐7 (breast cancer) [7–10] (Figure 1). Furtheromore, the thiophene moiety also shows wide biological activities, such as antibacterial, [11–13] antioxidant, antifungal, SARS‐CoV‐2 main protease inhibition, [14–17] anti‐inflammatory, [18] and anti‐tubercular [19] . Thiophene‐based dyes were also applied as sensitizers to many solar cells [20,21] .…”

Insight into the Antibacterial Action of Iodinated Imine, an Analogue of Rafoxanide: a Comprehensive Study of Its Antistaphylococcal Activity

“…Imines (Schiff bases) have been investigated largely as potential antimicrobial agents ( 18 , 19 ). We have recently designed, synthesized, and evaluated active antibacterial and antifungal imines derived from sulfonamide drugs, 4-aminobenzoic acid, and its analogues ( 20 – 23 ). Among these compounds, 3,5-dihalogenosalicylaldehyde-based imines showed promising antibacterial activity against Gram-positive bacteria, including MRSA.…”