Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors

Abstract

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

Pharmacokinetics, Mechanism, and Docking Study of Antioxidant Aryl‐Bisthiourea Derivatives for Alzheimer's Disease

“…The derivatives with high AMES toxicity prediction values were found to be more toxic. [26] In this pharmacokinetics study, all the ArBTU derivatives showed hepatotoxic behavior without any skin-sensitive activity. The ADMET study proved that the ArBTU derivatives exhibited virtuous lead-like potential but slight hepatotoxic.…”

Synthesis and biological evaluation of new derivatives of thieno-thiazole and dihydrothiazolo-thiazole scaffolds integrated with a pyrazoline nucleus as anticancer and multi-targeting kinase inhibitors

“…The biological potential of the newly prepared target structures was inspected toward the examined organisms and expressed as the diameter of the inhibition zones due to the agar plate diffusion technique. [64][65][66][67][68][69] More details in the ESI. † 2.2.5.1.…”

Bis-Thiourea Quaternary Ammonium Salts as Potential Agents against Bacterial Strains from Food and Environmental Matrices

“…All strains were maintained as freeze-dried stocks in reconstituted (11% w/v) skim milk, containing 0.1% w/v ascorbic acid and routinely cultivated in optimal growth conditions [35] (Table 2). These bacteria were chosen to represent the diversity of species of food-borne (labels 1-22; 31-35) and environment-borne (labels [23][24][25][26][27][28][29][30]36) Gram-positive and Gram-negative bacteria.…”

“…A biocide is only active when it can pass through the outer layers of the cell, the structure and composition of which allows it to act as a barrier. In the literature, thiourea derivatives with antibacterial activity tested in vitro against pathogenic strains both Gram-positive ( Staphylococcus aureus, Bacillus subtilis and Bacillus cereus ) and Gram-negative ( Escherichia coli, Proteus vulgaris and Pseudomonas aeruginosa ) have been described and the results have shown considerable activity and a broad spectrum of action [ 28 , 29 ]. The presence of two thiourea moieties, as in the case of bis derivatives, is thought to have a better antibacterial activity, probably due to the fact that the C = S and NH groups of thiourea are easily protonable in acidic conditions and can react with the carboxyl and phosphate groups of the bacterial surface, thus improving the activity.…”