Sortase A (SrtA) is an attractive target for developing new anti-infective drugs that aim to interfere with essential virulence mechanisms, such as adhesion to host cells and biofilm formation. Herein, twenty hydroxy, nitro, bromo, fluoro, and methoxy substituted chalcone compounds were synthesized, antimicrobial activities and molecular modeling strategies against the SrtA enzyme were investigated. The most active compounds were found to be T2, T4, and T19 against Streptococcus mutans (S. mutans) with MIC values of 1.93, 3.8, 3.94 μg/mL, and docking scores of -6.46, -6.63, -6.73 kcal/mol, respectively. Also, these three active compounds showed better activity than the chlorohexidine (CHX) (MIC value: 4.88 μg/mL, docking score: -6.29 kcal/mol) in both in vitro and in silico. Structural stability and binding free energy analysis of S.mutans SrtA with active compounds were measured by molecular dynamic (MD) simulations throughout 100 nanoseconds (ns) time. It was observed that the stability of the critical interactions between these compounds and the target enzyme was preserved. To prove further, in vivo biological evaluation studies could be conducted for the most promising precursor compounds T2, T4, and T19, and it might open new avenues to the discovery of more potent SrtA inhibitors.

Download full-text PDF

Source
http://dx.doi.org/10.1002/cbdv.202301659DOI Listing

Publication Analysis

Top Keywords

active compounds
12
antimicrobial activities
8
activities molecular
8
molecular modeling
8
compounds t19
8
compounds
6
synthesis antimicrobial
4
modeling studies
4
studies agents
4
agents sortase
4

Similar Publications

A review of cardioprotective effect of ginsenosides in chemotherapy-induced cardiotoxicity.

Biomed Eng Online

December 2024

Department of Stem Cells Technology and Tissue Regeneration, Faculty of Interdisciplinary Science and Technologies, Tarbiat Modares University, Tehran, 15614, Iran.

Chemotherapy-induced cardiotoxicity is a significant concern in cancer treatment, as certain chemotherapeutic agents can have adverse effects on the cardiovascular system. This can lead to a range of cardiac complications, including heart failure, arrhythmias, myocardial dysfunction, pericardial complications, and vascular toxicity. Strategies to mitigate chemotherapy-induced cardiotoxicity may include the use of cardioprotective agents (e.

View Article and Find Full Text PDF

Background: Periodontitis is an inflammatory disease causing destruction of periodontal tissues. Controlling inflammation is crucial for periodontitis treatment. Prohibitins (PHBs) are emerging targets in the treatment of inflammatory diseases.

View Article and Find Full Text PDF

In Salmonella Typhimurium, efflux pump proteins, such as AcrD actively expel drugs and hazardous chemicals from bacterial cells, resulting in treatment failure and the emergence of antibiotic-resistant variants. Focusing on AcrD may lead to the development of novel antimicrobials against multidrug-resistant bacteria. However, challenges persist in achieving high selectivity, low toxicity, and effective bacterial penetration.

View Article and Find Full Text PDF

The large and rapid increase in the incidence and mortality of colorectal cancer (CRC) demonstrates the urgent need for new drugs with higher efficacy to treat CRC. However, the lack of applicable and reliable preclinical models significantly hinders the progress of drug development. Patient-derived xenograft (PDX) models are currently considered reliable in vivo preclinical models for predicting drug efficacy in cancer patients.

View Article and Find Full Text PDF

Sesquiterpene lactones from Seriphidium transiliense and their anti-inflammation activity.

Fitoterapia

December 2024

The State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China. Electronic address:

Six undescribed sesquiterpene lactones (1-6) and fifteen known compounds (7-21) were isolated from Seriphidium transiliense. The chemical structures were determined by extensive NMR spectroscopic data, HRESIMS, ECD and X-ray diffraction. Among the known compounds, twelve known compounds were isolated for the first time from this plant, including taurine (9), 11-epitaurin (10), α-santonin (11), artesin (13), 11-epiartesin (14), 1α-hydroxy-3β-acetoxyeudesm-4-en-6β, 7α, 11βH-12, 6-olide (15), 1α-hydroxy-3β-acetoxyeudesm-4-en-6β, 7α, 11αH-12, 6-olide (16), artegallin (17), 8α-hydroxytaurin (18), 8α-acetoxytaurine (19), methyl-4α-hydroxy-11(13)-eudesmen-12-oatesaniculamoid D (20), and saniculamoid D (21).

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!