Synthetic indole derivatives as an antibacterial agent inhibiting respiratory metabolism of multidrug-resistant gram-positive bacteria.

Autor: Chandal N; Clinical Microbiology & Antimicrobial Research Laboratory, CSIR- Institute of Microbial Technology, Sector 39-A, Chandigarh, 160036, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India., Kalia R; Department of Natural Products, National Institute of Pharmaceutical Education and Research Mohali, 160062, Mohali, India., Dey A; Department of Natural Products, National Institute of Pharmaceutical Education and Research Mohali, 160062, Mohali, India., Tambat R; Clinical Microbiology & Antimicrobial Research Laboratory, CSIR- Institute of Microbial Technology, Sector 39-A, Chandigarh, 160036, India.; Department of Chemistry and Biochemistry, University of Oklahoma, Norman, OK, USA., Mahey N; Clinical Microbiology & Antimicrobial Research Laboratory, CSIR- Institute of Microbial Technology, Sector 39-A, Chandigarh, 160036, India.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India., Jachak S; Department of Natural Products, National Institute of Pharmaceutical Education and Research Mohali, 160062, Mohali, India., Nandanwar H; Clinical Microbiology & Antimicrobial Research Laboratory, CSIR- Institute of Microbial Technology, Sector 39-A, Chandigarh, 160036, India. hemraj@imtech.res.in.; Academy of Scientific & Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, 201002, India. hemraj@imtech.res.in.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2024 Nov 12; Vol. 7 (1), pp. 1489. Date of Electronic Publication: 2024 Nov 12.
DOI: 10.1038/s42003-024-06996-8
Abstrakt: The survival of modern medicine depends heavily on the effective prevention and treatment of bacterial infections, are threatened by antibacterial resistance. The increasing use of antibiotics and lack of stewardship have led to an increase in antibiotic-resistant pathogens, so the growing issue of resistance can be resolved by emphasizing chemically synthesized antibiotics. This study discovered SMJ-2, a synthetic indole derivative, is effective against all multidrug-resistant gram-positive bacteria. SMJ-2 has multiple targets of action, but the primary mechanism inhibits respiratory metabolism and membrane potential disruption. SMJ-2 was discovered to interfere with the mevalonate pathway, ultimately preventing the synthesis of farnesyl diphosphate, a precursor to the antioxidant staphyloxanthin, eventually releasing reactive oxygen species, and leading phagocytic cells to destroy pathogens. Additionally, no discernible biochemical and histopathological alterations were found in the mouse acute toxicity model. This study emphasizes mechanistic insights into SMJ-2 as a potential antibacterial with an unusual method of action.
Competing Interests: Competing interests The authors declare no competing interests. Ethics approval This study was carried out in compliance with the recommendations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). The protocol (IAEC/21/05) was approved by the Institute of Microbial Technology’s Institutional Animal Ethics Committee in Chandigarh, India. We have complied with all relevant ethical regulations for animal use. We have used female, BALB/c mice of 5–7 weeks in our experiments. Randomization and blinding were not regarded as necessary for infection animal models. During the histopathology investigation, the observer was unaware of the control and treatment groups.
(© 2024. The Author(s).)
Databáze: MEDLINE
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