Small molecules that can restore the action of legacy antibiotics toward drug-resistant bacteria represent an area of ongoing research interest. We have previously reported indole-3-glyoxylamido and indole-3-acetamido-polyamine conjugates that exhibit intrinsic activity toward bacterial and fungal species, and the ability to enhance the action of doxycycline toward the Gram-negative bacteria ; however, these desirable activities were commonly associated with unfavorable cytotoxicity and/or red blood cell hemolytic properties. In this paper, we report the synthesis and biological investigation of a new class of α,ω-di(indole-3-carboxamido)polyamine derivatives, leading to the identification of several analogues that exhibit antimicrobial- and antibiotic-potentiating activities without detectable cytotoxic or hemolytic properties. 5-Bromo-substituted indole analogues and - were generally more broad-spectrum in their activity than others in the set, with (polyamine PA-3-6-3) being particularly notable for its anti-, , and activities (MIC ≤ 0.28 µM). The same analogue also restored the action of doxycycline toward with a 21-fold enhancement, while the corresponding 5-bromo-indole-3-carboxamide-PA3-7-3 analogue was able to enhance the action of both doxycycline and erythromycin toward and , respectively. The analogue was capable of disrupting the bacterial membrane of both and methicillin-resistant (MRSA) and the outer membrane of , suggesting that membrane perturbation could be a mechanism of action of both intrinsic antimicrobial activities and antibiotic potentiation.
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http://dx.doi.org/10.3390/biom14030261 | DOI Listing |
Int J STD AIDS
December 2024
New York State Department of Health AIDS Institute, Albany, NY, USA.
Background: Bacterial sexually transmitted infections (STIs) continue to increase in the United States. Despite evidence of the effectiveness of doxycycline post-exposure prophylaxis (Doxy-PEP) to prevent STIs, little is known about providers' attitudes and willingness to implement Doxy-PEP.
Methods: An online questionnaire was sent to 575 clinical providers in New York State in September 2022.
Mol Biol Cell
January 2025
Department of Biology, McGill University, Montréal, Québec H3A 1B1, Canada.
In neurons, patterns of different microtubule types are essential for neurite extension and nucleokinesis. Cellular model systems such as rodent primary cultures and induced pluripotent stem cells (iPSC)-derived neurons have provided key insights into how these patterns are created and maintained through the action of microtubule-associated proteins, motor proteins, and regulatory enzymes. iPSC-derived models show tremendous promise but lack benchmarking and validation relative to rodent primary cultures.
View Article and Find Full Text PDFAntibiotics (Basel)
October 2024
School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand.
In an effort to expand the spectrum of the antibacterial activity of pleuromutilin, a series of amine- and polyamine-linked analogues were prepared and evaluated for activities against a panel of microorganisms. Simple C-22-substituted amino esters or diamines , , , and , as well as two unusual amine-linked bis-pleuromutilin examples and , displayed variable levels of activity towards ATCC 25923 and methicillin-resistant , but with no detectable activities towards Gram-negative bacteria. Fortunately, the incorporation of a longer-chain triamine or polyamine (spermine) at C-22 did afford analogues (, ) that exhibited activity towards both ATCC 25923 and ATCC 25922 with MIC 6.
View Article and Find Full Text PDFDermatology
December 2024
Department of Dermatology, Incheon St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Animal
October 2024
Department of Biochemistry and Toxicology, University of Life Sciences, Akademicka 13, 20-950 Lublin, Poland.
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