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Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure.

ABSTRACT: Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, three compounds from this series demonstrated up to a 30-fold higher brain/plasma ratio when compared to linezolid thereby indicating their therapeutic potential in brain associated disorders.

SUBMITTER: Seetharamsingh B

PROVIDER: S-EPMC4645245 | biostudies-other | 2015 Nov

REPOSITORIES: biostudies-other

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Design, Synthesis, and Identification of Silicon Incorporated Oxazolidinone Antibiotics with Improved Brain Exposure.

Seetharamsingh B B Ramesh Remya R Dange Santoshkumar S SS Khairnar Pankaj V PV Singhal Smita S Upadhyay Dilip D Veeraraghavan Sridhar S Viswanadha Srikant S Vakkalanka Swaroop S Reddy D Srinivasa DS

ACS medicinal chemistry letters 20151026 11

Therapeutic options for brain infections caused by pathogens with a reduced sensitivity to drugs are limited. Recent reports on the potential use of linezolid in treating brain infections prompted us to design novel compounds around this scaffold. Herein, we describe the design and synthesis of various oxazolidinone antibiotics with the incorporation of silicon. Our findings in preclinical species suggest that silicon incorporation is highly useful in improving brain exposures. Interestingly, th ...[more]

PMID: 26617962

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Silicon Incorporated Morpholine Antifungals: Design, Synthesis, and Biological Evaluation.

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2017-04-05 | GSE58404 | GEO

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Design, synthesis, and molecular docking of new phenothiazine incorporated <i>N</i>-Mannich bases as promising antimicrobial agents.

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