# Discovery through chemical synthesis of antibiotics effective against modern bacterial pathogens

> **NIH NIH R01** · HARVARD UNIVERSITY · 2022 · $766,682

## Abstract

PROJECT SUMMARY/ABSTRACT
In recent decades, the emergence of antibiotic resistance in bacteria has greatly outpaced the discovery of novel
antibacterial agents. This research is focused on the synthesis and biological study of antibiotics effective against
these modern pathogens of urgent threat. To this end, the lincosamides have been identified as an
underexploited class of antibiotics. No new lincosamide has entered the market since clindamycin was approved
more than 50 years ago (FDA, 1970). Growing resistance to clindamycin and its propensity to induce life-
threatening Clostridioides difficile (C. difficile) colitis have limited its utility in today’s armamentarium. Due to the
structural complexity of this class of natural products, semi-synthetic strategies are insufficient to support future
antibiotic drug discovery within this or related scaffolds. Here, efficient synthetic pathways will be developed and
implemented to prepare a large collection of lincosamide analogs inaccessible by any other means. These
include analogs of a lead candidate, iboxamycin, which features a novel bicyclic oxepanoprolinamide scaffold
and is efficacious in vitro and in vivo against a broad range of multi-drug resistant (MDR) bacteria. The latter
include MDR ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae,
Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.), identified by the WHO as targets
of highest priority in antibiotic development. By elucidating the mechanistic underpinnings and drivers of in vivo
efficacy of iboxamycin and future lead antibiotics, this research will deliver multiple novel antibiotic scaffolds for
preclinical exploration to target these challenging pathogens.

## Key facts

- **NIH application ID:** 10419458
- **Project number:** 1R01AI168228-01
- **Recipient organization:** HARVARD UNIVERSITY
- **Principal Investigator:** ANDREW G MYERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $766,682
- **Award type:** 1
- **Project period:** 2022-02-10 → 2027-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10419458

## Citation

> US National Institutes of Health, RePORTER application 10419458, Discovery through chemical synthesis of antibiotics effective against modern bacterial pathogens (1R01AI168228-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10419458. Licensed CC0.

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