# NEW ANTIBIOTICS--ISOLATION, SYNTHESIS, AND EVALUATION

> **NIH NIH R01** · UNIVERSITY OF KANSAS LAWRENCE · 1993 · $206,573

## Abstract

The goal of this research is to study the antiinfective agents present in
unusual sources, notably higher plant extracts (and of molecules inspired
by them), in order to discover new chemical entities with novel modes of
action and to determine their potential for use in human medicine. Novel
antibiotics are specially sought for the treatment of troublesome viral
infections against which contemporary antibiotics are not fully
satisfactory because of toxicity, low potency, narrow spectrum,
resistance, poor pharmacokinetics, or the like. Central to this effort is
the exploration of extracts of suitable botanically identified plants
(including those with a folkloric reputation for use as antiinfectives),
extraction, screening in vitro against HIV and BIV viruses, bioassay
directed fractionation, physico-chemical structure determination,
synthesis of analogs (where indicated for structural clarification,
preparation of substantial quantities for evaluation, optimization of
activity, etc.), evaluation of in vitro antiinfective spectrum in
comparison with established agents, and in vivo evaluation in infected
experimental animals for the most likely candidates. The latter is done
off-site by pharmaceutical firms possessing the special facilities and
expertise for this work.

Investigation of the molecular mode of action of the quinolones and their
interaction with DNA and DNAgyrase was notably successful in earlier
versions of this application and these studies will be continued. The
fluoroquinolones are among the most widely investigated contemporary
antibiotics. Six are marketed in the US, another dozen are approaching
marketing decisions and many more are less advanced. One of the quinolones
prepared in an earlier version of this grant (levoxacin) is notably active
against bacteria causing death to HIV sufferers and is under clinical
trial in Japan and the US. We have elaborated and are testing successfully
a theory of the molecular mode of action of these agents and this theory
is guiding successful design of new chemical entities. Further examination
of this theory is proposed as is extension to possible application against
the fungal and mammalian enzymes so as to extend or shift the spectrum of
contemporary quinolones to include other organisms dangerous to HIV
sufferers and to the treatment of cancer. Alternative proposals to
rationalize the molecular mode of action of quinolones are also under
investigation. Attempts to broaden these investigations to mammalian DNA
topoisomerase II are also in progress.

The need for modern screening activity is particularly pressing as
pressure on tropical biota, alternate land use schemes, and other societal
changes in the Third World countries make tropical species and indigenous
medical systems increasingly vulnerable.

## Key facts

- **NIH application ID:** 3125403
- **Project number:** 2R01AI013155-17A3
- **Recipient organization:** UNIVERSITY OF KANSAS LAWRENCE
- **SAM.gov UEI:** SSUJB3GSH8A5
- **Principal Investigator:** Lester A. Mitscher
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $206,573
- **Award type:** 2
- **Project period:** 1976-09-01 → 1997-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3125403

## Citation

> US National Institutes of Health, RePORTER application 3125403, NEW ANTIBIOTICS--ISOLATION, SYNTHESIS, AND EVALUATION (2R01AI013155-17A3). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3125403. Licensed CC0.

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