*5.2.2. Novel scaffolds*

**DRUG NAME**

298 Drug Discovery

BAL30376

PC190723

MUT7307

Nitazoxanide

Fidaxomicin

BPH652

Omiganan

TMC207 ATP synthase

Amikacin Novel drug delivery:

**Table 2.** New antibiotics in development

*5.2.1. Tailoring existing scaffolds*

TARGET/

Ceftobiprole Tight binding to PBP2a

Iclaprim Increased affinity

Rx100472 MethionyltRNA

MECHANISM OF ACTION

Ceftaroline Tight binding to PBP2a Gram-positive,

to bacterial DHFR

Monobactam/βlactamase inhibitor combination

Cell division protein FtsZ

Enoyl-ACP FabI reductase (fatty acid biosynthesis)

Inhibits vitamin cofactor of pyruvate:ferredoxin oxidoreductase (PFOR)

LED209 Quorum sensing S. typhimurium

Antimicrobial peptide; Depolarizes cytoplasmic membrane of bacteria

inhaled nanoliposomes

Virulence factor

SPECTRUM OF ACTIVITY

Gram-positive, Gram-negative

Gram-negative

Gram-positive, Gram-negative

Multi-drug resistant Gram-negative

Gram-positive,

synthetase inhibitor Gram-positive preclinical Trius Therapeutics

F. tularensis preclinical

inhibition M. tuberculosis Phase II Johnson & Johnson,

(antioxidant) MRSA preclinical University of

Gram-positive,

P. aeruginosa

It seems that there are many ways to search for new antibacterials, but the key question is: how to search for new antibacterial drugs and where to look for them? The most convenient method is to modify the existing scaffolds to generate their derivates. All antibiotics ap‐ proved between the early 1960s and 2000 were synthetic derivatives of the old scaffolds ex‐ cept carbapenems. Chemical modifications of old scaffolds may lead to improved bactericidal activities, better resistance profiles, safety, tolerability or superior pharmacoki‐

S. aureus preclinical Prolysis

Gram-negative preclinical Mutabilis

C. difficile Phase II Romark

fungi Phase III MIGENIX, Cadence

biofilm Phase II Transave Inc.

Sulopenem Binding to PBPs Gram-negative preclinical Pfizer

(OPT-80) Inhibits RNA synthesis C. difficile Phase II Optimer

CBR2092 Dual pharmacophore Gram-positive Phase I Cumbre

PHASE OF DEVELO-PMENT DRUG COMPANY OR INNOVATOR

Phase III Johnson & Johnson

Phase III Forrest Laboratories

Laboratories

Pharmaceuticals

Illinois, Chicago

pharmaceuticals

Tibotec

University of Texas South Western Medical Center,Dallas

Phase III Arpida

preclinical Basilea
