HTS, chemical hybridization, and drug design identify a chemically unique antituberculosis agent-coupling serendipity and rational approaches to drug discovery

Jialin Mao, Baojie Wan, Yuehong Wang, Scott G. Franzblau, Alan P. Kozikowski

Research output: Contribution to journalArticle

Abstract

The high throughput screening of two chemical libraries against Mycobacterium tuberculosis led to the design of hybrid compounds by using nitrile oxide cycloaddition chemistry. One of the hybrids shows an excellent MIC against M. tuberculosis H37Rv. As this molecule shows no CYP3A4 inhibition and a maximum tolerated dose of ≥200 mgkg-1 po in mice, it represents a potential drug candidate for TB therapy. (Chemical Equation Presented)

Original languageEnglish (US)
Pages (from-to)811-813
Number of pages3
JournalChemMedChem
Volume2
Issue number6
DOIs
StatePublished - Jun 11 2007
Externally publishedYes

Fingerprint

Cytochrome P-450 CYP3A
Nitriles
Cycloaddition
Drug Design
Coupling agents
Drug Discovery
Mycobacterium tuberculosis
Oxides
Screening
Throughput
Small Molecule Libraries
Molecules
Maximum Tolerated Dose
Cycloaddition Reaction
Pharmaceutical Preparations
Therapeutics

Keywords

  • Isoxazole
  • Mefloquine
  • MIC
  • Nitrile oxide cycloaddition
  • Tuberculosis

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

Cite this

HTS, chemical hybridization, and drug design identify a chemically unique antituberculosis agent-coupling serendipity and rational approaches to drug discovery. / Mao, Jialin; Wan, Baojie; Wang, Yuehong; Franzblau, Scott G.; Kozikowski, Alan P.

In: ChemMedChem, Vol. 2, No. 6, 11.06.2007, p. 811-813.

Research output: Contribution to journalArticle

Mao, Jialin ; Wan, Baojie ; Wang, Yuehong ; Franzblau, Scott G. ; Kozikowski, Alan P. / HTS, chemical hybridization, and drug design identify a chemically unique antituberculosis agent-coupling serendipity and rational approaches to drug discovery. In: ChemMedChem. 2007 ; Vol. 2, No. 6. pp. 811-813.
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