Anti-nitric oxide production activity of isothiocyanates correlates with their polar surface area rather than their lipophilicity

Toshiro Noshita, Yumi Kidachi, Hirokazu Funayama, Hiromasa Kiyota, Hideaki Yamaguchi, Kazuo Ryoyama

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

There is increasing demand for novel anti-inflammatory drugs with different mechanisms of action. We synthesized a series of isothiocyanates 2b-h based on 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) found in the pungent spice Wasabia japonica. Inhibitory activities against in-vitro growth of tumor cells and production of nitric oxide (NO) using the mouse macrophage-like cell line J774.1 were noted. All isothiocyanates were optimized by Hartree-Fock/3-21G model, and the log P values and the polar surface area (PSA) values were calculated. Substitution of the methylsulfinyl group (CH3S({double bond, long}O)-R) in 6-MITC with a formyl (CHO-R), a methylsulfanyl (CH2S-R) or a methyl (CH3-R) group reduced the activities of the parent isothiocyanate. Substitution with a formyl group resulted in lower lipophilicity (log P value) whereas substitution with a methylsulfanyl or methyl group resulted in a lower PSA value. The inhibitory activity of isothiocyanates showed better correlation with their PSA values rather than their partition coefficient (log P) values. Isothiocyanates with higher PSA values and some degree of log P value may have potent biological activity.

Original languageEnglish
Pages (from-to)4931-4936
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number12
DOIs
Publication statusPublished - Dec 1 2009
Externally publishedYes

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Keywords

  • Isothiocyanates
  • Nitric oxide
  • Polar surface area
  • Structure-activity relationship
  • Wasabi

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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