Pharmacophore mapping and virtual screening for SIRT1 activators

Sugunadevi Sakkiah, Navaneethakrishnan Krishnamoorthy, Poornima Gajendrarao, Sundarapandian Thangapandian, Yuno Lee, Songmi Kim, Jung Keun Suh, Hyong Ha Kim, Keun Woo Lee

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Silent information regulator 2 (Sir2) or sirtuins are NAD(+)-dependent deacetylases, which hydrolyze the acetyllysine residues. In mammals, sirtuins are classified into seven different classes (SIRT1-7). SIRT1 was reported to be involved in age related disorders like obesity, metabolic syndrome, type II diabetes mellitus and Parkinson's disease. Activation of SIRT1 is one of the promising approaches to treat these age related diseases. In this study, we have used HipHop module of CATALYST to identify a series of pharmacophore models to screen SIRT1 enhancing molecules. Three molecules from Sirtris Pharmaceuticals were selected as training set and 607 sirtuin activator molecules were used as test set. Five different hypotheses were developed and then validated using the training set and the test set. The results showed that the best pharmacophore model has four features, ring aromatic, positive ionization and two hydrogen-bond acceptors. The best hypothesis from our study, Hypo2, screened high number of active molecules from the test set. Thus, we suggest that this four feature pharmacophore model could be helpful to screen novel SIRT1 activator molecules. Hypo2-virtual screening against Maybridge database reveals seven molecules, which contains all the critical features. Moreover, two new scaffolds were identified from this study. These scaffolds may be a potent lead for the SIRT1 activation.

Original languageEnglish
Pages (from-to)1152-1156
Number of pages5
JournalBulletin of the Korean Chemical Society
Volume30
Issue number5
DOIs
Publication statusPublished - 13 Oct 2009
Externally publishedYes

Fingerprint

Screening
Molecules
Sirtuins
Scaffolds
Chemical activation
Mammals
Medical problems
NAD
Ionization
Hydrogen bonds
Pharmaceutical Preparations

Keywords

  • HipHop
  • Pharmacophore
  • SIRT1
  • Sirtuin
  • Sirtuin activator

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Sakkiah, S., Krishnamoorthy, N., Gajendrarao, P., Thangapandian, S., Lee, Y., Kim, S., ... Lee, K. W. (2009). Pharmacophore mapping and virtual screening for SIRT1 activators. Bulletin of the Korean Chemical Society, 30(5), 1152-1156. https://doi.org/10.5012/bkcs.2009.30.5.1152

Pharmacophore mapping and virtual screening for SIRT1 activators. / Sakkiah, Sugunadevi; Krishnamoorthy, Navaneethakrishnan; Gajendrarao, Poornima; Thangapandian, Sundarapandian; Lee, Yuno; Kim, Songmi; Suh, Jung Keun; Kim, Hyong Ha; Lee, Keun Woo.

In: Bulletin of the Korean Chemical Society, Vol. 30, No. 5, 13.10.2009, p. 1152-1156.

Research output: Contribution to journalArticle

Sakkiah, S, Krishnamoorthy, N, Gajendrarao, P, Thangapandian, S, Lee, Y, Kim, S, Suh, JK, Kim, HH & Lee, KW 2009, 'Pharmacophore mapping and virtual screening for SIRT1 activators', Bulletin of the Korean Chemical Society, vol. 30, no. 5, pp. 1152-1156. https://doi.org/10.5012/bkcs.2009.30.5.1152
Sakkiah, Sugunadevi ; Krishnamoorthy, Navaneethakrishnan ; Gajendrarao, Poornima ; Thangapandian, Sundarapandian ; Lee, Yuno ; Kim, Songmi ; Suh, Jung Keun ; Kim, Hyong Ha ; Lee, Keun Woo. / Pharmacophore mapping and virtual screening for SIRT1 activators. In: Bulletin of the Korean Chemical Society. 2009 ; Vol. 30, No. 5. pp. 1152-1156.
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