Journal of Molecular Modeling

, Volume 15, Issue 4, pp 349–355

In-silico screening of new potential Bcl-2/Bcl-xl inhibitors as apoptosis modulators

Authors

    • Dipartimento Farmacochimico, Tossicologico e BiologicoUniversità degli Studi di Palermo
  • Marco Tutone
    • Dipartimento Farmacochimico, Tossicologico e BiologicoUniversità degli Studi di Palermo
  • Antonino Lauria
    • Dipartimento Farmacochimico, Tossicologico e BiologicoUniversità degli Studi di Palermo
Original Paper

DOI: 10.1007/s00894-008-0405-x

Cite this article as:
Almerico, A.M., Tutone, M. & Lauria, A. J Mol Model (2009) 15: 349. doi:10.1007/s00894-008-0405-x

Abstract

One of the major problems in the fight against cancer is drug-resistance, which, at a molecular level, can be acquired through mutations able to deactivate apoptosis. In particular, proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-xl and Bcl-2, are overexpressed in many tumours. The development of new inhibitors of these proteins as potential anticancer therapeutics represents a new frontier. In this work, we carried out an in-silico screening of compounds from a free database of more than 2 million structures (ZINC database), which allowed us to identify 17 sulfonamide derivatives as new potential inhibitors; these are currently undergoing biological evaluation.

Keywords

Apoptosis Bcl-2 Bcl-xl Inhibitors Molecular docking

Copyright information

© Springer-Verlag 2008