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

J Mol Model. 2009 Apr;15(4):349-55. doi: 10.1007/s00894-008-0405-x. Epub 2008 Dec 6.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Apoptosis*
  • Databases, Factual
  • Drug Resistance, Neoplasm*
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular*
  • Neoplasms / drug therapy*
  • bcl-X Protein / antagonists & inhibitors*

Substances

  • Antineoplastic Agents
  • BCL2L1 protein, human
  • bcl-X Protein