title: In-silico screening of new potential Bcl-2/Bcl-xl inhibitors as apoptosis modulators.
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.
authors.affiliation: Dipartimento Farmacochimico, Tossicologico e Biologico, Università degli Studi di Palermo, Via Archirafi 32, 90123, Palermo, Italy. almerico@unipa.it
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Almerico
authors.forename: Marco
authors.initials: M
authors.lastname: Tutone
authors.forename: Antonino
authors.initials: A
authors.lastname: Lauria
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D017209:Apoptosis; D016208:Databases, Factual; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy*; D051020:bcl-X Protein / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D051020:bcl-X Protein