title: Drug discovery targeting cell division proteins, microtubules and FtsZ.
abstract: Eukaryotic cell division or cytokinesis has been a major target for anticancer drug discovery. After the huge success of paclitaxel and docetaxel, microtubule-stabilizing agents (MSAs) appear to have gained a premier status in the discovery of next-generation anticancer agents. However, the drug resistance caused by MDR, point mutations, and overexpression of tubulin subtypes, etc., is a serious issue associated with these agents. Accordingly, the discovery and development of new-generation MSAs that can obviate various drug resistances has a significant meaning. In sharp contrast, prokaryotic cell division has been largely unexploited for the discovery and development of antibacterial drugs. However, recent studies on the mechanism of bacterial cytokinesis revealed that the most abundant and highly conserved cell division protein, FtsZ, would be an excellent new target for the drug discovery of next-generation antibacterial agents that can circumvent drug-resistances to the commonly used drugs for tuberculosis, MRSA and other infections. This review describes an account of our research on these two fronts in drug discovery, targeting eukaryotic as well as prokaryotic cell division.
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA; Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY 11794-3400, USA. Electronic address: iwao.ojima@stonybrook.edu.
authors.forename: Iwao
authors.initials: I
authors.lastname: Ojima
authors.affiliation: Institute of Chemical Biology & Drug Discovery, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Kunal
authors.initials: K
authors.lastname: Kumar
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Awasthi
authors.affiliation: Department of Chemistry, Stony Brook University, Stony Brook, NY 11794-3400, USA.
authors.forename: Jacob G
authors.initials: JG
authors.lastname: Vineberg
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D050257:Tubulin Modulators / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C071525:FtsZ protein, Bacteria; D050257:Tubulin Modulators
keywords: Antibacterial agent; Anticancer agent; Benzimidazole; Cytokinesis; FtsZ; Microtubule; Protofilament; Taxane; Taxoid; Tuberculosis; Tubulin