New taxanes as highly efficient reversal agents for multi-drug resistance in cancer cells

Ojima, Iwao; Bounaud, Pierre‐Yves; Takeuchi, Craig S.; Pera, Paula; Bernacki, Ralph J.

doi:10.1016/s0960-894x(97)10218-9

Cited by 55 publications

(37 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the anticancer drug warhead, we used a highly potent 2 nd -generation taxoid, SB-T-1214. [ Note: 2nd-generation taxoids exhibit 2-3 orders of magnitude higher potency against multidrug-resistant (MDR) cancer cell lines as compared with paclitaxel (Taxol ® ), which is the most widely used anticancer drug in current chemotherapy treatments 78,79…”

Section: Resultsmentioning

confidence: 99%

Functionalized Single-Walled Carbon Nanotubes as Rationally Designed Vehicles for Tumor-Targeted Drug Delivery

et al. 2008

Self Cite

View full text Add to dashboard Cite

A novel single-walled carbon nanotube (SWNT)-based tumor-targeted drug delivery system (DDS) has been developed, which consists of a functionalized SWNT linked to tumor-targeting modules as well as prodrug modules. There are three key features of this nanoscale DDS: (a) use of functionalized SWNTs as a biocompatible platform for the delivery of therapeutic drugs or diagnostics, (b) conjugation of prodrug modules of an anticancer agent (taxoid with a cleavable linker) that is activated to its cytotoxic form inside the tumor cells upon internalization and in situ drug release, and (c) attachment of tumor-recognition modules (biotin and a spacer) to the nanotube surface. To prove the efficacy of this DDS, three fluorescent and fluorogenic molecular probes were designed, synthesized, characterized and subjected to the analysis of the receptor-mediated endocytosis and drug release inside the cancer cells (L1210FR leukemia cell line) by means of confocal fluorescence microscopy. The specificity and cytotoxicity of the conjugate have also been assessed and compared with L1210 and human non-cancerous cell lines. Then, it has unambiguously been proven that this tumor-targeting DDS works exactly as designed and shows high potency towards specific cancer cell lines, thereby forming a solid foundation for further development.

show abstract

Section: Resultsmentioning

confidence: 99%

Functionalized Single-Walled Carbon Nanotubes as Rationally Designed Vehicles for Tumor-Targeted Drug Delivery

et al. 2008

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following the hypothesis that compounds that affect tubulin/microtubule would serve as leads for developing FtsZ inhibitors, a library of taxanes was screened for antibacterial activity against Mtb cells. 127 Real time PCR-based assay was employed to screen cytotoxic taxanes that stabilize microtubules 135–137 as well as non-cytotoxic taxane-multidrug resistance reversal agents (TRAs) 138–144 that inhibit the efflux pumps of ATP-binding cassette (ABC) transporters such as P-glycoprotein (P-gp).…”

Section: Ftsz and Antibacterial Agentsmentioning

confidence: 99%

Drug discovery targeting cell division proteins, microtubules and FtsZ

Ojima

Kumar

Awasthi

et al. 2014

Bioorganic & Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Following the hypothesis that compounds that affect tubulin/microtubule would serve as leads for developing FtsZ inhibitors [44–46], a library of taxanes was designed and screened for antibacterial activity against Mtb cells. A real-time PCR-based assay was employed to screen taxanes, such as cytotoxic taxoids that stabilize microtubules [48–50] and noncytotoxic taxane-MDR reversal agents [51–58] that inhibit the efflux pumps of ATP-binding cassette transporters such as P-glycoprotein. Of the 120 taxanes screened, several compounds exhibited significant anti-TB activity [59].…”

Section: Mtb Ftsz Inhibitorsmentioning

confidence: 99%

Discovery of Anti-TB Agents that Target the Cell-Division Protein FtsZ

et al. 2010

Self Cite

View full text Add to dashboard Cite

The emergence of multidrug-resistant Mycobacterium tuberculosis strains has made many of the currently available anti-tuberculosis (TB) drugs ineffective. Accordingly, there is a pressing need to identify new drug targets. Filamentous temperature-sensitive protein Z (FtsZ), a bacterial tubulin homologue, is an essential cell-division protein that polymerizes in a GTP-dependent manner, forming a highly dynamic cytokinetic ring, designated as the Z ring, at the septum site. Other cell-division proteins are recruited to the Z ring and, upon resolution of the septum, two daughter cells are produced. Since inactivation of FtsZ or alteration of FtsZ assembly results in the inhibition of Z-ring and septum formation, FtsZ is a very promising target for novel antimicrobial drug development. This review describes the function and dynamic behaviors of FtsZ and the recent development of FtsZ inhibitors as potential anti-TB agents.

show abstract

New taxanes as highly efficient reversal agents for multi-drug resistance in cancer cells

Cited by 55 publications

References 9 publications

Functionalized Single-Walled Carbon Nanotubes as Rationally Designed Vehicles for Tumor-Targeted Drug Delivery

Functionalized Single-Walled Carbon Nanotubes as Rationally Designed Vehicles for Tumor-Targeted Drug Delivery

Drug discovery targeting cell division proteins, microtubules and FtsZ

Discovery of Anti-TB Agents that Target the Cell-Division Protein FtsZ

Contact Info

Product

Resources

About