Synthesis, formulation and in vitro evaluation of a novel microtubule destabilizer, SMART-100

Feng Li, Yan Lu, Wei Li, Duane Miller, Ram I. Mahato

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

A novel microtubule destabilizer, substituted methoxybenzoyl-ary-thiazole (SMART)-100, was synthesized, which showed good anticancer activity in HepG2 cells. SMART-100 was able to circumvent multidrug resistance (MDR) and effectively inhibited the growth of cell lines that overexpress P-glycoprotein (P-gp). SMART-100 inhibited P-gp activity, which may be responsible for its ability to overcome MDR. Since SMART-100 is poorly soluble in water, it was formulated in polyethylene-b-poly(d,l-lactide) (PEG-PLA) micelles. The solubility of SMART-100 was increased by more than 1.1×105 folds. SMART-100 loaded PEG-PLA micelles could effectively inhibit HepG2 cell growth and arrest cell cycle progression at G2/M phase, followed by appearance of a sub-G1 phase, which is indicative of cell apoptosis. Increased Caspase-3 activity was also observed when HepG2 cells were treated with SMART-100. The anticancer activity of SMART-100 loaded PEG-PLA micelles was also evaluated on luciferase expressing C4-2-Luc cell lines by IVIS imaging. Our results suggest that SMART-100 has the potential to treat resistant cancers.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalJournal of Controlled Release
Volume143
Issue number1
DOIs
StatePublished - Apr 1 2010

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Thiazoles
Microtubules
Hep G2 Cells
Micelles
Multiple Drug Resistance
P-Glycoprotein
In Vitro Techniques
Cell Line
G2 Phase
G1 Phase
Polyethylene
Growth
Cell Cycle Checkpoints
Luciferases
Caspase 3
Cell Division
Solubility
Apoptosis

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Synthesis, formulation and in vitro evaluation of a novel microtubule destabilizer, SMART-100. / Li, Feng; Lu, Yan; Li, Wei; Miller, Duane; Mahato, Ram I.

In: Journal of Controlled Release, Vol. 143, No. 1, 01.04.2010, p. 151-158.

Research output: Contribution to journalArticle

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