Facilely accessible multidrug resistance modulator derived from sucrose

Area of Science:

• Medicinal Chemistry
• Drug Discovery
• Carbohydrate Chemistry

Background:

• Multidrug resistance (MDR) is a major challenge in cancer therapy.
• P-glycoprotein (P-gp) is a key transporter involved in MDR.
• Novel MDR modulators are needed to improve treatment efficacy.

Purpose of the Study:

• To explore atractysucroses as scaffolds for novel MDR modulators.
• To synthesize and evaluate 2,3,4,3',4'-O-pentaisovalerylsucrose (compound 9) as a potential MDR modulator.

Main Methods:

• Sucrose derivatization to synthesize compound 9.
• Assessment of MDR modulating activity of compound 9 in vitro.
• Comparison of compound 9's activity with verapamil.

Main Results:

• Compound 9 was synthesized from sucrose in a three-step process with a 65% overall yield.
• Compound 9 demonstrated potent MDR modulating activity.
• Compound 9 exhibited superior MDR modulating activity compared to verapamil.

Conclusions:

• 2,3,4,3',4'-O-pentaisovalerylsucrose is a readily accessible and potent MDR modulator.
• Atractysucrose derivatives represent a promising scaffold for developing new MDR modulators.
• Compound 9 warrants further investigation as a potential therapeutic agent to overcome MDR.