Polyene multi-drug resistance reversal agents.
The total synthesis of the polyene (-)-stipiamide has enabled the design and synthesis of new multi-drug resistance (MDR) reversal agents. MDR is a common clinical condition caused by overexpression of P-glycoprotein (P-gp), a transport protein that can dramatically lower the cellular concentration of antitumor drugs. Various non-toxic, truncated 6,7-acetylene analogs of stipiamide have been synthesized individually and in solution-phase libraries, and as a result potent compounds have been identified for MDR reversal, and P-gp-binding and inhibition. Potency and P-gp inhibition have also been explored using polyethylene glycol-linked polyene homodimers.
Andrus
Merritt B
MB
Brigham Young University, Department of Chemistry and Biochemistry, Provo, UT 84602, USA. mbandrus@chem.byu.edu
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D011090:Polyenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000900:Anti-Bacterial Agents; D011090:Polyenes; C069644:stipiamide